50 CFR 660.320 - Open access fishery-crossover provisions.

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2010-10-01

... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Open access fishery-crossover provisions... West Coast Groundfish-Open Access Fisheries § 660.320 Open access fishery—crossover provisions. (a) Operating in both limited entry and open access fisheries. See provisions at § 660.60, subpart C. (b...

Pharmacokinetic interaction of finasteride with tamsulosin hydrochloride: an open-label, randomized, 3-period crossover study in healthy Chinese male volunteers.

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Chu, Nannan; Xu, Hongrong; Wang, Guoqin; Wang, Jiangdian; Chen, Weili; Yuan, Fei; Yang, Mengjie; Li, Xuening

2015-02-01

The primary aim of this study was to evaluate whether there was clinically significant pharmacokinetic (PK) interaction between finasteride and tamsulosin in healthy Chinese male subjects. This was an open-label, randomized, 3-period, crossover study. Subjects received single and multiple doses of 5 mg finasteride alone, single and multiple doses of 0.2 mg tamsulosin hydrochloride sustained-release capsule alone, and single and multiple doses of 5 mg finasteride with 0.2 mg tamsulosin hydrochloride, in an order determined by a computerized randomization schedule. Blood samples were collected up to 48 hours after dosing on study day 1 and up to 24 hours after dosing on study day 9 for determination of plasma concentrations with a validated LC-MS/MS method. Pharmacokinetic parameters were estimated via noncompartmental methods. Tolerability was evaluated by monitoring adverse events, laboratory assays, vital signs, and 12-lead ECG. Fifteen subjects were enrolled, and 14 completed the study. The geometric mean ratios (GMRs) (90% CIs) of AUC(τ,ss) and C(max,ss) values of finasteride at steady state between coadministration of finasteride and tamsulosin hydrochloride and finasteride alone were 1.14 (1.05-1.23) and 1.06 (0.99-1.14), respectively. The GMRs (90% CIs) for AUC(0-t) and C(max) values of finasteride for a single dose of coadministration of finasteride and tamsulosin hydrochloride and finasteride alone were 1.02 (0.94-1.11) and 1.06 (1.01-1.11), respectively. The GMRs (90% CIs) for AUC(τ,ss) and C(max,ss) values of tamsulosin at steady-state for coadministration of finasteride and tamsulosin hydrochloride and tamsulosin hydrochloride alone were 1.18 (1.05-1.33) and 1.23 (1.06-1.43), respectively. The GMRs (90% CIs) for AUC(0-t) and C(max) values of tamsulosin for a single dose of coadministration of finasteride and tamsulosin hydrochloride and tamsulosin hydrochloride alone were 1.04 (0.97-1.10) and 1.04 (0.98-1.11), respectively. Statistical analyses

Intra-ocular pressure-lowering effects of a Rho kinase inhibitor, ripasudil (K-115), over 24 hours in primary open-angle glaucoma and ocular hypertension: a randomized, open-label, crossover study.

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Tanihara, Hidenobu; Inoue, Toshihiro; Yamamoto, Tetsuya; Kuwayama, Yasuaki; Abe, Haruki; Suganami, Hideki; Araie, Makoto

2015-06-01

To investigate the intra-ocular pressure (IOP)-lowering effects of a selective Rho kinase inhibitor, ripasudil (K-115), over 24 hr in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). In this multicenter, prospective, randomized, open-label, 3-period, Latin-square crossover clinical study, 28 patients with POAG or OHT whose IOP level was 21 mmHg or higher were subdivided into three groups. Each patient was treated with placebo and ripasudil in concentrations of 0.2 and 0.4%, at 9:00 and 21:00 on day 1 through a total of 3 periods separated by washout periods. IOP was measured at 9:00, 10:00, 11:00, 13:00, 16:00, 19:00, 21:00, 22:00 and 23:00 on day 1, and 1:00, 4:00, 7:00 and 9:00 on day 2 in sitting position using Goldmann applanation tonometer. Main outcome measure was the IOP reduction of placebo and ripasudil from baseline. The mean IOP reduction was -5.2 mmHg for 0.2%, -6.4 mmHg for 0.4% and -2.0 mmHg for placebo at 2 hr after the first instillation. Also, the corresponding values were -6.8 mmHg for 0.2%, -7.3 mmHg for 0.4% and -4.1 mmHg for placebo at 2 hr after the second instillation. Statistically significant IOP reduction, compared with placebo, was found for both 0.2 and 0.4% from 1 through 7 hr after each instillation. In safety, conjunctival hyperaemia was observed in 22 patients (79%) for 0.2%, 27 patients (96%) for 0.4% and three patients (11%) for placebo. Ripasudil is a promising new topical medication to lower IOP for at least 7 hr after instillations in patients with POAG or OHT. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

LDL-cholesterol lowering effect of a new dietary supplement: an open label, controlled, randomized, cross-over clinical trial in patients with mild-to-moderate hypercholesterolemia.

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Magno, S; Ceccarini, G; Pelosini, C; Jaccheri, R; Vitti, J; Fierabracci, P; Salvetti, G; Airoldi, G; Minale, M; Saponati, G; Santini, F

2018-05-24

Hypercholesterolemia is a major risk factor for cardiovascular disorders and requires specific intervention through an adequate lifestyle (diet and physical exercise) and, if necessary, an appropriate drug treatment. Lipid-lowering drugs, although generally efficacious, may sometimes cause adverse events. A growing attention has been devoted to the correction of dyslipidemias through the use of dietary supplements. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K, L-arginine, coenzyme Q10 and ascorbic acid, named Argicolina (A), compared to a commercially available product containing monacolin K and coenzyme Q10, Normolip 5 (N). This was a single center, controlled, randomized, open-label, cross-over clinical study enrolling 20 Caucasian outpatients aged 18-75 years with serum LDL-C between 130 and 180 mg/dL. Patients assumed two different dietary supplements (A and N) both containing monacolin K 10 mg for 8 weeks each, separated by a 4-week wash-out period. Evaluated parameters were: Total cholesterol (Tot-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose, aspartate aminotransferase, alanine aminotransferase, creatinekinase, gamma-glutamyl-transpeptidase, brachial arterial pressure and heart rate, measured at the start and at the end of each treatment period. Safety was monitored through the study. LDL-C decreased by 23.3% during treatment with N (p ascorbic acid also produces a significant reduction of triglycerides without significant effects on HDL. ClinicalTrials.gov ID: NCT03425630 .

Pharmacokinetic interaction between udenafil and dapoxetine: a randomized, open-labeled crossover study in healthy male volunteers

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Kim YH

2015-02-01

Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Shi Hyang Lee,1 Hae Sun Jeon,1 Hyeong-Seok Lim,1 Mi Young Bahng,2 Kyun-Seop Bae1 1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, College of Medicine, University of Ulsan, 2Clinical Development Department, Dong-A ST Co, Ltd, Seoul, Republic of Korea Background: “Udenafil” is a phosphodiesterase-5 inhibitor indicated for erectile dysfunction. “Dapoxetine” is a serotonin transport inhibitor indicated for premature ejaculation. The aim of the study reported here was to investigate the pharmacokinetic drug interaction between udenafil and dapoxetine in healthy male subjects. Methods: An open-label, three-treatment, six-sequence, three-period crossover study was performed in healthy male subjects. In varying sequences, each subjects received single oral doses of udenafil 200 mg, dapoxetine 60 mg, and both treatments. The periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 hours after dosing. The plasma concentrations of udenafil and dapoxetine were determined using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by non-compartmental analysis. Tolerability was assessed throughout the study. Results: Twenty-three healthy subjects completed the study. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for udenafil were 0.923 (90% confidence interval [CI]: 0.863–0.987 and 0.864 (90% CI: 0.789–0.947, respectively. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for dapoxetine were 1.125 (90% CI: 1.044–1.213 and 0.837 (90% CI: 0.758–0.925, respectively. There were no serious adverse events reported, and none of the subjects dropped out due to adverse events

Comparative bioavailability and pharmacokinetics of two oral formulations of flurbiprofen: a single-dose, randomized, open-label, two-period, crossover study in Pakistani subjects.

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Qayyum, Aisha; Najmi, Muzammil Hasan; Abbas, Mateen

2013-11-01

Comparative bioavailability studies are conducted to establish the bioequivalence of generic formulation with that of branded reference formulation, providing confidence to clinicians to use these products interchangeably. This study was carried out to compare a locally manufactured formulation of flurbiprofen with that of a branded product. Twenty two healthy male adults received a single dose of flurbiprofen (100mg) either generic or branded product according to randomization scheme on each of 2 periods. Blood samples were collected and plasma flurbiprofen concentration was determined by a validated HPLC method. Pharmacokinetic parameters like AUC(0-t), AUC(0-oo), Cmax, Tmax, t½, Vd and clearance were determined. The 90% CI for the ratio of geometric means of test to reference product's pharmacokinetic variables was calculated. Pharmacokinetic parameters for two formulations were comparable. Ratio of means of AUC(0-24), AUC(0-oo) and Cmax for test to reference products and 90% CI for these ratios were within the acceptable range. The p-values calculated by TOST were much less than the specified value (p-0.05). ANOVA gave p-values which were more than the specified value (p-0.05) for sequence, subject, period and formulation. Test formulation of flurbiprofen (tablet Flurso) was found to meet the criteria for bioequivalence to branded product (tablet Ansaid) based on pharmacokinetic parameters.

Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

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Diaz, Francisco J; Berg, Michel J; Krebill, Ron; Welty, Timothy; Gidal, Barry E; Alloway, Rita; Privitera, Michael

2013-12-01

Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.

EffenDys-Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Patients With Advanced Cancer: A Multicenter, Open-Label, Randomized, Morphine-Controlled, Crossover, Phase II Trial.

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Simon, Steffen T; Kloke, Marianne; Alt-Epping, Bernd; Gärtner, Jan; Hellmich, Martin; Hein, Rebecca; Piel, Maren; Cornely, Oliver A; Nauck, Friedemann; Voltz, Raymond

2016-11-01

Episodic breathlessness is a frequent and burdensome symptom in cancer patients but pharmacological treatment is limited. To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl in comparison to immediate-release morphine for the relief of episodic breathlessness. Phase II, investigator-initiated, multicenter, open-label, randomized, morphine-controlled, crossover trial with open-label titration of fentanyl buccal tablet (FBT) in inpatients with incurable cancer. The primary outcome was time to onset of meaningful breathlessness relief. Secondary outcomes were efficacy (breathlessness intensity difference at 10 and 30 minutes; sum of breathlessness intensity difference at 15 and 60 minutes), feasibility, and safety. Study was approved by local ethics committees. Twenty-five of 1341 patients were eligible, 10 patients agreed to participate (four female, mean age 58 ± 11, mean Karnofsky score 67 ± 11). Two patients died before final visits and two patients dropped-out because of disease progression leaving six patients for analysis with 61 episodes of breathlessness. Mean time to onset was for FBT 12.7 ± 10.0 and for immediate-release morphine 23.6 ± 15.1 minutes with a mean difference of -10.9 minutes (95% CI = -24.5 to 2.7, P = 0.094). Efficacy measures were predominately in favor for FBT. Both interventions were safe. Feasibility failed because of too much study demands for a very ill patient group. The description of a faster and greater relief of episodic breathlessness by transmucosal fentanyl versus morphine justifies further evaluation by a full-powered trial. Copyright © 2016. Published by Elsevier Inc.

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period.

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Kadowaki, Takashi; Kondo, Kazuoki; Sasaki, Noriyuki; Miyayama, Kyoko; Yokota, Shoko; Terata, Ryuji; Gouda, Maki

2017-09-01

To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was -0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P 1). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. NCT02081599.

Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

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Helmy, Sally A; El-Bedaiwy, Heba M

2014-11-01

Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated. © 2014, The American College of Clinical Pharmacology.

An exploratory, randomized, parallel-group, open-label, relative bioavailability study with an additional two-period crossover food-effect study exploring the pharmacokinetics of two novel formulations of pexmetinib (ARRY-614

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Wollenberg LA

2015-09-01

Full Text Available Lance A Wollenberg,1 Donald T Corson,2,3 Courtney A Nugent,1 Farran L Peterson,1 Ann M Ptaszynski,1 Alisha Arrigo,2,3 Coralee G Mannila,2,3 Kevin S Litwiler,1 Stacie J Bell1,4 1Array BioPharma, Boulder, 2Array BioPharma, Longmont, CO, 3Avista Pharma Solutions, Longmont, CO, 4Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA Background: Pexmetinib (ARRY-614 is a dual inhibitor of p38 mitogen-activated protein kinase and Tie2 signaling pathways implicated in the pathogenesis of myelodysplastic syndromes. Previous clinical experience in a Phase I dose-escalation study of myelodysplastic syndrome patients using pexmetinib administered as neat powder-in-capsule (PIC exhibited high variability in pharmacokinetics and excessive pill burden, prompting an effort to improve the formulation of pexmetinib. Methods: A relative bioavailability assessment encompassed three parallel treatment cohorts of unique subjects comparing the two new formulations (12 subjects per cohort, a liquid oral suspension (LOS and liquid-filled capsule (LFC and the current clinical PIC formulation (six subjects in a fasted state. The food-effect assessment was conducted as a crossover of the LOS and LFC formulations administered under fed and fasted conditions. Subjects were divided into two groups of equal size to evaluate potential period effects on the food-effect assessment. Results: The geometric mean values of the total plasma exposures based upon area-under-the-curve to the last quantifiable sample (AUClast of pexmetinib were approximately four- and twofold higher after administration of the LFC and LOS formulations, respectively, than after the PIC formulation, when the formulations were administered in the fasted state. When the LFC formulation was administered in the fed state, pexmetinib AUClast decreased by <5% compared with the fasted state. After administration of the LOS formulation in the fed state, pexmetinib AUClast was 34% greater than observed in the fasted

Self-Administered Computer Therapy for Apraxia of Speech: Two-Period Randomized Control Trial With Crossover.

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Varley, Rosemary; Cowell, Patricia E; Dyson, Lucy; Inglis, Lesley; Roper, Abigail; Whiteside, Sandra P

2016-03-01

There is currently little evidence on effective interventions for poststroke apraxia of speech. We report outcomes of a trial of self-administered computer therapy for apraxia of speech. Effects of speech intervention on naming and repetition of treated and untreated words were compared with those of a visuospatial sham program. The study used a parallel-group, 2-period, crossover design, with participants receiving 2 interventions. Fifty participants with chronic and stable apraxia of speech were randomly allocated to 1 of 2 order conditions: speech-first condition versus sham-first condition. Period 1 design was equivalent to a randomized controlled trial. We report results for this period and profile the effect of the period 2 crossover. Period 1 results revealed significant improvement in naming and repetition only in the speech-first group. The sham-first group displayed improvement in speech production after speech intervention in period 2. Significant improvement of treated words was found in both naming and repetition, with little generalization to structurally similar and dissimilar untreated words. Speech gains were largely maintained after withdrawal of intervention. There was a significant relationship between treatment dose and response. However, average self-administered dose was modest for both groups. Future software design would benefit from incorporation of social and gaming components to boost motivation. Single-word production can be improved in chronic apraxia of speech with behavioral intervention. Self-administered computerized therapy is a promising method for delivering high-intensity speech/language rehabilitation. URL: http://orcid.org/0000-0002-1278-0601. Unique identifier: ISRCTN88245643. © 2016 American Heart Association, Inc.

Open-Label Single-Sequence Crossover Study Evaluating Pharmacokinetics, Efficacy, and Safety of Once-Daily Dosing of Nitisinone in Patients with Hereditary Tyrosinemia Type 1.

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Guffon, Nathalie; Bröijersén, Anders; Palmgren, Ingrid; Rudebeck, Mattias; Olsson, Birgitta

2018-01-01

Although nitisinone is successfully used to treat hereditary tyrosinemia type 1 (HT-1) with the recommended twice-daily dosing, data describing a long half-life motivate less frequent dosing. Therefore, in agreement with the Pharmacovigilance Risk Assessment Committee at the European Medicines Agency, this study was performed to investigate the switch to once-daily dosing. This open-label, non-randomized, single-sequence crossover study evaluated the pharmacokinetics, efficacy, and safety of once-daily compared to twice-daily dosing of nitisinone in patients with HT-1 (NCT02323529). Well-controlled patients of dry blood spots by tandem mass spectrometry. The primary endpoint was C min of nitisinone after ≥4 weeks of treatment on each dosing regimen. Secondary objectives were evaluation of efficacy and safety during each dosing regimen. In total, 19 patients were enrolled and 17 included in the per-protocol analysis set. The mean (SD) nitisinone C min decreased by 23%, from 26.4 (10.2) to 21.2 (9.9) μmol/L in dry blood spot samples (not equivalent to plasma concentrations), when patients switched from twice- to once-daily dosing. There was no apparent age- or bodyweight-related trend in the degree of C min decrease. No patient had quantifiable succinylacetone levels during the once-daily treatment period, indicating efficacious treatment. All adverse events were mild or moderate and judged unrelated to nitisinone. The switch to once-daily treatment with nitisinone appeared efficacious and safe in the treatment of patients with HT-1.

The Lack of Effect of Food on the Pharmacokinetics of ZX008 (Fenfluramine Oral Solution): Results of a Single-dose, Two-period Crossover Study.

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Gammaitoni, Arnold; Smith, Steven; Boyd, Brooks

2018-06-22

Fenfluramine is being developed as a low-dose adjunctive treatment for seizures in patients with Dravet syndrome and other epileptic encephalopathies, including Lennox-Gastaut syndrome. Most patients with Dravet syndrome receive multiple antiepileptic drugs, making it challenging for caregivers to track correct administration times. The present Phase I study was conducted to determine the effect of food on the pharmacokinetic properties of fenfluramine. Healthy nonsmoking subjects aged 18 to 50years were enrolled in an open-label, crossover, Phase I pharmacokinetic and safety profile study and received 2 single 0.8-mg/kg doses of ZX008 (fenfluramine hydrochloride oral solution), 1 after a 10-hour overnight fast and the other 30 minutes after the start of consumption of a high-fat breakfast, in a randomly assigned order. A washout period of at least 9days separated the 2 treatment periods. Venous blood samples were taken before each dose and periodically for 72hours after each dose for determination of concentrations of fenfluramine and its active metabolite norfenfluramine. Plasma pharmacokinetic parameters were estimated for each subject by noncompartmental analysis. In the 13 subjects completing both treatment periods, food had no effect on the rate or extent of absorption and bioavailability of fenfluramine as assessed by fed vs fasted adjusted geometric mean observed plasma C max (59.1vs 56.7 ng/mL; NS) and AUC 0-∞ (1640vs 1600 ng · h/mL; NS). Additionally, there was no impact of food on systemic exposure of norfenfluramine. Seven subjects reported at least 1 treatment-emergent adverse event; all treatment-emergent adverse events were mild in severity. The bioequivalence and tolerability of single 0.8-mg/kg oral doses of ZX008 in the fed and fasted states support ZX008 administration without regard to meals. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Bioequivalence and pharmacokinetic evaluation of two formulations of risperidone 2 mg : an open-label, single-dose, fasting, randomized-sequence, two-way crossover study in healthy male Chinese volunteers.

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Liu, Yun; Zhang, Meng-qi; Jia, Jing-ying; Liu, Yan-mei; Liu, Gang-yi; Li, Shui-jun; Wang, Wei; Weng, Li-ping; Yu, Chen

2013-03-01

Risperidone is a benzisoxazole derivate and is effective in the treatment of schizophrenia and other psychiatric illnesses in adults and children. Although there are a few reports in the literature regarding the pharmacokinetic characteristics of risperidone, insufficient data on its pharmacokinetic properties in a Chinese population are available. To meet the requirements for marketing a new generic product, this study was designed to compare the pharmacokinetic properties and bioequivalence of two 2 mg tablet formulations of risperidone: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult male Chinese volunteers. A single-dose, open-label, randomized-sequence, 2 × 2 crossover study was conducted in fasted healthy male Chinese volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 1 tablet (2 mg each) of the test formulation (Risperidone tablet; Dr. Reddy's Laboratories Ltd., Hyderabad, India) or the reference formulation (Risperdal(®) tablet; Xian-Janssen Pharmaceutical Ltd., Xi-an, China), followed by a 2-week washout period and subsequent administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected over 96 hours. Plasma concentrations of the parent drug, risperidone, and its active metabolite, 9-hydroxy-risperidone, were analyzed by a liquid chromatography-tandem mass spectrometry method. The formulations would be considered bioequivalent if the 90% confidence intervals (CIs) of the natural log-transformed values were within the predetermined 80-125% equivalence range for the maximum plasma drug concentration (Cmax) and the area under the plasma concentration-time curve (AUC), in accordance with guidelines issued by the US Food and Drug Administration. Assessment of tolerability was based on recording of adverse events (AEs), monitoring of vital signs, electrocardiograms, and laboratory tests at baseline

An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch

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Zhang C

2017-03-01

Full Text Available Chao Zhang,1 Haiyan Li,2 Xin Xiong,1 Suodi Zhai,1 Yudong Wei,2 Shuang Zhang,2 Yuanyuan Zhang,1 Lin Xu,2 Li Liu1 1Department of Pharmacy, 2Institute of Clinical Trial, Peking University Third Hospital, Beijing, People’s Republic of China Abstract: We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE/gestodene (GSD transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet® were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax, extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations. Keywords: pharmacokinetics, safety, ethinylestradiol/gestodene, transdermal contraceptive patch

A single-dose, randomized, cross-over, two-way, open-label study for comparing the absorption of boswellic acids and its lecithin formulation.

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Riva, Antonella; Morazzoni, Paolo; Artaria, Christian; Allegrini, Pietro; Meins, Jürgen; Savio, Daniele; Appendino, Giovanni; Schubert-Zsilavecz, Manfred; Abdel-Tawab, Mona

2016-11-15

The oral administration of the gum resin extracts of Indian frankincense (Boswellia serrata Roxb. ex Colebr) results in very low plasma concentrations of boswellic acids (BAs), being far below the pharmacologically active concentrations required in vitro for anti-inflammatory activity. For that reason the use of Indian frankincense in clinical practice and pharmaceutical development has substantially lagged behind. Recently the application of new formulation technologies resulted in a formulation of frankincense extract with lecithin, which revealed improved absorption and tissue penetration of BAs in a rodent study, leading for the first time to plasma concentrations of BAs in the range of their anti-inflammatory activity. In order to verify these encouraging results in humans, the absorption of a standardized Boswellia serrata extract (BE) and its lecithin formulation (CSP) was comparatively investigated in healthy volunteers. According to a randomized cross-over design with two treatments, two sequences and two periods, 12 volunteers alternatively received the lecithin-formulated Boswellia extract (CSP) or the non-formulated Boswellia extract (BE) at a dosage of 2×250mg capsules. The plasma concentrations of the six major BAs (KBA, AKBA, βBA, αBA, AβBA, AαBA) were determined using LC/MS. With the exception of KBA, a significantly higher (both in terms of weight-to-weight and molar comparison) and quicker absorption of BAs from the lecithin formulation was observed, leading to C max in the range required for the interaction with their molecular targets. These findings pave the way to further studies evaluating the clinical potential of BAs, and verify the beneficial effect of lecithin formulation to improve the absorption of poorly soluble phytochemicals. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the Pharmacokinetic and Pharmacodynamic Interaction Between Nebivolol and Valsartan in Healthy Volunteers at Steady State.

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Chen, Chun Lin; Desai-Krieger, Daksha; Ortiz, Stephan; Kerolous, Majid; Wright, Harold M; Ghahramani, Parviz

2015-01-01

Combining different classes of antihypertensives is more effective for reducing blood pressure (BP) than increasing the dose of monotherapies. The aims of this phase I study were to investigate pharmacokinetic and pharmacodynamic interactions between nebivolol, a vasodilatory β1-selective blocker, and valsartan, an angiotensin II receptor blocker, and to assess safety and tolerability of the combination. This was a single-center, randomized, open-label, multiple-dose, 3-way crossover trial in 30 healthy adults aged 18-45 years. Participants were randomized into 1 of 6 treatment sequences (1:1:1:1:1:1) consisting of three 7-day treatment periods followed by a 7-day washout. Once-daily oral treatments comprised nebivolol (20 mg), valsartan (320 mg), and nebivolol-valsartan combination (20/320 mg). Outcomes included AUC0-τ,ss, Cmax,ss, Tmax,ss, changes in BP, pulse rate, plasma angiotensin II, plasma renin activity, 24-hour urinary aldosterone, and adverse events. Steady-state pharmacokinetic interactions were observed but deemed not clinically significant. Systolic and diastolic BP reduction was significantly greater with nebivolol-valsartan combination than with either monotherapy. The mean pulse rate associated with nebivolol and nebivolol-valsartan treatments was consistently lower than that associated with valsartan monotherapy. A sharp increase in mean day 7 plasma renin activity and plasma angiotensin II that occurred in valsartan-treated participants was significantly attenuated with concomitant nebivolol administration. Mean 24-hour urine aldosterone at day 7 was substantially decreased after combined treatment, as compared with either monotherapy. All treatments were safe and well tolerated. In conclusion, nebivolol and valsartan coadministration led to greater reductions in BP compared with either monotherapy; nebivolol and valsartan lower BP through complementary mechanisms.

Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomised, crossover study.

Science.gov (United States)

Bally, Lia; Thabit, Hood; Kojzar, Harald; Mader, Julia K; Qerimi-Hyseni, Jehona; Hartnell, Sara; Tauschmann, Martin; Allen, Janet M; Wilinska, Malgorzata E; Pieber, Thomas R; Evans, Mark L; Hovorka, Roman

2017-04-01

Tight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve glucose control while alleviating the risk of hypoglycaemia in adults with HbA 1c below 7·5% (58 mmol/mol). In this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA 1c below 7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2-4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2-4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard. The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9-10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02727231, and is completed. Between March 21 and June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10·5 percentage points higher (95% CI 7·6-13·4; pday-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA 1c below 7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies

Comparative fasting bioavailability of 2 bepotastine formulations in healthy male Chinese volunteers: an open-label, randomized, single-dose, 2-way crossover study.

Science.gov (United States)

Shentu, Jianzhong; Zhou, Huili; Hu, Xingjiang; Wu, Guolan; Wu, Lihua; Zhu, Meixiang; Zhai, You; Zheng, Yunliang; Liu, Jian

2014-04-01

Bepotastine is a second-generation histamine1 receptor antagonist that is used in the treatment of allergic rhinitis, urticaria, and pruritus associated with skin disease. A new generic formulation of bepotastine has been developed in China, and information concerning bioavailability and pharmacokinetic properties in the Chinese population has not been reported. The aim of the present study was to compare the bioavailability and pharmacokinetic properties of 2 tablet formulations of bepotastine, the 10-mg generic formulation (test) and a branded formulation (reference), in healthy male Chinese volunteers to obtain registration approval of the test formulation. A single-center, open-label, randomized, 2-way crossover study with a 1-week washout period was conducted in 24 healthy male volunteers. Blood samples were collected for 16 hours after a single dose of the 10-mg bepotastine test formulation or the reference formulation. Plasma bepotastine concentrations were determined using a validated LC-MS/MS method. Cmax, Tmax, AUC₀-t, AUC₀-∞, and t½ were determined using noncompartmental analysis. The formulations were considered bioequivalent if the 90% CIs for the log-transformed Cmax and AUC values were within the predetermined interval of 75% to 133% and 80% to 125%, respectively, according to the guidelines of the China Food and Drug Administration. No significant differences were found in mean (SD) pharmacokinetic parameters between the test and reference drugs, including Cmax (74.81 [9.91] ng/mL vs 78.60 [29.58] ng/mL), AUC₀-t (295.55[115.29] ng·h/mL vs 299.17[109.29] ng·h/mL), and AUC0-∞ (305.28 [118.50] ng·h/mL vs 310.90 [112.20] ng·h/mL). The mean (SD) t½ values of the test and reference formulations were 2.53 (0.50) hours and 2.62 (0.41) hours, respectively. The 90% CIs of the treatment ratios for the logarithmic transformed values of Cmax, AUC₀-t, and AUC₀-∞ were 86.96% to 101.80%, 93.22% to 104.13%, and 92.66% to 103.30%, respectively

Moderate alcohol consumption increases insulin sensitivity and ADIPOQ expression in postmenopausal women: A randomised, crossover trial

NARCIS (Netherlands)

Joosten, M.M.; Beulens, J.W.J.; Kersten, S.; Hendriks, H.F.J.

2008-01-01

Aims/hypothesis: To determine whether 6 weeks of daily, moderate alcohol consumption increases expression of the gene encoding adiponectin (ADIPOQ) and plasma levels of the protein, and improves insulin sensitivity in postmenopausal women. Methods: In a randomised, open-label, crossover trial

Randomized, open-label, 5-way crossover study to evaluate the pharmacokinetic/pharmacodynamic interaction between furosemide and the non-steroidal anti-inflammatory drugs diclofenac and ibuprofen in healthy volunteers.

Science.gov (United States)

Paterson, C A; Jacobs, D; Rasmussen, S; Youngberg, S P; McGuinness, N

2011-08-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce renal complications in patients taking loop diuretics. This study investigated the pharmacokinetic/pharmacodynamic effects and safety profile of orally administered diclofenac sodium, ibuprofen and diclofenac epolamine topical patch (DETP) on furosemide in healthy adult subjects. This open-label, randomized, 5-way crossover study was conducted in 40 subjects (aged 19 - 45 y). Diclofenac (75 mg taken orally twice daily), DETP (1.3% applied topically twice daily), or ibuprofen (800 mg taken orally thrice daily) was administered for 3 consecutive days, followed by co-administration with furosemide (given intravenously as 20 mg/2 min). Plasma furosemide and NSAID concentrations, urine furosemide, sodium and potassium concentrations and urine output were determined throughout the 24 h period following furosemide administration. Orally administered ibuprofen significantly increased furosemide AUC(0-t) (37%) and AUC(0-inf) (36%) and decreased total body CL (27%), R(max) (19%) and CLR (23%) geometric mean ratios compared with furosemide control. Oral and topical diclofenac had no pharmacokinetic effects on furosemide. Ibuprofen increased sodium excretion (Ae(0-24), 16%) and decreased sodium R(max) (15%), and oral diclofenac decreased urine output (Vu(0-24), 15%). DETP had no effect on furosemide pharmacodynamics; total systemic exposure to diclofenac during DETP treatment was diclofenac. Treatments were generally safe, with 25 subjects reporting a total of 112 adverse events. Pharmacodynamic effects were seen with oral diclofenac (urine output) and ibuprofen (urine sodium excretion). Furosemide also affected plasma and urine pharmacokinetic profiles. Pharmacologic effects of DETP on furosemide were not observed under these conditions. Additional research is warranted to delineate the potential interactions of other NSAIDs with furosemide and other loop diuretics.

Laserlight cues for gait freezing in Parkinson's disease: an open-label study.

Science.gov (United States)

Donovan, S; Lim, C; Diaz, N; Browner, N; Rose, P; Sudarsky, L R; Tarsy, D; Fahn, S; Simon, D K

2011-05-01

Freezing of gait (FOG) and falls are major sources of disability for Parkinson's disease (PD) patients, and show limited responsiveness to medications. We assessed the efficacy of visual cues for overcoming FOG in an open-label study of 26 patients with PD. The change in the frequency of falls was a secondary outcome measure. Subjects underwent a 1-2 month baseline period of use of a cane or walker without visual cues, followed by 1 month using the same device with the laserlight visual cue. The laserlight visual cue was associated with a modest but significant mean reduction in FOG Questionnaire (FOGQ) scores of 1.25 ± 0.48 (p = 0.0152, two-tailed paired t-test), representing a 6.6% improvement compared to the mean baseline FOGQ scores of 18.8. The mean reduction in fall frequency was 39.5 ± 9.3% with the laserlight visual cue among subjects experiencing at least one fall during the baseline and subsequent study periods (p = 0.002; two-tailed one-sample t-test with hypothesized mean of 0). Though some individual subjects may have benefited, the overall mean performance on the timed gait test (TGT) across all subjects did not significantly change. However, among the 4 subjects who underwent repeated testing of the TGT, one showed a 50% mean improvement in TGT performance with the laserlight visual cue (p = 0.005; two-tailed paired t-test). This open-label study provides evidence for modest efficacy of a laserlight visual cue in overcoming FOG and reducing falls in PD patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Treadmill training with partial body weight support compared with conventional gait training for low-functioning children and adolescents with nonspastic cerebral palsy: a two-period crossover study.

Science.gov (United States)

Su, Ivan Y W; Chung, Kenny K Y; Chow, Daniel H K

2013-12-01

Partial body weight-supported treadmill training has been shown to be effective in gait training for patients with neurological disorders such as spinal cord injuries and stroke. Recent applications on children with cerebral palsy were reported, mostly on spastic cerebral palsy with single subject design. There is lack of evidence on the effectiveness of such training for nonspastic cerebral palsy, particularly those who are low functioning with limited intellectual capacity. This study evaluated the effectiveness of partial body weight-supported treadmill training for improving gross motor skills among these clients. A two-period randomized crossover design with repeated measures. A crossover design following an A-B versus a B-A pattern was adopted. The two training periods consisted of 12-week partial body weight-supported treadmill training (Training A) and 12-week conventional gait training (Training B) with a 10-week washout in between. Ten school-age participants with nonspastic cerebral palsy and severe mental retardation were recruited. The Gross Motor Function Measure-66 was administered immediately before and after each training period. Significant improvements in dimensions D and E of the Gross Motor Function Measure-66 and the Gross Motor Ability Estimator were obtained. Our findings revealed that the partial body weight-supported treadmill training was effective in improving gross motor skills for low-functioning children and adolescents with nonspastic cerebral palsy. .

Effect of Steady-State Faldaprevir on Pharmacokinetics of Atorvastatin or Rosuvastatin in Healthy Volunteers: A Prospective Open-Label, Fixed-Sequence Crossover Study.

Science.gov (United States)

Huang, Fenglei; Marzin, Kristell; Koenen, Rüdiger; Kammerer, Klaus Peter; Strelkowa, Natalja; Elgadi, Mabrouk; Quinson, Anne-Marie; Haertter, Sebastian

2017-10-01

Faldaprevir (FDV) is a potent, orally administered inhibitor of hepatitis C virus protease. It inhibits multiple cytochrome P-450 enzymes and multiple membrane transporters. The objective of this study was to evaluate the effect of steady-state faldaprevir on the pharmacokinetics (PK) of a single dose of atorvastatin or rosuvastatin. In this single-center, open-label, fixed-sequence crossover study, 33 healthy adult male and female volunteers were given either atorvastatin 10 mg (n = 16) or rosuvastatin 10 mg (n = 17) on day 1. Subjects subsequently received 240 mg twice daily of faldaprevir (loading dose) on day 5, followed by 240 mg faldaprevir once daily from day 6 to day 10, with an additional single dose of atorvastatin (10 mg) or rosuvastatin (10 mg) given on day 10. PK samples for the statins were collected on days 1-3 and days 10-12. Concomitant administration with faldaprevir led to approximately 9-fold and 34-fold increases in AUC 0-∞ and C max , respectively, of atorvastatin and approximately 15-fold and 33-fold increases in AUC 0-∞ and C max , respectively, of rosuvastatin, compared with the statins given alone. Exposure to the major metabolites (ortho-hydroxyatorvastatin and N-desmethylrosuvastatin) was increased to a similar magnitude as that of the parent compounds. The marked drug-drug interaction observed is most likely related to the inhibitory effects of faldaprevir on transporters, particularly hepatic uptake transporters such as OTAP1B1 and OATP1B3. Given the significant increase in exposure to statins in healthy volunteers, coadministration of faldaprevir with statins should be avoided. © 2017, The American College of Clinical Pharmacology.

Pressure and Temperature Sensors Using Two Spin Crossover Materials

Science.gov (United States)

Jureschi, Catalin-Maricel; Linares, Jorge; Boulmaali, Ayoub; Dahoo, Pierre Richard; Rotaru, Aurelian; Garcia, Yann

2016-01-01

The possibility of a new design concept for dual spin crossover based sensors for concomitant detection of both temperature and pressure is presented. It is conjectured from numerical results obtained by mean field approximation applied to a Ising-like model that using two different spin crossover compounds containing switching molecules with weak elastic interactions it is possible to simultaneously measure P and T. When the interaction parameters are optimized, the spin transition is gradual and for each spin crossover compounds, both temperature and pressure values being identified from their optical densities. This concept offers great perspectives for smart sensing devices. PMID:26848663

Pressure and Temperature Sensors Using Two Spin Crossover Materials.

Science.gov (United States)

Jureschi, Catalin-Maricel; Linares, Jorge; Boulmaali, Ayoub; Dahoo, Pierre Richard; Rotaru, Aurelian; Garcia, Yann

2016-02-02

The possibility of a new design concept for dual spin crossover based sensors for concomitant detection of both temperature and pressure is presented. It is conjectured from numerical results obtained by mean field approximation applied to a Ising-like model that using two different spin crossover compounds containing switching molecules with weak elastic interactions it is possible to simultaneously measure P and T. When the interaction parameters are optimized, the spin transition is gradual and for each spin crossover compounds, both temperature and pressure values being identified from their optical densities. This concept offers great perspectives for smart sensing devices.

Pressure and Temperature Sensors Using Two Spin Crossover Materials

Directory of Open Access Journals (Sweden)

Catalin-Maricel Jureschi

2016-02-01

Full Text Available The possibility of a new design concept for dual spin crossover based sensors for concomitant detection of both temperature and pressure is presented. It is conjectured from numerical results obtained by mean field approximation applied to a Ising-like model that using two different spin crossover compounds containing switching molecules with weak elastic interactions it is possible to simultaneously measure P and T. When the interaction parameters are optimized, the spin transition is gradual and for each spin crossover compounds, both temperature and pressure values being identified from their optical densities. This concept offers great perspectives for smart sensing devices.

A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women.

Science.gov (United States)

Shifren, Jan L; Desindes, Sophie; McIlwain, Marilyn; Doros, Gheorghe; Mazer, Norman A

2007-01-01

To compare the changes induced by oral versus transdermal estrogen therapy on the total and free serum concentrations of testosterone (T), thyroxine (T4), and cortisol (C) and the concentrations of their serum binding globulins sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin in naturally menopausal women. Randomized, open-label, crossover. Interventions included a 6-week withdrawal from previous hormone therapy (baseline), followed in randomized order by 12 weeks of oral conjugated equine estrogens (CEE) (0.625 mg/d) and 12 weeks of transdermal estradiol (TD E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both transdermal estrogen therapy regimens. Twenty-seven women were enrolled in the study, and 25 completed both treatment periods. The mean(SD) percentage changes from baseline of sex hormone-binding globulin, total T, and free T with oral CEE were +132.1% (74.5%), +16.4% (43.8%), and -32.7% (25.9%), respectively, versus +12.0% (25.1%), +1.2% (43.7%), and +1.0% (45.0%) with TD E2. The mean (SD) percentage changes of thyroxine-binding globulin, total T4, and free T4 with oral CEE were +39.9% (20.1%), +28.4% (29.2%), and -10.4% (22.3%), respectively, versus +0.4% (11.1%), -0.7% (16.5%), and +0.2% (26.6%) with TD E2. The mean (SD) percentage changes of cortisol-binding globulin, total C, and free C with oral CEE were +18.0% (19.5%), +29.2% (46.3%), and +50.4% (126.5%), respectively, versus -2.2% (11.3%), -6.7% (30.8%), and +1.8% (77.1%) with TD E2. Concentrations of all hormones and binding globulins were significantly different (P < or = 0.003) during administration of oral versus transdermal estrogen therapy, except for free T4 and free C. Compared with oral CEE, TD E2 exerts minimal effects on the total and free concentrations of T, T4, and C and their binding proteins.

A Randomized, Two-Way Crossover Study to Evaluate the Pharmacokinetics of Caffeine Delivered Using Caffeinated Chewing Gum Versus a Marketed Caffeinated Beverage in Healthy Adult Volunteers.

Science.gov (United States)

Sadek, Paul; Pan, Xiao; Shepherd, Phil; Malandain, Elise; Carney, John; Coleman, Hugh

2017-12-01

Background: This study was conducted to compare the pharmacokinetics of caffeine delivered using caffeinated chewing gum to that delivered using a marketed caffeinated beverage (instant coffee) in 16 healthy adult volunteers. Materials and Methods: This was a controlled open-label, randomized, two-period crossover study. Caffeinated chewing gum and a serving of instant coffee, each containing ∼50 mg caffeine, were administered with blood samples collected before and up to 24 hours after administration starts. Plasma caffeine levels were analyzed using validated liquid chromatography coupled with tandem mass spectrometry methodology. Results: There were no statistical differences between the two caffeine products in t max ( p  = 0.3308) and k a ( p  = 0.3894). Although formulated at ∼50 mg caffeine each, mean dose released from chewing gum was ∼18% less than beverage. Dose-normalized area under the concentration-time curve (AUC) 0-t , AUC 0-∞ , and C max was similar between products. Although the criteria were not set a priori and the study was not powered for concluding bioequivalence, the 90% confidence intervals fell within the bioequivalence limit of 80% to 125%. Conclusions: Existing scientific literature on caffeine, based mostly on data from caffeinated beverages, can be leveraged to support the safety of caffeine delivered by chewing gum and current maximum safe caffeine dose advice should be applicable irrespective of delivery method.

Targeted HIV Screening in Eight Emergency Departments: The DICI-VIH Cluster-Randomized Two-Period Crossover Trial.

Science.gov (United States)

Leblanc, Judith; Hejblum, Gilles; Costagliola, Dominique; Durand-Zaleski, Isabelle; Lert, France; de Truchis, Pierre; Verbeke, Geert; Rousseau, Alexandra; Piquet, Hélène; Simon, François; Pateron, Dominique; Simon, Tabassome; Crémieux, Anne-Claude

2017-10-30

This study compares the effectiveness and cost-effectiveness of nurse-driven targeted HIV screening alongside physician-directed diagnostic testing (intervention strategy) with diagnostic testing alone (control strategy) in 8 emergency departments. In this cluster-randomized, 2-period, crossover trial, 18- to 64-year-old patients presenting for reasons other than potential exposure to HIV were included. The strategy applied first was randomly assigned. During both periods, diagnostic testing was prescribed by physicians following usual care. During the intervention periods, patients were asked to complete a self-administered questionnaire. According to their answers, the triage nurse suggested performing a rapid test to patients belonging to a high-risk group. The primary outcome was the proportion of new diagnoses among included patients, which further refers to effectiveness. A secondary outcome was the intervention's incremental cost (health care system perspective) per additional diagnosis. During the intervention periods, 74,161 patients were included, 16,468 completed the questionnaire, 4,341 belonged to high-risk groups, and 2,818 were tested by nurses, yielding 13 new diagnoses. Combined with 9 diagnoses confirmed through 97 diagnostic tests, 22 new diagnoses were established. During the control periods, 74,166 patients were included, 92 were tested, and 6 received a new diagnosis. The proportion of new diagnoses among included patients was higher during the intervention than in the control periods (3.0 per 10,000 versus 0.8 per 10,000; difference 2.2 per 10,000, 95% CI 1.3 to 3.6; relative risk 3.7, 95% CI 1.4 to 9.8). The incremental cost was €1,324 per additional new diagnosis. The combined strategy of targeted screening and diagnostic testing was effective. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Ethosuximide for Essential Tremor: An Open-Label Trial

OpenAIRE

Gironell, Alexandre; Marin-Lahoz, Juan

2016-01-01

Background: T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high inci...

Efficacy of the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program among patients with mild cognitive impairment: a randomized controlled crossover trial.

Science.gov (United States)

Han, Ji Won; Son, Kyung Lak; Byun, Hye Jin; Ko, Ji Won; Kim, Kayoung; Hong, Jong Woo; Kim, Tae Hyun; Kim, Ki Woong

2017-06-06

Spaced retrieval training (SRT) is a nonpharmacological intervention for mild cognitive impairment (MCI) and dementia that trains the learning and retention of target information by recalling it over increasingly long intervals. We recently developed the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program as a convenient, self-administered tablet-based SRT program. We also demonstrated the utility of USMART for improving memory in individuals with MCI through an open-label uncontrolled trial. This study had an open-label, single-blind, randomized, controlled, two-period crossover design. Fifty patients with MCI were randomized into USMART-usual care and usual care-USMART treatment sequences. USMART was completed or usual care was provided biweekly over a 4-week treatment period with a 2-week washout period between treatment periods. Primary outcome measures included the Word List Memory Test, Word List Recall Test (WLRT), and Word List Recognition Test. Outcomes were measured at baseline, week 5, and week 11 by raters who were blinded to intervention type. An intention-to-treat analysis and linear mixed modeling were used. Of 50 randomized participants, 41 completed the study (18% dropout rate). The USMART group had larger improvements in WLRT score (effect size = 0.49, p = 0.031) than the usual care group. There were no significant differences in other primary or secondary measures between the USMART and usual care groups. Moreover, no USMART-related adverse events were reported. The 4-week USMART modestly improved information retrieval in older people with MCI, and was well accepted with minimal technical support. ClinicalTrials.gov NCT01688128 . Registered 12 September 2012.

Notes on testing equality and interval estimation in Poisson frequency data under a three-treatment three-period crossover trial.

Science.gov (United States)

Lui, Kung-Jong; Chang, Kuang-Chao

2016-10-01

When the frequency of event occurrences follows a Poisson distribution, we develop procedures for testing equality of treatments and interval estimators for the ratio of mean frequencies between treatments under a three-treatment three-period crossover design. Using Monte Carlo simulations, we evaluate the performance of these test procedures and interval estimators in various situations. We note that all test procedures developed here can perform well with respect to Type I error even when the number of patients per group is moderate. We further note that the two weighted-least-squares (WLS) test procedures derived here are generally preferable to the other two commonly used test procedures in the contingency table analysis. We also demonstrate that both interval estimators based on the WLS method and interval estimators based on Mantel-Haenszel (MH) approach can perform well, and are essentially of equal precision with respect to the average length. We use a double-blind randomized three-treatment three-period crossover trial comparing salbutamol and salmeterol with a placebo with respect to the number of exacerbations of asthma to illustrate the use of these test procedures and estimators. © The Author(s) 2014.

Atomoxetine Open-Label Trial in ADHD

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2002-07-01

Full Text Available Atomoxetine (originally named tomoxetine, a new therapy for attention deficit hyperactivity disorder (ADHD marketed by Eli Lilly, was compared to methylphenidate in a prospective, randomized, open-label study for 10 weeks duration, at the University of Nebraska Medical Center, Massachusetts General Hospital, Mount Sinai Medical Center, Carolinas Medical Center, and Lilly Research Laboratories.

Crossover of two power laws in the anomalous diffusion of a two lipid membrane.

Science.gov (United States)

Bakalis, Evangelos; Höfinger, Siegfried; Venturini, Alessandro; Zerbetto, Francesco

2015-06-07

Molecular dynamics simulations of a bi-layer membrane made by the same number of 1-palmitoyl-2-oleoyl-glycero-3-phospho-ethanolamine and palmitoyl-oleoyl phosphatidylserine lipids reveal sub-diffusional motion, which presents a crossover between two different power laws. Fractional Brownian motion is the stochastic mechanism that governs the motion in both regimes. The location of the crossover point is justified with simple geometrical arguments and is due to the activation of the mechanism of circumrotation of lipids about each other.

Crossover of two power laws in the anomalous diffusion of a two lipid membrane

Energy Technology Data Exchange (ETDEWEB)

Bakalis, Evangelos, E-mail: ebakalis@gmail.com, E-mail: francesco.zerbetto@unibo.it; Höfinger, Siegfried; Zerbetto, Francesco, E-mail: ebakalis@gmail.com, E-mail: francesco.zerbetto@unibo.it [Dipartimento di Chimica “G. Ciamician”, Universita’ di Bologna, Via F. Selmi 2, 40126 Bologna (Italy); Venturini, Alessandro [Institute for the Organic Synthesis and Photoreactivity, National Research Council of Italy, Via Gobetti 101, 40129 Bologna (Italy)

2015-06-07

Molecular dynamics simulations of a bi-layer membrane made by the same number of 1-palmitoyl-2-oleoyl-glycero-3-phospho-ethanolamine and palmitoyl-oleoyl phosphatidylserine lipids reveal sub-diffusional motion, which presents a crossover between two different power laws. Fractional Brownian motion is the stochastic mechanism that governs the motion in both regimes. The location of the crossover point is justified with simple geometrical arguments and is due to the activation of the mechanism of circumrotation of lipids about each other.

Testing equality and interval estimation in binary responses when high dose cannot be used first under a three-period crossover design.

Science.gov (United States)

Lui, Kung-Jong; Chang, Kuang-Chao

2015-01-01

When comparing two doses of a new drug with a placebo, we may consider using a crossover design subject to the condition that the high dose cannot be administered before the low dose. Under a random-effects logistic regression model, we focus our attention on dichotomous responses when the high dose cannot be used first under a three-period crossover trial. We derive asymptotic test procedures for testing equality between treatments. We further derive interval estimators to assess the magnitude of the relative treatment effects. We employ Monte Carlo simulation to evaluate the performance of these test procedures and interval estimators in a variety of situations. We use the data taken as a part of trial comparing two different doses of an analgesic with a placebo for the relief of primary dysmenorrhea to illustrate the use of the proposed test procedures and estimators.

Pharmacokinetic comparison of sustained- and immediate-release oral formulations of cilostazol in healthy Korean subjects: a randomized, open-label, 3-part, sequential, 2-period, crossover, single-dose, food-effect, and multiple-dose study.

Science.gov (United States)

Lee, Donghwan; Lim, Lay Ahyoung; Jang, Seong Bok; Lee, Yoon Jung; Chung, Jae Yong; Choi, Jong Rak; Kim, Kiyoon; Park, Jin Woo; Yoon, Hosang; Lee, Jaeyong; Park, Min Soo; Park, Kyungsoo

2011-12-01

A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower C(max) and a similar AUC to the immediate-release (IR) formulation. The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, 3-part, sequential, open-label, 2-period crossover study. Each part consisted of different subjects between the ages of 19 and 55 years. In part 1, each subject received a single dose of SR (200 mg × 1 tablet, once daily) and IR (100 mg × 2 tablets, BID) formulations of cilostazol orally 7 days apart in a fasted state. In part 2, each subject received a single dose of the SR (200 mg × 1 tablet, once daily) formulation of cilostazol 7 days apart in a fasted and a fed state. In part 3, each subject received multiple doses of the 2 formulations for 8 consecutive days 21 days apart. Blood samples were taken for 72 hours after the dose. Cilostazol pharmacokinetics were determined for both the parent drug and its metabolites (OPC-13015 and OPC-13213). Adverse events were evaluated through interviews and physical examinations. Among the 92 enrolled subjects (66 men, 26 women; part 1, n = 26; part 2, n = 26; part 3, n = 40), 87 completed the study. In part 1, all the primary pharmacokinetic parameters satisfied the criterion for assumed bioequivalence both in cilostazol and its metabolites, yielding 90% CI ratios of 0.9624 to 1.2323, 0.8873 to 1.1208, and 0.8919 to 1.1283 for C(max) and 0.8370 to 1.0134, 0.8204 to 0.9807, and 0.8134 to 0.9699 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213, respectively. In part 2, food intake increased C(max) and AUC significantly (P food and 23 with a high

Open-label extension studies: do they provide meaningful information on the safety of new drugs?

Science.gov (United States)

Day, Richard O; Williams, Kenneth M

2007-01-01

The number of open-label extension studies being performed has increased enormously in recent years. Often it is difficult to differentiate between these extension studies and the double-blind, controlled studies that preceded them. If undertaken primarily to gather more patient-years of exposure to the new drug in order to understand and gain confidence in its safety profile, open-label extension studies can play a useful and legitimate role in drug development and therapeutics. However, this can only occur if the open-label extension study is designed, executed, analysed and reported competently. Most of the value accrued in open-label extension studies is gained from a refinement in the perception of the expected incidence of adverse effects that have most likely already been identified as part of the preclinical and clinical trial programme. We still have to rely heavily on post-marketing safety surveillance systems to alert us to type B (unpredictable) adverse reactions because open-label extension studies are unlikely to provide useful information about these types of often serious and relatively rare adverse reactions. Random allocation into test and control groups is needed to produce precise incidence data on pharmacologically expected, or type A, adverse effects. Some increased confidence about incidence rates might result from the open-label extension study; however, as these studies are essentially uncontrolled and biased, the data are not of great value. Other benefits have been proposed to be gained from open-label extension studies. These include ongoing access to an effective but otherwise unobtainable medicine by the volunteers who participated in the phase III pivotal trials. However, there are unappreciated ethical issues about the appropriateness of enrolling patients whose response to previous treatment is uncertain, largely because treatment allocation in the preceding randomised, double-blind, controlled trial has not been revealed at the

Bioequivalence of generic alendronate sodium tablets (70 mg to Fosamax® tablets (70 mg in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

Directory of Open Access Journals (Sweden)

Zhang Y

2017-07-01

Full Text Available Yifan Zhang,1 Xiaoyan Chen,1 Yunbiao Tang,2 Youming Lu,1 Lixia Guo,1 Dafang Zhong1 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 2Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People’s Republic of China Purpose: The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet. Materials and methods: A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg. Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA and European Medicines Agency (EMA reference-scaled average bioequivalence (RSABE methods. Results: The average maximum concentrations (Cmax of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h·ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were -0.16 and -0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129

Chiral crossover transition in a finite volume

Science.gov (United States)

Shi, Chao; Jia, Wenbao; Sun, An; Zhang, Liping; Zong, Hongshi

2018-02-01

Finite volume effects on the chiral crossover transition of strong interactions at finite temperature are studied by solving the quark gap equation within a cubic volume of finite size L. With the anti-periodic boundary condition, our calculation shows the chiral quark condensate, which characterizes the strength of dynamical chiral symmetry breaking, decreases as L decreases below 2.5 fm. We further study the finite volume effects on the pseudo-transition temperature {T}{{c}} of the crossover, showing a significant decrease in {T}{{c}} as L decreases below 3 fm. Supported by National Natural Science Foundation of China (11475085, 11535005, 11690030, 51405027), the Fundamental Research Funds for the Central Universities (020414380074), China Postdoctoral Science Foundation (2016M591808) and Open Research Foundation of State Key Lab. of Digital Manufacturing Equipment & Technology in Huazhong University of Science & Technology (DMETKF2015015)

Electric crossover

International Nuclear Information System (INIS)

Schuster, R.M.; Luria, N.G.

1977-01-01

This invention concerns an electric crossover that makes a steam and pressure-tight seal for a conductor crossing two separate walls of a nuclear reactor vessel that seismic tremors or thermal expansion of the walls and conductor subject to relative displacements. The conductors, that have to cross the vessels, are fixed to the walls of the vessel in crossover systems fitted in crossover channels made in the walls of the vessel on their initial manufacture. The separate walls of the vessel move independently when they undergo an earth tremor or a temperature change between the walls or between the conductor. This shift can damage the conductor or the crossover system and this could give rise to cause steam or other materials to leak in the reactor should leaks occur in the primary system. Furthermore, in the case of medium or high power conductors, which are relatively rigid, the non-alignment of the crossover channels can bring about awkward stresses in the conductors or their protective sheathing. The aims of this invention are fulfilled by designing an electric crossover to pass at least one conductor through the two separate walls of a vessels, that includes an initial sub-assembly crossover, secured in a leak-tight manner to the first wall and a second sub-sessembly crossover in sliding or rolling contact with the second wall, whilst forming a leak-tight seal with it [fr

C2 Nerve Field Stimulation for the Treatment of Fibromyalgia: A Prospective, Double-blind, Randomized, Controlled Cross-over Study.

Science.gov (United States)

Plazier, Mark; Ost, Jan; Stassijns, Gaëtane; De Ridder, Dirk; Vanneste, Sven

2015-01-01

Fibromyalgia is a condition characterized by widespread chronic pain. Due to the high prevalence and high costs, it has a substantial burden on society. Treatment results are diverse and only help a small subset of patients. C2 nerve field stimulation, aka occipital nerve stimulation, is helpful and a minimally invasive treatment for primary headache syndromes. Small C2 pilot studies seem to be beneficial in fibromyalgia. Forty patients were implanted with a subcutaneous electrode in the C2 dermatoma as part of a prospective, double-blind, randomized, controlled cross-over study followed by an open label follow up period of 6 months. The patients underwent 2 week periods of different doses of stimulation consisting of minimal (.1 mA), subthreshold, and suprathreshold (for paresthesias) in a randomized order. Twenty seven patients received a permanent implant and 25 completed the 6 month open label follow up period. During the 6 week trial phase of the study, patients had an overall decrease of 36% on the fibromyalgia impact questionnaire (FIQ), a decrease of 33% fibromyalgia pain and improvement of 42% on the impact on daily life activities and quality. These results imply an overall improvement in the disease burden, maintained at 6 months follow up, as well as an improvement in life quality of 50%. Seventy six percent of patients were satisfied or very satisfied with their treatment. There seems to be a dose-response curve, with increasing amplitudes leading to better clinical outcomes. Subcutaneous C2 nerve field stimulation seems to offer a safe and effective treatment option for selected medically intractable patients with fibromyalgia. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-term safety and efficacy of etanercept in patients with psoriasis: an open-label study.

NARCIS (Netherlands)

Leonardi, C.; Strober, B.; Gottlieb, A.B.; Elewski, B.E.; Ortonne, J.P.; Kerkhof, P.C.M. van de; Chiou, C.F.; Dunn, M.; Jahreis, A.

2010-01-01

BACKGROUND: In two previous phase 3 studies, up to 60 weeks of etanercept therapy significantly improved the symptoms of psoriasis and was well tolerated. OBJECTIVE: To evaluate the long-term safety of etanercept in an open-label extension study for up to 72 weeks in patients with moderate-to-severe

Postural and Balance Disorders in Patients with Parkinson's Disease: A Prospective Open-Label Feasibility Study with Two Months of Action Observation Treatment

Science.gov (United States)

Santamato, Andrea; Ranieri, Maurizio; Cinone, Nicoletta; Stuppiello, Lucia Anna; Valeno, Giovanni; De Sanctis, Jula Laura; Fortunato, Francesca; Solfrizzi, Vincenzo; Greco, Antonio; Seripa, Davide; Panza, Francesco

2015-01-01

Action observation treatment has been proposed as therapeutic option in rehabilitation of patients affected by Parkinson's disease (PD) to improve freezing of gait episodes. The purpose of this prospective open-label feasibility study was to evaluate the impact of 8-week action observation training (video-therapy) for the treatment of postural instability and balance impairment in PD patients. Fifteen PD patients aged under 80 years with scores of 1 to 3 on the Hoehn and Yahr staging and without evidence of freezing of gait were recruited. They underwent 24 sessions of video-therapy training based on carefully watching video clips on motor tasks linked to balance, subsequently performing the same observed movements. No statistically significant differences were observed in the identified outcome measures with the Berg Balance Scale and the Activities-Specific Balance Confidence Scale after two months of follow-up. In the present study, a short course of action observation treatment seems to be not effective in reducing balance impairments and postural instability in patients affected by mild to moderate PD. Further studies with larger samples, longer follow-up period, and standardized protocols of action observation treatment are needed to investigate the effects of this rehabilitation technique in the management of postural and balance disorders of PD patients. PMID:26798551

Spin-Dependent Scattering Effects and Dimensional Crossover in a Quasi-Two-Dimensional Disordered Electron System

Institute of Scientific and Technical Information of China (English)

YANG YongHong; WANG YongGang; LIU Mei; WANG Jin

2002-01-01

Two kinds of spin-depcndcnt scattering effects (magnetic-iinpurity and spin-orbit scatterings) axe investi-gated theoretically in a quasi-two-dimensional (quasi-2D) disordered electron system. By making use of the diagrammatictechniques in perturbation theory, we have calculated the dc conductivity and magnetoresistance due to weak-localizationeffects, the analytical expressions of them are obtained as functions of the interlayer hopping energy and the charac-teristic times: elastic, inelastic, magnetic and spin-orbit scattering times. The relevant dimensional crossover behaviorfrom 3D to 2D with decreasing the interlayer coupling is discussed, and the condition for the crossover is shown to bedependent on the aforementioned scattering times. At low temperature there exists a spin-dcpendent-scattering-induccddimensional crossover in this system.

One-particle versus two-particle crossover in weakly coupled Hubbard chains and ladders: perturbative renormalization group approach

International Nuclear Information System (INIS)

Kishine, Jun-Ichiro; Yonemitsu, Kenji

1998-01-01

Physical nature of dimensional crossovers in weakly coupled Hubbard chains and ladders has been discussed within the framework of the perturbative renormalization-group (PRG) approach. The difference between these two cases originates from different universality classes which the corresponding isolated systems belong to. In the present work, we discuss the nature of the dimensional crossovers in the weakly coupled chains and ladders, with emphasis on the difference between the two cases within the framework of the PRG approach. The difference of the universality class of the isolated chain and ladder profoundly affects the relevance or irrelevance of the inter-chain/ladder one-particle hopping. The strong coupling phase of the isolated ladder makes the one-particle process irrelevant so that the d-wave superconducting transition can be induced via the two-particle crossover in the weakly coupled ladders. The weak coupling phase of the isolated chain makes the one-particle process relevant so that the two-particle crossover can hardly be realized in the coupled chains. (Copyright (1998) World Scientific Publishing Co. Pte. Ltd)

Randomized, open-label, single-dose, crossover, relative bioavailability study in healthy adults, comparing the pharmacokinetics of rabeprazole granules administered using soft food or infant formula as dosing vehicle versus suspension.

Science.gov (United States)

Thyssen, An; Solanki, Bhavna; Treem, William

2012-07-01

A sprinkle capsule formulation containing enteric-coated, delayed-release rabeprazole granules is being developed for the treatment of children with gastrointestinal reflux disease. The granules are designed to be mixed with vehicles that facilitate delivery to children, who may be unable to swallow solid formulations. The primary objective of this study-conducted on the sponsor's initiative-was to compare the bioavailability of rabeprazole granules when mixed with various dosing vehicles (small amount of soft food or infant formula) with that of a rabeprazole suspension with inactive vehicle granules (reference), to determine which dosing vehicle can be used to deliver rabeprazole in children. Tolerability was also assessed. This single-center, single-dose, randomized, open-label, 5-period crossover study was conducted in 35 healthy adult subjects. In a randomized sequence, fasting subjects received a single dose of 10-mg rabeprazole granules per treatment period, mixed with small amounts of 1 of 5 dosing vehicles (a strawberry-flavored suspension of rabeprazole granules with inactive vehicle granules reconstituted with water, yogurt [1 tablespoon], applesauce [1 tablespoon], or infant formula [5 mL], or a suspension of rabeprazole granules with inactive vehicle tablet reconstituted with water). Full plasma pharmacokinetic (PK) profiles of rabeprazole and its thioether metabolite were collected; concentrations were estimated via LC-MS/MS. PK properties were estimated using noncompartmental methods; 90% CIs around least squares mean test-to-reference ratios were calculated for C(max) and AUC values. All treatment-emergent adverse events (TEAEs) were recorded and assessed for severity (mild, moderate, or severe) and relationship to study drug. A total of 35 subjects were enrolled (mean age, 38 years; 54.3% female; 100% white; mean weight, 71.4 kg). Thirty-four subjects completed the study. Rabeprazole and rabeprazole thioether plasma PK properties were comparable

Postural and Balance Disorders in Patients with Parkinson’s Disease: A Prospective Open-Label Feasibility Study with Two Months of Action Observation Treatment

Directory of Open Access Journals (Sweden)

Andrea Santamato

2015-01-01

Full Text Available Action observation treatment has been proposed as therapeutic option in rehabilitation of patients affected by Parkinson’s disease (PD to improve freezing of gait episodes. The purpose of this prospective open-label feasibility study was to evaluate the impact of 8-week action observation training (video-therapy for the treatment of postural instability and balance impairment in PD patients. Fifteen PD patients aged under 80 years with scores of 1 to 3 on the Hoehn and Yahr staging and without evidence of freezing of gait were recruited. They underwent 24 sessions of video-therapy training based on carefully watching video clips on motor tasks linked to balance, subsequently performing the same observed movements. No statistically significant differences were observed in the identified outcome measures with the Berg Balance Scale and the Activities-Specific Balance Confidence Scale after two months of follow-up. In the present study, a short course of action observation treatment seems to be not effective in reducing balance impairments and postural instability in patients affected by mild to moderate PD. Further studies with larger samples, longer follow-up period, and standardized protocols of action observation treatment are needed to investigate the effects of this rehabilitation technique in the management of postural and balance disorders of PD patients.

A bioequivalence study of two tamsulosin sustained-release tablets in Indonesian healthy volunteers.

Science.gov (United States)

Prasaja, Budi; Harahap, Yahdiana; Lusthom, Windy; Setiawan, Evy C; Ginting, Mena B; Hardiyanti; Lipin

2011-06-01

The bioavailability of two 0.4 mg tamsulosin sustained-release film-coated tablet formulations was compared; using generic tablets (Prostam(®)) as test formulation and the originator product as reference formulation. Twenty-four subjects were included in this single-dose, open-label, randomized two-way crossover design following an overnight fasting. A one-week wash-out period was applied. Blood samples were drawn up to 72 h following drug administration. Plasma concentration of tamsulosin was determined by liquid chromatography-tandem mass spectrometry method with TurboIonSpray mode. Pharmacokinetic parameters AUC(0-t,) AUC(0-∞), C (max) and t (½) were determined and used for bioequivalence evaluation after log-transformation, whereas t (max) ratios were evaluated non-parametrically. The estimated point and 90% confidence intervals (CI) for AUC(0-t,) AUC(0-∞), C (max) and t (½) were 109.55% (96.41-124.49%), 109.94% (96.85-124.81%), 105.87% (92.88-120.67%) and 100.00% (90.56-110.43%), respectively. These results indicated that the two formulations of tamsulosin were bioequivalent; therefore they may be prescribed interchangeably.

Trazodone plus pregabalin combination in the treatment of fibromyalgia: a two-phase, 24-week, open-label uncontrolled study

Directory of Open Access Journals (Sweden)

Rodriguez-Lopez Carmen M

2011-05-01

Full Text Available Abstract Background Although trazodone is frequently used by fibromyalgia patients, its efficacy on this disease has not been adequately studied. If effective, pregabalin, whose beneficial effects on pain and sleep quality in fibromyalgia have been demonstrated, could complement the antidepressant and anxiolytic effects of trazodone. The aim of the present study was to assess the effectiveness of trazodone alone and in combination with pregabalin in the treatment of fibromyalgia. Methods This was an open-label uncontrolled study. Trazodone, flexibly dosed (50-300 mg/day, was administered to 66 fibromyalgia patients during 12 weeks; 41 patients who completed the treatment accepted to receive pregabalin, also flexibly dosed (75-450 mg/day, added to trazodone treatment for an additional 12-week period. Outcome measures included the Fibromyalgia Impact Questionnaire (FIQ, the Pittsburgh Sleep Quality Index (PSQI, the Beck Depression Inventory (BDI, the Hospital Anxiety and Depression Scale (HADS, the Brief Pain Inventory (BPI, the Short-Form Health Survey (SF-36, and the Patients' Global Improvement scale (PGI. Emergent adverse reactions were recorded. Data were analyzed with repeated measures one-way ANOVA and paired Student's t test. Results Treatment with trazodone significantly improved global fibromyalgia severity, sleep quality, and depression, as well as pain interference with daily activities although without showing a direct effect on bodily pain. After pregabalin combination additional and significant improvements were seen on fibromyalgia severity, depression and pain interference with daily activities, and a decrease in bodily pain was also apparent. During the second phase of the study, only two patients dropped out due to side effects. Conclusions Trazodone significantly improved fibromyalgia severity and associated symptomatology. Its combination with pregabalin potentiated this improvement and the tolerability of the drugs in

Tritium labelling of two new analgesic drugs

International Nuclear Information System (INIS)

Santamaria, J.; Rebollo, D.V.; Rivera, P.; Esteban, M.

1986-01-01

The labelling with tritium of two arylpropionic esters was studied. The synthesis between 3 H-Ibuprofen and the two unlabelled alcoholic moieties (Cl-Alkanol and CF 3 -Alkanol) was performed. Assuming that we got ready the acidic moiety, 3 H-Ibuprofen, in our Laboratory, we attempted to label with tritium the alcoholic moiety and then go on to its esterification. Prior to labelling, thermic stability of 2-(4-(3-chlorophenyl)-1-piperazinyl) ethanol (Cl-Alkanol) was studied. As result of this study we had to change the labelling method, so that the Cl-Alkanol was unstable at 70 0 C. Purification was accomplished through thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). Concentration, purity and specific activities of the two labelled compounds were determined by ultraviolet, HPLC and liquid scintillation techniques. (author)

Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

Science.gov (United States)

Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

2013-11-01

An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

Crossover learning of gestures in two ideomotor apraxia patients: A single case experimental design study.

Science.gov (United States)

Shimizu, Daisuke; Tanemura, Rumi

2017-06-01

Crossover learning may aid rehabilitation in patients with neurological disorders. Ideomotor apraxia (IMA) is a common sequela of left-brain damage that comprises a deficit in the ability to perform gestures to verbal commands or by imitation. This study elucidated whether crossover learning occurred in two post-stroke IMA patients without motor paralysis after gesture training approximately 2 months after stroke onset. We quantitatively analysed the therapeutic intervention history and investigated whether revised action occurred during gesture production. Treatment intervention was to examine how to influence improvement and generalisation of the ability to produce the gesture. This study used an alternating treatments single-subject design, and the intervention method was errorless learning. Results indicated crossover learning in both patients. Qualitative analysis indicated that revised action occurred during the gesture-production process in one patient and that there were two types of post-revised action gestures: correct and incorrect gestures. We also discovered that even when a comparably short time had elapsed since stroke onset, generalisation was difficult. Information transfer between the left and right hemispheres of the brain via commissural fibres is important in crossover learning. In conclusion, improvements in gesture-production skill should be made with reference to the left cerebral hemisphere disconnection hypothesis.

An open-label Optional Titration Trial to Evaluate the Efficacy ...

African Journals Online (AJOL)

An eight-week open-label optional titration trial to evaluate the efficacy, tolerability and safety of Valsartan 80 mg/ & 160 mg once daily was carried out in patients with mild to moderate essential hypertension at the Lagos University Teaching Hospital. There was a significant reduction in both systolic and diastolic blood ...

Open-Label Trial of Atomoxetine Hydrochloride in Adults with ADHD

Science.gov (United States)

Johnson, Mats; Cederlund, Mats; Rastam, Maria; Areskoug, Bjorn; Gillberg, Christopher

2010-01-01

Background: While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Methods: Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Results: Ten patients met primary…

Two measures of bilingualism in the memories of immigrants and indigenous minorities: crossover memories and codeswitching.

Science.gov (United States)

Altman, Carmit

2015-04-01

Two indices of bilingualism, crossover memories and codeswitching (CS), were explored in five groups of immigrant (English-Hebrew, Georgian-Hebrew Russian-Hebrew) and indigenous bilinguals (Arabic-Hebrew, Hebrew-English). Participants recalled memories in response to cue words and then were asked to report the language of retrieval and provide a more elaborate narrative. More memories were 'same language' memories, recalled in the language of the experimental session/cue word, but as many as 48 % of the memories were crossovers, i.e. memories reported in a language other than the language of the session/cue word. In an effort to examine the ecological validity of the self-reported language of the memories, the frequency of CS in the elaborated narratives was investigated. For the entire sample, more CS was found for self-reported crossover memories in L2 sessions. In a further analysis of CS in crossover memories, collapsed across L1 and L2 sessions, significant differences emerged between immigrants and indigenous bilinguals. Differences between immigrant and non-immigrant bilinguals are discussed in terms of the role of activation in crossover memories.

Quantum-classical crossover of the escape rate in the two-parameter doubly periodic potential

Energy Technology Data Exchange (ETDEWEB)

Zhou Bin [Department of Physics, Hubei University, Wuhan 430062, Hubei (China)]. E-mail: binzhoucn@yahoo.com

2005-05-09

The transition from the quantum tunneling to classical hopping for a two-parameter doubly periodic potential is investigated. According to the Chudnovsky's criterion for the first-order transition, it is shown that there is the first- or second-order transition depending on different parameters regions. The phase boundary lines between first- and second-order transitions are calculated, and a complete phase diagram is presented.

Quantum-classical crossover of the escape rate in the two-parameter doubly periodic potential

International Nuclear Information System (INIS)

Zhou Bin

2005-01-01

The transition from the quantum tunneling to classical hopping for a two-parameter doubly periodic potential is investigated. According to the Chudnovsky's criterion for the first-order transition, it is shown that there is the first- or second-order transition depending on different parameters regions. The phase boundary lines between first- and second-order transitions are calculated, and a complete phase diagram is presented

Quantum classical crossover of the escape rate in the two-parameter doubly periodic potential

Science.gov (United States)

Zhou, Bin

2005-05-01

The transition from the quantum tunneling to classical hopping for a two-parameter doubly periodic potential is investigated. According to the Chudnovsky's criterion for the first-order transition, it is shown that there is the first- or second-order transition depending on different parameters regions. The phase boundary lines between first- and second-order transitions are calculated, and a complete phase diagram is presented.

Are needle-free injections a useful alternative for growth hormone therapy in children? Safety and pharmacokinetics of growth hormone delivered by a new needle-free injection device compared to a fine gauge needle.

NARCIS (Netherlands)

Dorr, H.G.; Zabransky, S.; Keller, E.; Otten, B.J.; Partsch, C.J.; Nyman, L.; Gillespie, B.K.; Lester, N.R.; Wilson, A.M.; Hyren, C.; Kuijck, M.A. van; Schuld, P.; Schoenfeld, S.L.

2003-01-01

The clinical safety, use and pharmacokinetics of a new needle-free device for delivery of growth hormone (GH) were compared with those of conventional needle injection devices. In an open-label, randomized, 4-period crossover study, 18 healthy adults received single subcutaneous injections of

Pharmacokinetics and pharmacodynamics of various glucagon dosages at different blood glucose levels

NARCIS (Netherlands)

Blauw, H.; Wendl, I.; DeVries, J. H.; Heise, T.; Jax, T.

2016-01-01

To evaluate the pharmacokinetics and pharmacodynamics of different doses of glucagon administered subcutaneously (s.c.) at different blood glucose levels. This study was an open-label, randomized, three-period, cross-over experiment in 6 patients with type 1 diabetes. During each of the three

ROTATION PERIODS OF OPEN-CLUSTER STARS .3.

NARCIS (Netherlands)

PROSSER, CF; SHETRONE, MD; DASGUPTA, A; BACKMAN, DE; LAAKSONEN, BD; BAKER, SW; MARSCHALL, LA; WHITNEY, BA; KUIJKEN, K; STAUFFER, [No Value

We present the results from a photometric monitoring program of 15 open cluster stars and one weak-lined T Tauri star during late 1993/early 1994. Several slow rotators which are members of the Alpha Persei, Pleiades, and Hyades open clusters have been monitored and period estimates derived. Using

An Open-Label Trial of Escitalopram in Pervasive Developmental Disorders.

Science.gov (United States)

Owley, Thomas; Walton, Laura; Salt, Jeff; Guter, Stephen J., Jr.; Winnega, Marrea; Leventhal, Bennett L.; Cook, Edwin H., Jr.

2005-01-01

Objective: To assess the effect of escitalopram in the treatment of pervasive developmental disorders (PDDs). Method: This 10-week study had a forced titration, open-label design. Twenty-eight subjects (mean age 125.1 [+ or -] 33.5 months) with a PDD received escitalopram at a dose that increased weekly to a maximum dose of 20 mg as tolerated. The…

Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder

Science.gov (United States)

Fung, Lawrence K.; Libove, Robin A.; Phillips, Jennifer; Haddad, Francois; Hardan, Antonio Y.

2014-01-01

The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse…

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

Science.gov (United States)

Goadsby, P J; Grosberg, B M; Mauskop, A; Cady, R; Simmons, K A

2014-10-01

We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Sertraline and periodic limb movements during sleep: an 8-week open-label study in depressed patients with insomnia.

Science.gov (United States)

Zhang, Bin; Hao, Yanli; Jia, Fujun; Li, Xueli; Ren, Yanzhen; Zhou, Ping; Liu, Wuhan; Wing, Yun Kwok

2013-12-01

Previous studies have reported that selective serotonin reuptake inhibitors (SSRIs) might induce or exacerbate periodic limb movements during sleep (PLMS). However, most of these studies were retrospective and cross-sectional studies with small sample sizes on a selective SSRI, fluoxetine. Because different SSRIs have different pharmacologic profiles, it was not certain if other SSRIs also might lead to PLMS. Data were taken from an open-label 8-week trial of sertraline in depressive patients with insomnia (n=31). Depressed patients were administered sertraline 50mg at 8:00am on the first day, and the dosage was subsequently titrated up to a maximum of 200mg daily during the 8-week trial. All participants were tested by repeated polysomnography (PSG) (baseline, first day, 14th day, 28th day, and 56th day). Periodic leg movements (PLM) were visually counted and the PLM index (PLMI) was calculated. PLMS was defined as PLMI ⩾5, and significant PLMS was defined as PLMI ⩾15. Compared with baseline (PLMI, 3.6±1.5), all PLMI indices increased on the immediate administration of sertraline on the first day (PLMI, 5.1±3.9). From the 14th day onward, PLMI became stable and significantly higher than baseline and the first day (8.7±3.1 on the 14th day, 8.3±3.7 on the 28th day, and 8.5±3.6 on the 56th day; F[11.81]; P=.003). The clinical responses and PSG characteristics continuously improved during the 8-week trial. The PLMS group (PLMI ⩾5) had a higher arousal index (AI) than the non-PLMS group on the 14th day (9.4±5.5 vs 5.2±3.7; t test, 4.22; P=.03) and the 56th day (8.1±5.5 vs 4.3±3.7; z score, 3.11; P=.04); albeit, there was no significant clinical disturbances in the PLMS group. PLMS were increased during sertraline treatment, but only a few of the PLMS reached the significant level. This effect of sertraline on PLMS might be dosage dependent. Although the sertraline-induced PLMS did not seem to cause significant clinical disturbance, the PLMS group (PLMI �

Multi-modal distribution crossover method based on two crossing segments bounded by selected parents applied to multi-objective design optimization

Energy Technology Data Exchange (ETDEWEB)

Ariyarit, Atthaphon; Kanazaki, Masahiro [Tokyo Metropolitan University, Tokyo (Japan)

2015-04-15

This paper discusses airfoil design optimization using a genetic algorithm (GA) with multi-modal distribution crossover (MMDX). The proposed crossover method creates four segments from four parents, of which two segments are bounded by selected parents and two segments are bounded by one parent and another segment. After these segments are defined, four offsprings are generated. This study applied the proposed optimization to a real-world, multi-objective airfoil design problem using class-shape function transformation parameterization, which is an airfoil representation that uses polynomial function, to investigate the effectiveness of this algorithm. The results are compared with the results of the blend crossover (BLX) and unimodal normal distribution crossover (UNDX) algorithms. The objective of these airfoil design problems is to successfully find the optimal design. The outcome of using this algorithm is superior to that of the BLX and UNDX crossover methods because the proposed method can maintain higher diversity than the BLX and UNDX methods. This advantage is desirable for real-world problems.

Multi-modal distribution crossover method based on two crossing segments bounded by selected parents applied to multi-objective design optimization

International Nuclear Information System (INIS)

Ariyarit, Atthaphon; Kanazaki, Masahiro

2015-01-01

This paper discusses airfoil design optimization using a genetic algorithm (GA) with multi-modal distribution crossover (MMDX). The proposed crossover method creates four segments from four parents, of which two segments are bounded by selected parents and two segments are bounded by one parent and another segment. After these segments are defined, four offsprings are generated. This study applied the proposed optimization to a real-world, multi-objective airfoil design problem using class-shape function transformation parameterization, which is an airfoil representation that uses polynomial function, to investigate the effectiveness of this algorithm. The results are compared with the results of the blend crossover (BLX) and unimodal normal distribution crossover (UNDX) algorithms. The objective of these airfoil design problems is to successfully find the optimal design. The outcome of using this algorithm is superior to that of the BLX and UNDX crossover methods because the proposed method can maintain higher diversity than the BLX and UNDX methods. This advantage is desirable for real-world problems.

Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

DEFF Research Database (Denmark)

Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

2016-01-01

Objectives To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Methods Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retrea...

Morning and evening behavior in children and adolescents treated with atomoxetine once daily for Attention-Deficit/Hyperactivity Disorder (ADHD: Findings from two 24-week, open-label studies

Directory of Open Access Journals (Sweden)

Schacht Alexander

2009-02-01

Full Text Available Abstract Background The impact of once daily atomoxetine treatment on symptoms in children and adolescents with ADHD may vary over the day. In order to capture such variations, two studies were undertaken in children and adolescents with ADHD using two instruments that capture morning and evening behavior and ADHD-related difficulties over the day. This secondary measure analysis builds on two primary analyses that were conducted separately for children and adolescents and also published separately. Methods In two open-label studies, ADHD patients aged 6–17 years (n = 421, received atomoxetine in the morning (target-dose 0.5–1.2 mg/kg/day for up to 24 weeks. Morning and evening behavior was assessed using the investigator-rated Weekly Rating of Evening and Morning Behavior (WREMB-R scale. ADHD-related difficulties at various times of the day (morning, during school, during homework, evening were assessed using the Global Impression of Perceived Difficulties (GIPD scale, rated by patients, parents and physicians. Data from both studies were combined for this secondary measure analysis. Results Both WREMB-R subscores decreased significantly over time, the evening subscore from 13.7 (95% CI 13.2;14.2 at baseline to 8.0 (7.4;8.5 at week 2, the morning subscore from 4.3 (4.0;4.5 to 2.4 (2.2;2.6. Scores then remained stable until week 24. All GIPD items improved correspondingly. At all times of the day, patients rated ADHD-related difficulties as less severe than parents and physicians. Conclusion These findings from two open-label studies suggest that morning and evening behavior and ADHD-related difficulties in the mornings and evenings improve over time with once daily atomoxetine treatment.

Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study.

Science.gov (United States)

Scallion, Ralph; Moore, Keith A

2009-10-01

Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is an investigational formulation that uses dispersing agents designed to facilitate rapid and consistent absorption of this NSAID. The aim of this study was to characterize the effects of food intake on the pharmacokinetic (PK) profile of oral DPSGC at doses of 25 and 50 mg. In this open-label, randomized, single-dose (2 distinct doses), 2-way crossover bioavailability study, healthy adult volunteers were randomly assigned to receive a single dose of DPSGC 25 or 50 mg after an overnight fast (fasted condition) or high-fat breakfast (fed condition) (period 1). After 7 days, the participants received the same dose under the opposite fed/fasted condition (period 2). Serial blood samples were obtained before and through 6 hours after study drug administration. Concentrations of diclofenac in plasma were determined using HPLC, and PK profiles were studied using ANCOVA. Adverse events (AEs) were monitored and recorded on each in-clinic day. Of 47 participants included in the study, 24 received the 25-mg dose of DPSGC and 23 received the 50-mg dose. The majority of participants were male (80.9%), and the mean age was 28.6 years. The mean (SD) AUC values for the fasted and fed states were 691 (195) and 680 (184) ng x h/mL, respectively, with the 25-mg dose, and 1521 (377) and 1416 (366) ng . h/mL, respectively, with the 50-mg dose, suggesting that the extent of absorption was similar with both dietary conditions at each dose. Food intake was associated with decreases in C(max) by nearly half in the 25-mg group (fasted vs fed, 1156 [482] vs 686 [411] ng/mL, respectively; P < 0.05) and the 50-mg group (2365 [1034] vs 1154 [592 ng/mL; P < 0.05) and delayed T(max) in the 25-mg group (0.49 [0.16] vs 1.02 [0.55] hours; P < 0.05) and 50-mg group (0.51 [0.19] vs 1.28 [0.71] hours; P < 0.05). Two mild AEs (nasal congestion and light-headedness) were reported in 2 participants who received 25 mg under fed conditions

An approach to combining parallel and cross-over trials with and without run-in periods using individual patient data.

Science.gov (United States)

Tvete, Ingunn F; Olsen, Inge C; Fagerland, Morten W; Meland, Nils; Aldrin, Magne; Smerud, Knut T; Holden, Lars

2012-04-01

In active run-in trials, where patients may be excluded after a run-in period based on their response to the treatment, it is implicitly assumed that patients have individual treatment effects. If individual patient data are available, active run-in trials can be modelled using patient-specific random effects. With more than one trial on the same medication available, one can obtain a more precise overall treatment effect estimate. We present a model for joint analysis of a two-sequence, four-period cross-over trial (AABB/BBAA) and a three-sequence, two-period active run-in trial (AB/AA/A), where the aim is to investigate the effect of a new treatment for patients with pain due to osteoarthritis. Our approach enables us to separately estimate the direct treatment effect for all patients, for the patients excluded after the active run-in trial prior to randomisation, and for the patients who completed the active run-in trial. A similar model approach can be used to analyse other types of run-in trials, but this depends on the data and type of other trials available. We assume equality of the various carry-over effects over time. The proposed approach is flexible and can be modified to handle other designs. Our results should be encouraging for those responsible for planning cost-efficient clinical development programmes.

The effect of exercise on the absorption of inhaled human insulin in healthy volunteers

DEFF Research Database (Denmark)

Petersen, Astrid Heide; Kohler, Gerd; Korsatko, Stefan

2008-01-01

overall absorption. Aims To investigate the effect of moderate exercise on the absorption of inhaled insulin. Methods A single-centre, randomized, open-label, three-period cross-over trial was carried out in 12 nonsmoking healthy subjects. A dose of 3.5 mg inhaled human insulin was administered via...

Two Responses to Hastings on Labeling.

Science.gov (United States)

Somogyi, Katherine M. M.; And Others

1995-01-01

Two comments respond to an R. P. Hastings article on labeling of individuals with mental retardation. The first comment notes that diagnoses should not be used as labels but as identifications of disorders a person has. The second comment calls for people to come forth with synonyms for "mental retardation" that will not immediately be stigmatic.…

Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial.

Science.gov (United States)

Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

2016-06-07

Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

Influence of pressure and interactions strength on hysteretic behavior in two-dimensional polymeric spin crossover compounds

Energy Technology Data Exchange (ETDEWEB)

Chiruta, Daniel [GEMAC, Université de Versailles Saint-Quentin-en-Yvelines, CNRS-UVSQ (UMR 8635), 78035 Versailles Cedex (France); LISV, Université de Versailles Saint-Quentin-en-Yvelines, 78140 Velizy (France); Faculty of Electrical Engineering and Computer Science, Stefan cel Mare University, 720229 Suceava (Romania); Linares, Jorge [GEMAC, Université de Versailles Saint-Quentin-en-Yvelines, CNRS-UVSQ (UMR 8635), 78035 Versailles Cedex (France); Richard Dahoo, Pierre [LATMOS, Université de Versailles-Saint-Quentin-en-Yvelines, CNRS-UPMC-UVSQ (UMR 8190), 78280 Guyancourt (France); Dimian, Mihai, E-mail: dimian@usv.ro [Faculty of Electrical Engineering and Computer Science, Stefan cel Mare University, 720229 Suceava (Romania)

2014-02-15

A study of thermal behavior for two-dimensional spin-crossover compounds is performed by using an Ising-like model including both short-range and long-range interactions and a Monte Carlo entropic sampling technique for determining the associated density of states. The effects of various factors, such as external pressure, internal interaction strength or system size, on the thermal transition are analyzed and compared to several experimental findings in this area. The study is focused on two-step transitions and the conditions for hysteresis behavior at each step which are especially important for the potential applications of spin-crossover materials in data storage devices or smart sensors.

Ethosuximide for Essential Tremor: An Open-Label Trial

Science.gov (United States)

Gironell, Alexandre; Marin-Lahoz, Juan

2016-01-01

Background T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated. Methods Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID). The main outcome measures were: 1) tremor clinical rating scale (TCRS) score, 2) accelerometric recordings, and 3) self-reported disability scale score. Results Five patients completed the study, and two dropped out due to adverse effects. There were no significant changes in clinical scores in motor task performance (TCRS 1+2), daily living activities (TCRS 3), or in the patients’ subjective assessment (TCRS 4) and global appraisal. There were no differences observed for accelerometry data or disability scale scores. Anxiety, nervousness, headache, and dizziness were reported by two patients while on ethosuximide, causing them to stop the trial. No patient preferred to continue ethosuximide treatment. Discussion The results of our exploratory study suggest that ethosuximide is not an effective treatment for ET. PMID:27625899

Ethosuximide for Essential Tremor: An Open-Label Trial

Directory of Open Access Journals (Sweden)

Alexandre Gironell

2016-07-01

Full Text Available Background: T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated. Methods: Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID. The main outcome measures were: 1 tremor clinical rating scale (TCRS score, 2 accelerometric recordings, and 3 self-reported disability scale score. Results: Five patients completed the study, and two dropped out due to adverse effects. There were no significant changes in clinical scores in motor task performance (TCRS 1+2, daily living activities (TCRS 3, or in the patients’ subjective assessment (TCRS 4 and global appraisal. There were no differences observed for accelerometry data or disability scale scores. Anxiety, nervousness, headache, and dizziness were reported by two patients while on ethosuximide, causing them to stop the trial. No patient preferred to continue ethosuximide treatment. Discussion: The results of our exploratory study suggest that ethosuximide is not an effective treatment for ET.

DRY CUPPING IN CHILDREN WITH FUNCTIONAL CONSTIPATION: A RANDOMIZED OPEN LABEL CLINICAL TRIAL.

Science.gov (United States)

Shahamat, Mahmoud; Daneshfard, Babak; Najib, Khadijeh-Sadat; Dehghani, Seyed Mohsen; Tafazoli, Vahid; Kasalaei, Afshineh

2016-01-01

As a common disease in pediatrics, constipation poses a high burden to the community. In this study, we aimed to investigate the efficacy of dry cupping therapy (an Eastern traditional manipulative therapy) in children with functional constipation. One hundred and twenty children (4-18 years old) diagnosed as functional constipation according to ROME III criteria were assigned to receive a traditional dry cupping protocol on the abdominal wall for 8 minutes every other day or standard laxative therapy (Polyethylene glycol (PEG) 40% solution without electrolyte), 0.4 g/kg once daily) for 4 weeks, in an open label randomized controlled clinical trial using a parallel design with a 1:1 allocation ratio. Patients were evaluated prior to and following 2, 4, 8 and 12 weeks of the intervention commencement in terms of the ROME III criteria for functional constipation. There were no significant differences between the two arms regarding demographic and clinical basic characteristics. After two weeks of the intervention, there was a significant better result in most of the items of ROME III criteria of patients in PEG group. In contrast, after four weeks of the intervention, the result was significantly better in the cupping group. There was no significant difference in the number of patients with constipation after 4 and 8 weeks of the follow-up period. This study showed that dry cupping of the abdominal wall, as a traditional manipulative therapy, can be as effective as standard laxative therapy in children with functional constipation.

Switching from rivaroxaban to warfarin: an open label pharmacodynamic study in healthy subjects

Science.gov (United States)

Moore, Kenneth Todd; Byra, William; Vaidyanathan, Seema; Natarajan, Jaya; Ariyawansa, Jay; Salih, Hiba; Turner, Kenneth C

2015-01-01

Aims The primary objective was to explore the pharmacodynamic changes during transition from rivaroxaban to warfarin in healthy subjects. Safety, tolerability and pharmacokinetics were assessed as secondary objectives. Methods An open label, non-randomized, sequential two period study. In treatment period 1 (TP1), subjects received rivaroxaban 20 mg once daily (5 days), followed by co-administration with a warfarin loading dose regimen of 5 or 10 mg (for the 10 mg regimen, the dose could be uptitrated to attain target international normalized ratio [INR] ≥2.0) once daily (2–4 days). When trough INR values ≥2.0 were attained, rivaroxaban was discontinued and warfarin treatment continued as monotherapy (INR 2.0–3.0). During treatment period 2, subjects received the same warfarin regimen as in TP1, but without rivaroxaban. Results During co-administration, maximum INR and prothrombin time (PT) values were higher than with rivaroxaban or warfarin monotherapy. The mean maximum effect (Emax) for INR after co-administration was 2.79–4.15 (mean PT Emax 41.0–62.7 s), compared with 1.41–1.74 (mean PT Emax 20.1–25.2 s) for warfarin alone. However, rivaroxaban had the smallest effect on INR at trough rivaroxaban concentrations. Neither rivaroxaban nor warfarin significantly affected maximum plasma concentrations of the other drug. Conclusions The combined pharmacodynamic effects during co-administration of rivaroxaban and warfarin were greater than additive, but the pharmacokinetics of both drugs were unaffected. Co-administration was well tolerated. When transitioning from rivaroxaban to warfarin, INR monitoring during co-administration should be performed at the trough rivaroxaban concentration to minimize the effect of rivaroxaban on INR. PMID:25475601

Transdermal granisetron versus palonosetron for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: a multicenter, randomized, open-label, cross-over, active-controlled, and phase IV study.

Science.gov (United States)

Seol, Young Mi; Kim, Hyo Jeong; Choi, Young Jin; Lee, Eun Mi; Kim, Yang Soo; Oh, Sung Yong; Koh, Su Jin; Baek, Jin Ho; Lee, Won Sik; Joo, Young Don; Lee, Hyun Gi; Yun, Eun Young; Chung, Joo Seop

2016-02-01

Palonosetron is the second-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) that has shown better efficacy than the first-generation 5-HT3RA for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC). Granisetron transdermal delivery system (GTDS), a novel transdermal formulation, was developed to deliver granisetron continuously over 7 days. This study compared the efficacy and tolerability of the GTDS to palonosetron for the control of CINV following MEC. A total of 196 patients were randomized to GP or PG group. In this multicenter, randomized, open-label, cross-over, active-controlled, Phase IV study, GP group was assigned to receive transdermal granisetron (one GTDS patch, 7 days) in the first chemotherapy cycle, palonosetron (iv 0.25 mg/day, 1 days) in the second chemotherapy cycle before receiving MEC, and PG group was assigned to receive palonosetron in the first cycle and GTDS in the second cycle. Primary endpoint was the percentage of chemotherapy cycles achieving complete response (CR; defined as no emetic episodes and no rescue medication use) during the acute phase (0-24 h in post-chemotherapy; non-inferiority comparison with palonosetron). Total 333 cycles (165 in GTDS and 168 in palonosetron) were included in the per protocol analysis. The GTDS cycles showed non-inferiority to palonosetron cycles during the acute phase: CR was achieved by 124 (75.2 %) patients in the GTDS cycles and 134 (79.8 %) patients in the palonosetron cycles (treatment difference, -4.6 %; 95 % confidence interval, -13.6-4.4). There was no significant difference in CR rate during acute phase after the end of the first and second chemotherapy cycle between GP and PG group (p = 0.405, p = 0.074). Patients' satisfaction, assessed using Functional Living Index-Emesis (FLI-E), GTDS cycle were higher than those of palonosetron cycle in GP group (FLI-E score; median 1549.5 in GTDS cycle, median 1670

Accumulation of unstable periodic orbits and the stickiness in the two-dimensional piecewise linear map.

Science.gov (United States)

Akaishi, A; Shudo, A

2009-12-01

We investigate the stickiness of the two-dimensional piecewise linear map with a family of marginal unstable periodic orbits (FMUPOs), and show that a series of unstable periodic orbits accumulating to FMUPOs plays a significant role to give rise to the power law correlation of trajectories. We can explicitly specify the sticky zone in which unstable periodic orbits whose stability increases algebraically exist, and find that there exists a hierarchy in accumulating periodic orbits. In particular, the periodic orbits with linearly increasing stability play the role of fundamental cycles as in the hyperbolic systems, which allows us to apply the method of cycle expansion. We also study the recurrence time distribution, especially discussing the position and size of the recurrence region. Following the definition adopted in one-dimensional maps, we show that the recurrence time distribution has an exponential part in the short time regime and an asymptotic power law part. The analysis on the crossover time T(c)(*) between these two regimes implies T(c)(*) approximately -log[micro(R)] where micro(R) denotes the area of the recurrence region.

Methodological adequacy of articles published in two open-access Brazilian cardiology periodicals.

Science.gov (United States)

Macedo, Cristiane Rufino; Silva, Davi Leite da; Puga, Maria Eduarda

2010-01-01

The use of rigorous scientific methods has contributed towards developing scientific articles of excellent methodological quality. This has made it possible to promote their citation and increase the impact factor. Brazilian periodicals have had to adapt to certain quality standards demanded by these indexing organizations, such as the content and the number of original articles published in each issue. This study aimed to evaluate the methodological adequacy of two Brazilian periodicals within the field of cardiology that are indexed in several databases and freely accessible through the Scientific Electronic Library Online (SciELO), and which are now indexed by the Web of Science (Institute for Scientific Information, ISI). Descriptive study at Brazilian Cochrane Center. All the published articles were evaluated according to merit assessment (content) and form assessment (performance). Ninety-six percent of the articles analyzed presented study designs that were adequate for answering the objectives. These two Brazilian periodicals within the field of cardiology published methodologically adequate articles, since they followed the quality standards. Thus, these periodicals can be considered both for consultation and as vehicles for publishing future articles. For further analyses, it is essential to apply other indicators of scientific activity such as bibliometrics, which evaluates quantitative aspects of the production, dissemination and use of information, and scientometrics, which is also concerned with the development of science policies, within which it is often superimposed on bibliometrics.

Safety of telmisartan in patients with arterial hypertension - An open-label observational study

NARCIS (Netherlands)

Michel, Martin C.; Bohner, Herbert; Köster, Jürgen; Schäfers, Rafael; Heemann, Uwe

2004-01-01

Objective: To determine whether age, gender, concomitant disease and/or previous or present antihypertensive medication affect the safety or antihypertensive efficacy of telmisartan in the treatment of arterial hypertension. Study Design and Methods: In this large-scale, open-label postmarketing

Two randomized cross-over trials assessing the impact of dietary gluten or wholegrain on the gut microbiome and host metabolic health

DEFF Research Database (Denmark)

Ibrügger, Sabine; Gøbel, Rikke Juul; Vestergaard, Henrik

2014-01-01

as baseline characteristics of two human intervention studies, within the Gut, Grain and Greens (3G) Center, investigating the effects of a gluten-poor and wholegrain-rich diet on microbiota composition and metabolic health. Design: The gluten and wholegrain studies had a randomized, controlled, cross......-over design each comprising two eight-week dietary intervention periods, separated by a six-week wash-out period. Each trial included 60 men and women exhibiting an increased metabolic risk. In the gluten study a gluten-poor diet was compared with a gluten-rich dietary fiber-controlled diet......, and in the wholegrain study a wholegrain-rich diet was compared with a refined grain diet. The control diet was identical in both studies, being concomitantly high in gluten and refined. Participants substituted all cereal products with provided intervention products which they consumed ad libitum. Before and after...

Bioequivalence of generic lamotrigine 100-mg tablets in healthy Thai male volunteers: a randomized, single-dose, two-period, two-sequence crossover study.

Science.gov (United States)

Srichaiya, Arunee; Longchoopol, Chaowanee; Oo-Puthinan, Sarawut; Sayasathid, Jarun; Sripalakit, Pattana; Viyoch, Jarupa

2008-10-01

Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder. A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers. The aim of this study was to compare the pharmacokinetic parameters between 2 brands of lamotrigine in healthy Thai male volunteers. A randomized, single-dose, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in healthy Thai males. Subjects were randomized to receive either the test or reference formulation in the first period. All subjects were required to be nonsmokers and without a history of alcohol or drug abuse. Plasma samples were collected over a 120-hour period after 100-mg lamotrigine administration in each period. A validated high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products, as defined by the US Food and Drug Administration (FDA), is determined when the ratio for the 90% CIs of the difference in the means of the log-transformed AUC(0-t), AUC(0-infinity), and C(max) of the 2 products are within 0.80 and 1.25. Adverse events were determined by measuring vital signs after dosing. Subjects were also asked if they suffered from undesirable effects such as nausea, vomiting, dizziness, and headache. This bioequivalence study was performed in 24 healthy Thai males (mean [SD] age, 20.5 [1.3] years; range, 19-24 years; weight, 62.5 [7.4] kg; height, 172.8 [6.9] cm; body mass index, 20.9 [2.0] kg/m(2)). The mean (SD) C(max) and T(max) of the test formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.2 (0.9) hours, respectively. The mean (SD) C(max) and T(max) of the reference formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.4 (1.0) hours, respectively. The mean

Pharmacokinetic Profiles of Active Ingredients and Its Metabolites Derived from Rikkunshito, a Ghrelin Enhancer, in Healthy Japanese Volunteers: A Cross-Over, Randomized Study.

Directory of Open Access Journals (Sweden)

Hiroyuki Kitagawa

Full Text Available Rikkunshito, a traditional Japanese (Kampo medicine, has been used to treat upper gastrointestinal disorders such as functional dyspepsia and gastroesophageal reflux. This study investigated the exposure and pharmacokinetics of the ingredients of rikkunshito in healthy volunteers.First, an exploratory nonrandomized, open-label, one-period, noncrossover study using four healthy Japanese volunteers to detect 32 typical ingredients of rikkunshito in plasma and urine. As a result, 18 or 21 of 32 ingredients was detected in plasma or urine samples after oral administration of rikkunshito (7.5 g/day. Furthermore, a randomized, open-label, three-arm, three-period, crossover study using 21 subjects was conducted to determine the amounts of exposure and pharmacokinetic parameters of nine ingredients derived from rikkunshito (atractylodin, atractylodin carboxylic acid, pachymic acid, 3,3',4',5,6,7,8-heptamethoxyflavone, naringenin, nobiletin, liquiritigenin, isoliquiritigenin, and 18β-glycyrrhetinic acid after oral administration of rikkunshito at three different doses (2.5, 5.0, or 7.5 g/day during each period. The pharmacokinetic profiles of the nine ingredients in plasma were characterized. The geometric means (95% confidence interval for the Cmax of the ingredients at a dose of 7.5 g were 1570 (1210-2040, 14,300 (12,200-16,800, 91.0 (71.8-115, 105 (75.6-144, 1150 (802-1650, 35.9 (24.6-52.5, 800 (672-952, 42.8 (30.4-60.3, and 55,600 (39,600-78,100 pg/mL, respectively, and for the AUC0-last were 1760 (1290-2390, 12700 (11,100-14,600, 1210 (882-1650, 225 (157-322, 4630 (2930-7320, 35.7 (20.4-62.7, 4040 (3260-5010, 122 (88.2-168, and 832,000 (628,000-1,100,000 pg·h/mL respectively.We identified the ingredients of rikkunshito that are absorbed in humans. Furthermore, we determined the pharmacokinetics of nine ingredients derived from rikkunshito. This information will be useful for elucidating the pharmacological effects of rikkunshito

Long-Term, Open-Label Safety and Efficacy of Atomoxetine in Adults with ADHD: Final Report of a 4-Year Study

Science.gov (United States)

Adler, Lenard A.; Spencer, Thomas J.; Williams, David W.; Moore, Rodney J.; Michelson, David

2008-01-01

Objective: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. Method: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial…

The Effects of Food Labelling on Postexercise Energy Intake in Sedentary Women.

Science.gov (United States)

Lafrenière, Jacynthe; McNeil, Jessica; Provencher, Véronique; Doucet, Éric

2017-01-01

Food labelling has been previously reported to influence energy intake (EI). Whether food labels influence postexercise EI remains to be determined. We assessed how food labelling and exercise (Ex) interact to influence food perception and postexercise EI. In this randomized crossover design, 14 inactive women participated in 4 experimental conditions: Ex (300 kcal at 70% of VO 2peak ) and lunch labelled as low in fat (LF), Ex and lunch labelled as high in fat (HF), Rest and LF, and Rest and HF. The lunch was composed of a plate of pasta, yogurt, and oatmeal cookies, which had the same nutritional composition across the 4 experimental conditions. EI at lunch and for the 48-hour period covering the testing day and the following day was assessed. Furthermore, perceived healthiness of the meal and appetite ratings were evaluated. There were no effects of exercise and food labelling on EI. However, meals labelled as LF were perceived as heathier, and this label was associated with higher prospective food consumption. Initial beliefs about food items had a stronger effect on healthiness perception than the different food labels and explain the positive correlation with the amount of food consumed ( ρ = 0.34, P < 0.001).

Open-label 24-week extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis.

Science.gov (United States)

2017-10-01

We aimed to explore the longer-term efficacy and safety of edaravone in an active-treatment extension period following the double-blind period of the second phase III study. Patients who met all the following criteria (scores ≥2 points on all 12 items of the revised amyotrophic lateral sclerosis functional rating scale [ALSFRS-R], forced vital capacity ≥80%, definite or probable ALS, and disease duration ≤2 years) were randomised to 60 mg intravenous edaravone or placebo for six cycles in the double-blind period, and then offered the opportunity to proceed to this 24-week open-label extension period. One hundred and twenty-three of 137 patients continued to the extension period: 65 edaravone-edaravone (E-E group) and 58 placebo-edaravone (P-E group). Change (mean ± standard deviation; SD) in the ALSFRS-R score from baseline in the double-blind period was -4.1 ± 3.4 and -6.9 ± 5.1 in the E-E group and P-E group, respectively, while it was -8.0 ± 5.6 in the E-E group and -10.9 ± 6.9 in the P-E group over the whole 48-week period. The ALSFRS-R score changed almost linearly throughout Cycles 1-12 in the E-E group. The most commonly reported adverse events were constipation, dysphagia, and contusion. There was no sudden deterioration in the ALSFRS-R score of the E-E group. No safety concerns related to edaravone were detected.

Helium-air exchange flows through partitioned opening and two-opening

International Nuclear Information System (INIS)

Kang, T. I.

1997-01-01

This paper describes experimental investigations of helium-air exchange flows through partitioned opening and two-opening. Such exchange flows may occur following rupture accident of stand pipe in high temperature engineering test reactor. A test vessel with the two types of small opening on top of test cylinder is used for experiments. An estimation method of mass increment is developed to measure the exchange flow rate. Upward flow of the helium and downward flow of the air in partitioned opening system interact out of entrance and exit of the opening. Therefore, an experiment with two-opening system is made to investigate effect of the fluids interaction of partitioned opening system. As a result of comparison of the exchange flow rates between two types of the opening system, it is demonstrated that the exchange flow rate of the two-opening system is larger than that of the partitioned opening system because of absence of the effect of fluids interaction. (author)

Two-stage crossover from thermal to quantum flux creep of dilute vortex ensembles in various high-Tc superconducting thin films

International Nuclear Information System (INIS)

Akerman, Johan J.; Venturini, E. L.; Siegal, M. P.; Yun, S. H.; Karlsson, U. O.; Rao, K. V.

2001-01-01

The thermal-to-quantum flux creep crossover at low vortex densities has been studied in YBa 2 Cu 3 O 7 , TlBa 2 CaCu 2 O 7-δ , and HgBa 2 CaCu 2 O 6+δ thin films using ac susceptibility. The crossover temperatures T cr are 10--11, 17, and 30 K, respectively. Both thermal and quantum flux creep is suppressed as the vortex density is decreased. We observe a two-stage nature in the crossover behavior which appears to be a general property of all the three materials studied

Catalytic Activity Control via Crossover between Two Different Microstructures

KAUST Repository

Zhou, Yuheng; Zhu, Yihan; Wang, Zhi-Qiang; Zou, Shihui; Ma, Guicen; Xia, Ming; Kong, Xueqian; Xiao, Liping; Gong, Xue-Qing; Fan, Jie

2017-01-01

microstructural control through the crossover between multiply-twinned nanoparticle (MTP) and single crystal (SC) can be readily achieved by solvent post-treatment on gold nanoparticles (AuNPs). Polar solvents (e.g. water, methanol) direct the transformation from

The impact of nurse-driven targeted HIV screening in 8 emergency departments: study protocol for the DICI-VIH cluster-randomized two-period crossover trial.

Science.gov (United States)

Leblanc, Judith; Rousseau, Alexandra; Hejblum, Gilles; Durand-Zaleski, Isabelle; de Truchis, Pierre; Lert, France; Costagliola, Dominique; Simon, Tabassome; Crémieux, Anne-Claude

2016-02-01

In 2010, to reduce late HIV diagnosis, the French national health agency endorsed non-targeted HIV screening in health care settings. Despite these recommendations, non-targeted screening has not been implemented and only physician-directed diagnostic testing is currently performed. A survey conducted in 2010 in 29 French Emergency Departments (EDs) showed that non-targeted nurse-driven screening was feasible though only a few new HIV diagnoses were identified, predominantly among high-risk groups. A strategy targeting high-risk groups combined with current practice could be shown to be feasible, more efficient and cost-effective than current practice alone. DICI-VIH (acronym for nurse-driven targeted HIV screening) is a multicentre, cluster-randomized, two-period crossover trial. The primary objective is to compare the effectiveness of 2 strategies for diagnosing HIV among adult patients visiting EDs: nurse-driven targeted HIV screening combined with current practice (physician-directed diagnostic testing) versus current practice alone. Main secondary objectives are to compare access to specialist consultation and how early HIV diagnosis occurs in the course of the disease between the 2 groups, and to evaluate the implementation, acceptability and cost-effectiveness of nurse-driven targeted screening. The 2 strategies take place during 2 randomly assigned periods in 8 EDs of metropolitan Paris, where 42 % of France's new HIV patients are diagnosed every year. All patients aged 18 to 64, not presenting secondary to HIV exposure are included. During the intervention period, patients are invited to fill a 7-item questionnaire (country of birth, sexual partners and injection drug use) in order to select individuals who are offered a rapid test. If the rapid test is reactive, a follow-up visit with an infectious disease specialist is scheduled within 72 h. Assuming an 80 % statistical power and a 5 % type 1 error, with 1.04 and 3.38 new diagnoses per 10,000 patients in

Methylphenidate, cognition, and epilepsy: A 1-month open-label trial.

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Adams, Jesse; Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J; Loring, David W; Meador, Kimford J

2017-12-01

Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well-validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention-deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open-label follow-up to a double-blind, placebo-controlled, single-dose study. Thirty epilepsy patients entered a 1-month open-label methylphenidate trial after a double-blind phase. Doses were titrated according to clinical practice and patient tolerance, ranging 20-40 mg/day. Primary measures included: Conners' Continuous Performance Test (CPT), Symbol-Digit Modalities Test (SDMT), and Medical College of Georgia Memory Test (MCG). Secondary measures were: Beck Depression Inventory, 2nd Edition (BDI-II), Beck Anxiety Inventory, Apathy Evaluation Scale (AES), Stimulant Side-Effect Checklist, Adverse Events Profile, Quality of Life in Epilepsy-89 (QOLIE-89), and seizure frequency. Fourteen healthy, nonmedicated controls were tested concurrently. Twenty-eight participants with epilepsy (13 men/15 women) completed the trial. Withdrawals occurred due to anxiety (n = 1) and fatigue (n = 1). Mean age was 36.4 years (range = 20-60). Epilepsy types were: focal (n = 21), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.3 years. Mean baseline seizure frequency was 2.8/month. There were significant improvements on methylphenidate for SDMT, MCG, CPT (the ability to discriminate between targets and nontargets [d'] hits, hit reaction time standard deviation, omissions, and commissions), and QOLIE subscales (energy/fatigue, attention/concentration, memory, and language; paired t tests; p ≤ 0.002). BDI-II and additional subscales also improved, at a lower level of statistical significance. Effect

Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema - An open-label randomized controlled trial of efficacy

NARCIS (Netherlands)

van Coevorden, AM; Kamphof, WG; van Sonderen, E; Bruynzeel, DP; Coenraads, PJ

2004-01-01

Objective: To study whether oral psoralen-UV-A (PUVA) with a portable tanning unit at home is as effective as hospital-administered bath PUVA in patients with chronic hand eczema. Design: Open-label randomized controlled trial, with a 10-week treatment period and an 8-week follow-up period. Setting:

EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

Science.gov (United States)

Berlin, Michael S; Rowe-Rendleman, Cheryl; Ahmed, Ike; Ross, Douglas T; Fujii, Akifumi; Ouchi, Takafumi; Quach, Christine; Wood, Andrew; Ward, Caroline L

2016-01-01

Background/aims The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering. Methods This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability. Results Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of −7.4 mm Hg (−30.8%) for AM dosing and −9.1 mm Hg, (−38.0%) for PM dosing; after 14 days, mean reduction in IOP was −6.8 mm Hg (−28.6%) for AM dosing and −7.5 mm Hg (−31.0%) for PM dosing. Conclusions PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP. Trial registration number NCT01670266. PMID:26453641

MTN-001: randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments.

Directory of Open Access Journals (Sweden)

Craig W Hendrix

Full Text Available Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP for human immunodeficiency virus (HIV infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development.MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design.We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both. Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001. Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001. Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03.Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir

A prospective, double-blind, randomized, two-period crossover, multicenter study to evaluate tolerability and patient preference between mirabegron and tolterodine in patients with overactive bladder (PREFER study).

Science.gov (United States)

Staskin, David; Herschorn, Sender; Fialkov, Jonathan; Tu, Le Mai; Walsh, Terry; Schermer, Carol R

2018-02-01

The objective of this study was to assess the tolerability and treatment preference in patients with overactive bladder (OAB) treated with mirabegron or tolterodine. This was a two-period, 8-week crossover, double-blind, phase IV study (PREFER; NCT02138747) in treatment-naive adults with OAB for 3 months or longer randomized to one of four treatment sequences in a 5:5:1:1 ratio (mirabegron/tolterodine, tolterodine/mirabegron, mirabegron/mirabegron, or tolterodine/tolterodine), separated by a washout period of 2 weeks. The primary endpoint was drug tolerability using the Medication Tolerability scale of the OAB Treatment Satisfaction (OAB-S) questionnaire at end of treatment (EoT). Period-by-treatment interactions were analyzed to determine any effect of drug order. Patient preference, change from baseline in OAB symptoms, and treatment-emergent adverse events (TEAEs) were assessed. A total of 358 randomized patients completed the OAB-S Medication Tolerability scale questionnaire at one or more visits after the baseline evaluation. The mean (95% CI) OAB-S Medication Tolerability scores were significantly higher (better tolerability) for mirabegron (86.29 [83.50, 89.08]) than for tolterodine (83.40 [80.59, 86.20]; p = 0.004). The period-by-treatment interaction was not significant (p = 0.955). Improvements in OAB-S Medication Tolerability scores at EoT were more evident in women, patients aged ≥65 years, and in patients without baseline incontinence, and were greater with mirabegron than with tolterodine extended release. There were no significant differences in patient preference or improvements in OAB symptoms. Significant differences in favor of mirabegron were observed for anticholinergic TEAEs (20.4% vs. 27.4%; p = 0.042) and specifically for gastrointestinal disorders (14.7% vs. 22.5%; p = 0.015). Tolerability of mirabegron was significantly higher than that of tolterodine, and patient preference and improvements in OAB symptoms were comparable

Crossover from incoherent to coherent phonon scattering in epitaxial oxide superlattices.

Science.gov (United States)

Ravichandran, Jayakanth; Yadav, Ajay K; Cheaito, Ramez; Rossen, Pim B; Soukiassian, Arsen; Suresha, S J; Duda, John C; Foley, Brian M; Lee, Che-Hui; Zhu, Ye; Lichtenberger, Arthur W; Moore, Joel E; Muller, David A; Schlom, Darrell G; Hopkins, Patrick E; Majumdar, Arun; Ramesh, Ramamoorthy; Zurbuchen, Mark A

2014-02-01

Elementary particles such as electrons or photons are frequent subjects of wave-nature-driven investigations, unlike collective excitations such as phonons. The demonstration of wave-particle crossover, in terms of macroscopic properties, is crucial to the understanding and application of the wave behaviour of matter. We present an unambiguous demonstration of the theoretically predicted crossover from diffuse (particle-like) to specular (wave-like) phonon scattering in epitaxial oxide superlattices, manifested by a minimum in lattice thermal conductivity as a function of interface density. We do so by synthesizing superlattices of electrically insulating perovskite oxides and systematically varying the interface density, with unit-cell precision, using two different epitaxial-growth techniques. These observations open up opportunities for studies on the wave nature of phonons, particularly phonon interference effects, using oxide superlattices as model systems, with extensive applications in thermoelectrics and thermal management.

Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

Science.gov (United States)

McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

2011-01-01

Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

Two efficient label-equivalence-based connected-component labeling algorithms for 3-D binary images.

Science.gov (United States)

He, Lifeng; Chao, Yuyan; Suzuki, Kenji

2011-08-01

Whenever one wants to distinguish, recognize, and/or measure objects (connected components) in binary images, labeling is required. This paper presents two efficient label-equivalence-based connected-component labeling algorithms for 3-D binary images. One is voxel based and the other is run based. For the voxel-based one, we present an efficient method of deciding the order for checking voxels in the mask. For the run-based one, instead of assigning each foreground voxel, we assign each run a provisional label. Moreover, we use run data to label foreground voxels without scanning any background voxel in the second scan. Experimental results have demonstrated that our voxel-based algorithm is efficient for 3-D binary images with complicated connected components, that our run-based one is efficient for those with simple connected components, and that both are much more efficient than conventional 3-D labeling algorithms.

Quantitative monitoring of two simultaneously binding species using Label-Enhanced surface plasmon resonance.

Science.gov (United States)

Eng, Lars; Garcia, Brandon L; Geisbrecht, Brian V; Hanning, Anders

2018-02-26

Surface plasmon resonance (SPR) is a well-established method for biomolecular interaction studies. SPR monitors the binding of molecules to a solid surface, embodied as refractive index changes close to the surface. One limitation of conventional SPR is the universal nature of the detection that results in an inability to qualitatively discriminate between different binding species. Furthermore, it is impossible to directly discriminate two species simultaneously binding to different sites on a protein, which limits the utility of SPR, for example, in the study of allosteric binders or bi-specific molecules. It is also impossible in principle to discriminate protein conformation changes from actual binding events. Here we demonstrate how Label-Enhanced SPR can be utilized to discriminate and quantitatively monitor the simultaneous binding of two different species - one dye-labeled and one unlabeled - on a standard, single-wavelength SPR instrument. This new technique increases the versatility of SPR technology by opening up application areas where the usefulness of the approach has previously been limited. Copyright © 2018 Elsevier Inc. All rights reserved.

Study for every other day administration of vonoprazan in maintenance treatment of erosive GERD: study protocol for a multicentre randomised cross-over study.

Science.gov (United States)

Kato, Mototsugu; Ito, Noriko; Demura, Mamiko; Kubo, Kimitoshi; Mabe, Katsuhiro; Harada, Naohiko

2018-01-01

The first drug selected for treatment of gastro-oesophageal reflux disease (GERD) and prevention of the recurrence is a proton pump inhibitor (PPI), but recently, a potassium-competitive acid blocker (P-CAB) was put on the market in Japan. Its onset of effect is faster than PPI, and it takes more than 2 days to recover acid secretion after the withdrawal period. Therefore, unlike PPI, the usefulness of every other day administration or discontinuous administration is expected. This study is a prospective, multicentre, open-label, two-period randomised cross-over study to compare the efficacy and safety of PPI every other day administration and P-CAB every other day administration in 120 patients who receive erosive GERD maintenance therapy with PPI. Patients will be randomly allocated to receive 4 weeks P-CAB or PPI followed by 4 weeks cross over, where those on P-CAB will receive PPI and vice versa. The primary endpoint is proportion of asymptomatic patients. Secondary endpoints are suppressive effect of GERD symptoms, proportion of asymptomatic patients at each time point, safety and cost-saving effect of P-CAB every other day administration, compliance with every other day administration, and proportion of asymptomatic patients at the first month of study drug administration. This study was approved by the National Hospital Organization Central Review Board for Clinical Trials (5 December 2017). If P-CAB every other day administration is established as one of GERD maintenance therapies, there is merit in both medical cost reduction and the safety to alleviate elevation in serum gastrin. UMIN000034701.

Cyclic labellings with constraints at two distances

OpenAIRE

Leese, R; Noble, S D

2004-01-01

Motivated by problems in radio channel assignment, we consider the vertex-labelling of graphs with non-negative integers. The objective is to minimise the span of the labelling, subject to constraints imposed at graph distances one and two. We show that the minimum span is (up to rounding) a piecewise linear function of the constraints, and give a complete specification, together with associated optimal assignments, for trees and cycles.

A Comparison of Regular Consumption of Fresh Lean Pork, Beef and Chicken on Body Composition: A Randomized Cross-Over Trial

Directory of Open Access Journals (Sweden)

Karen J. Murphy

2014-02-01

Full Text Available Pork is the most widely eaten meat in the world and recent evidence shows that diets high in pork protein, with and without energy restriction, may have favourable effects on body composition. However, it is unclear whether these effects on body composition are specific to pork or whether consumption of other high protein meat diets may have the same benefit. Therefore we aimed to compare regular consumption of pork, beef and chicken on indices of adiposity. In a nine month randomised open-labelled cross-over intervention trial, 49 overweight or obese adults were randomly assigned to consume up to 1 kg/week of pork, chicken or beef, in an otherwise unrestricted diet for three months, followed by two further three month periods consuming each of the alternative meat options. BMI and waist/hip circumference were measured and body composition was determined using dual energy x-ray absorptiometry. Dietary intake was assessed using three day weighed food diaries. Energy expenditure was estimated from activity diaries. There was no difference in BMI or any other marker of adiposity between consumption of pork, beef and chicken diets. Similarly there were no differences in energy or nutrient intakes between diets. After three months, regular consumption of lean pork meat as compared to that of beef and chicken results in similar changes in markers of adiposity of overweight and obese Australian middle-aged men and women.

A Comparison of Regular Consumption of Fresh Lean Pork, Beef and Chicken on Body Composition: A Randomized Cross-Over Trial

Science.gov (United States)

Murphy, Karen J.; Parker, Barbara; Dyer, Kathryn A.; Davis, Courtney R.; Coates, Alison M.; Buckley, Jonathan D.; Howe, Peter R. C.

2014-01-01

Pork is the most widely eaten meat in the world and recent evidence shows that diets high in pork protein, with and without energy restriction, may have favourable effects on body composition. However, it is unclear whether these effects on body composition are specific to pork or whether consumption of other high protein meat diets may have the same benefit. Therefore we aimed to compare regular consumption of pork, beef and chicken on indices of adiposity. In a nine month randomised open-labelled cross-over intervention trial, 49 overweight or obese adults were randomly assigned to consume up to 1 kg/week of pork, chicken or beef, in an otherwise unrestricted diet for three months, followed by two further three month periods consuming each of the alternative meat options. BMI and waist/hip circumference were measured and body composition was determined using dual energy x-ray absorptiometry. Dietary intake was assessed using three day weighed food diaries. Energy expenditure was estimated from activity diaries. There was no difference in BMI or any other marker of adiposity between consumption of pork, beef and chicken diets. Similarly there were no differences in energy or nutrient intakes between diets. After three months, regular consumption of lean pork meat as compared to that of beef and chicken results in similar changes in markers of adiposity of overweight and obese Australian middle-aged men and women. PMID:24534884

Study of open systems with molecules in isotropic liquids

Science.gov (United States)

Kondo, Yasushi; Matsuzaki, Masayuki

2018-05-01

We are interested in dynamics of a system in an environment, or an open system. Such phenomena as crossover from Markovian to non-Markovian relaxation and thermal equilibration are of our interest. Open systems have experimentally been studied with ultra cold atoms, ions in traps, optics, and cold electric circuits because well-isolated systems can be prepared here and thus the effects of environments can be controlled. We point out that some molecules solved in isotropic liquid are well isolated and thus they can also be employed for studying open systems in Nuclear Magnetic Resonance (NMR) experiments. First, we provide a short review on related phenomena of open systems that helps readers to understand our motivation. We, then, present two experiments as examples of our approach with molecules in isotropic liquids. Crossover from Markovian to non-Markovian relaxation was realized in one NMR experiment, while relaxation-like phenomena were observed in approximately isolated systems in the other.

Evolution of open magnetic structures on the sun: the Skylab period

International Nuclear Information System (INIS)

Levine, R.H.

1977-01-01

High-resolution harmonic analysis of the measured photospheric magnetic field of the Sun is used to construct models of open magnetic structures over a period of 11 solar rotations. The models successfully reproduce the surface location and topology of all coronal holes during the Skylab period. In addition, there is persistent evidence in the models that open field lines are associated with active regions in a systematic way. These associations are listed for the period studied; they suggest that open field lines are a basic feature of solar magnetism. Specific examples of the evolution of coronal holes and of calculated open structures are presented. Quantitative study of the measured field strength within and neighboring a hole confirms the fact that coronal hole regions are indistinguishable by local magnetic properties. However, the calculated field strengths at the footpoints of open field lines within coronal holes show distinct evolutionary patterns and may indicate that, at least in young coronal holes, a significant amount of magnetic flux is closed. Problems of studying magnetic field divergence by using these models are discussed

Two- to three-dimensional crossover in a dense electron liquid in silicon

Science.gov (United States)

Matmon, Guy; Ginossar, Eran; Villis, Byron J.; Kölker, Alex; Lim, Tingbin; Solanki, Hari; Schofield, Steven R.; Curson, Neil J.; Li, Juerong; Murdin, Ben N.; Fisher, Andrew J.; Aeppli, Gabriel

2018-04-01

Doping of silicon via phosphine exposures alternating with molecular beam epitaxy overgrowth is a path to Si:P substrates for conventional microelectronics and quantum information technologies. The technique also provides a well-controlled material for systematic studies of two-dimensional lattices with a half-filled band. We show here that for a dense (ns=2.8 ×1014 cm-2) disordered two-dimensional array of P atoms, the full field magnitude and angle-dependent magnetotransport is remarkably well described by classic weak localization theory with no corrections due to interaction. The two- to three-dimensional crossover seen upon warming can also be interpreted using scaling concepts developed for anistropic three-dimensional materials, which work remarkably except when the applied fields are nearly parallel to the conducting planes.

Shelf Life of Food Products: From Open Labeling to Real-Time Measurements.

Science.gov (United States)

Corradini, Maria G

2018-03-25

The labels currently used on food and beverage products only provide consumers with a rough guide to their expected shelf lives because they assume that a product only experiences a limited range of predefined handling and storage conditions. These static labels do not take into consideration conditions that might shorten a product's shelf life (such as temperature abuse), which can lead to problems associated with food safety and waste. Advances in shelf-life estimation have the potential to improve the safety, reliability, and sustainability of the food supply. Selection of appropriate kinetic models and data-analysis techniques is essential to predict shelf life, to account for variability in environmental conditions, and to allow real-time monitoring. Novel analytical tools to determine safety and quality attributes in situ coupled with modern tracking technologies and appropriate predictive tools have the potential to provide accurate estimations of the remaining shelf life of a food product in real time. This review summarizes the necessary steps to attain a transition from open labeling to real-time shelf-life measurements.

Omega-3 fatty acid monotherapy for pediatric bipolar disorder: a prospective open-label trial.

Science.gov (United States)

Wozniak, Janet; Biederman, Joseph; Mick, Eric; Waxmonsky, James; Hantsoo, Liisa; Best, Catherine; Cluette-Brown, Joanne E; Laposata, Michael

2007-01-01

To test the effectiveness and safety of omega-3 fatty acids (Omegabrite(R) brand) in the treatment of pediatric bipolar disorder (BPD). Subjects (N=20) were outpatients of both sexes, 6 to 17 years of age, with a DSM-IV diagnosis of BPD and Young Mania Rating Scale (YMRS) score of >15 treated over an 8-week period in open-label trial with omega-3 fatty acids 1290 mg-4300 mg combined EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Subjects experienced a statistically significant but modest 8.9+/-2.9 point reduction in the YMRS scores (baseline YMRS=28.9+/-10.1; endpoint YMRS=19.1+/-2.6, pDHA increased in treated subjects. As only 35% of these subjects had a response by the usual accepted criteria of >50% decrease on the YMRS, omega-3 fatty acids treatment was associated with a very modest improvement in manic symptoms in children with BPD.

An open-label study of sodium oxybate in Spasmodic dysphonia.

Science.gov (United States)

Rumbach, Anna F; Blitzer, Andrew; Frucht, Steven J; Simonyan, Kristina

2017-06-01

Spasmodic dysphonia (SD) is a task-specific laryngeal dystonia that affects speech production. Co-occurring voice tremor (VT) often complicates the diagnosis and clinical management of SD. Treatment of SD and VT is largely limited to botulinum toxin injections into laryngeal musculature; other pharmacological options are not sufficiently developed. Open-label study. We conducted an open-label study in 23 SD and 22 SD/VT patients to examine the effects of sodium oxybate (Xyrem), an oral agent with therapeutic effects similar to those of alcohol in these patients. Blinded randomized analysis of voice and speech samples assessed symptom improvement before and after drug administration. Sodium oxybate significantly improved voice symptoms (P = .001) primarily by reducing the number of SD-characteristic voice breaks and severity of VT. Sodium oxybate further showed a trend for improving VT symptoms (P = .03) in a subset of patients who received successful botulinum toxin injections for the management of their SD symptoms. The drug's effects were observed approximately 30 to 40 minutes after its intake and lasted about 3.5 to 4 hours. Our study demonstrated that sodium oxybate reduced voice symptoms in 82.2% of alcohol-responsive SD patients both with and without co-occurring VT. Our findings suggest that the therapeutic mechanism of sodium oxybate in SD and SD/VT may be linked to that of alcohol, and as such, sodium oxybate might be beneficial for alcohol-responsive SD and SD/VT patients. 4 Laryngoscope, 127:1402-1407, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Open-label administration of lisdexamfetamine dimesylate improves executive function impairments and symptoms of attention-deficit/hyperactivity disorder in adults.

Science.gov (United States)

Brown, Thomas E; Brams, Matthew; Gao, Joseph; Gasior, Maria; Childress, Ann

2010-09-01

Executive function (EF) impairment in attention-deficit/hyperactivity disorder (ADHD) may account for behavioral symptoms such as poor concentration, impaired working memory, problems in shifting among tasks, and prioritizing and planning complex sets of tasks or completing long-term projects at work or school. Poor self-regulation and control of emotional behaviors frequently are seen in patients with ADHD. This study assessed EF behaviors in adults with ADHD at baseline and after 4 weeks of treatment with lisdexamfetamine dimesylate (LDX). Executive function behavior was assessed using the Brown Attention-Deficit Disorder Scale (BADDS) during the 4-week open-label dose-optimization phase prior to a 2-period, randomized, double-blind, placebo-controlled crossover study of LDX (30-70 mg/day). The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts assessed ADHD symptoms. Change in EF behavioral symptoms was evaluated based on week 4 BADDS total and cluster scores; analyses of shifts from baseline among subjects with BADDS scores < 50, 50 to 59, 60 to 69, and ≥ 70; and scores less than or greater than baseline 90% confidence range (eg, reliably improved or worsened, respectively). Treatment-emergent adverse events (TEAEs) were described. At week 4, BADDS total and cluster scores were reduced (ie, improved; all P < 0.0001 vs baseline [n = 127]). The ADHD-RS-IV with adult prompts scores also improved (all P < 0.0001 vs baseline). At week 4, 62.7% of subjects had a BADDS total score of < 50, and 78.9% were reliably improved; 1.4% were reliably worsened. Common TEAEs (≥ 5%) during the dose-optimization phase were decreased appetite (36.6%), dry mouth (30.3%), headache (19.7%), insomnia (18.3%), upper respiratory tract infection (9.9%), irritability (8.5%), nausea (7.7%), anxiety (5.6%), and feeling jittery (5.6%). Clinically optimized doses of LDX (30-70 mg/day) significantly improved EF behaviors in adults with ADHD. Treatment-emergent adverse events with LDX were

Electroconvulsive therapy for the treatment of clozapine nonresponders suffering from schizophrenia--an open label study

NARCIS (Netherlands)

Kho, K. H.; Blansjaar, B. A.; de Vries, S.; Babuskova, D.; Zwinderman, A. H.; Linszen, D. H.

2004-01-01

OBJECTIVE: This open label study describes the efficacy of electroconvulsive therapy (ECT) as adjunctive treatment in clozapine nonresponders suffering from schizophrenia. METHOD: The results of clozapine and ECT treatment in 11 clozapine nonresponders suffering from schizophrenia are reported in

The Effects of Food Labelling on Postexercise Energy Intake in Sedentary Women

OpenAIRE

Lafrenière, Jacynthe; McNeil, Jessica; Provencher, Véronique; Doucet, Éric

2017-01-01

Food labelling has been previously reported to influence energy intake (EI). Whether food labels influence postexercise EI remains to be determined. We assessed how food labelling and exercise (Ex) interact to influence food perception and postexercise EI. In this randomized crossover design, 14 inactive women participated in 4 experimental conditions: Ex (300?kcal at 70% of VO2peak) and lunch labelled as low in fat (LF), Ex and lunch labelled as high in fat (HF), Rest and LF, and Rest and HF...

Use of the learning conversation improves instructor confidence in life support training: An open randomised controlled cross-over trial comparing teaching feedback mechanisms.

Science.gov (United States)

Baldwin, Lydia J L; Jones, Christopher M; Hulme, Jonathan; Owen, Andrew

2015-11-01

Feedback is vital for the effective delivery of skills-based education. We sought to compare the sandwich technique and learning conversation structured methods of feedback delivery in competency-based basic life support (BLS) training. Open randomised crossover study undertaken between October 2014 and March 2015 at the University of Birmingham, United Kingdom. Six-hundred and forty healthcare students undertaking a European Resuscitation Council (ERC) BLS course were enrolled, each of whom was randomised to receive teaching using either the sandwich technique or the learning conversation. Fifty-eight instructors were randomised to initially teach using either the learning conversation or sandwich technique, prior to crossing-over and teaching with the alternative technique after a pre-defined time period. Outcome measures included skill acquisition as measured by an end-of-course competency assessment, instructors' perception of teaching with each feedback technique and candidates' perception of the feedback they were provided with. Scores assigned to use of the learning conversation by instructors were significantly more favourable than for the sandwich technique across all but two assessed domains relating to instructor perception of the feedback technique, including all skills-based domains. No difference was seen in either assessment pass rates (80.9% sandwich technique vs. 77.2% learning conversation; OR 1.2, 95% CI 0.85-1.84; p=0.29) or any domain relating to candidates' perception of their teaching technique. This is the first direct comparison of two feedback techniques in clinical medical education using both quantitative and qualitative methodology. The learning conversation is preferred by instructors providing competency-based life support training and is perceived to favour skills acquisition. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The BCS-BEC crossover: From ultra-cold Fermi gases to nuclear systems

Science.gov (United States)

Strinati, Giancarlo Calvanese; Pieri, Pierbiagio; Röpke, Gerd; Schuck, Peter; Urban, Michael

2018-04-01

This report addresses topics and questions of common interest in the fields of ultra-cold gases and nuclear physics in the context of the BCS-BEC crossover. By this crossover, the phenomena of Bardeen-Cooper-Schrieffer (BCS) superfluidity and Bose-Einstein condensation (BEC), which share the same kind of spontaneous symmetry breaking, are smoothly connected through the progressive reduction of the size of the fermion pairs involved as the fundamental entities in both phenomena. This size ranges, from large values when Cooper pairs are strongly overlapping in the BCS limit of a weak inter-particle attraction, to small values when composite bosons are non-overlapping in the BEC limit of a strong inter-particle attraction, across the intermediate unitarity limit where the size of the pairs is comparable with the average inter-particle distance. The BCS-BEC crossover has recently been realized experimentally, and essentially in all of its aspects, with ultra-cold Fermi gases. This realization, in turn, has raised the interest of the nuclear physics community in the crossover problem, since it represents an unprecedented tool to test fundamental and unanswered questions of nuclear many-body theory. Here, we focus on the several aspects of the BCS-BEC crossover, which are of broad joint interest to both ultra-cold Fermi gases and nuclear matter, and which will likely help to solve in the future some open problems in nuclear physics (concerning, for instance, neutron stars). Similarities and differences occurring in ultra-cold Fermi gases and nuclear matter will then be emphasized, not only about the relative phenomenologies but also about the theoretical approaches to be used in the two contexts. Common to both contexts is the fact that at zero temperature the BCS-BEC crossover can be described at the mean-field level with reasonable accuracy. At finite temperature, on the other hand, inclusion of pairing fluctuations beyond mean field represents an essential ingredient

Diffusionless phase transition with two order parameters in spin-crossover solids

Energy Technology Data Exchange (ETDEWEB)

Gudyma, Iurii, E-mail: yugudyma@gmail.com; Ivashko, Victor [Department of General Physics, Chernivtsi National University, 58012 Chernivtsi (Ukraine); Linares, Jorge [Groupe d' Etude de la Matière Condensée (GEMAC), UMR 8635, CNRS, Université de Versailles Saint Quentin, 45 avenue des Etats-Unis, 78035 Versailles (France)

2014-11-07

The quantitative analysis of the interface boundary motion between high-spin and low-spin phases is presented. The nonlinear effect of the switching front rate on the temperature is shown. A compressible model of spin-crossover solid is studied in the framework of the Ising-like model with two-order parameters under statistical approach, where the effect of elastic strain on interaction integral is considered. These considerations led to examination of the relation between the order parameters during temperature changes. Starting from the phenomenological Hamiltonian, entropy has been derived using the mean field approach. Finally, the phase diagram, which characterizes the system, is numerically analyzed.

Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS)

DEFF Research Database (Denmark)

Pauls, Mathilde M H; Clarke, Natasha; Trippier, Sarah

2017-01-01

vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. METHODS/DESIGN: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double......-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. SAMPLE SIZE: 54 participants are required to detect a 15% increase in cerebral blood...

Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension.

Science.gov (United States)

Richeldi, Luca; Kreuter, Michael; Selman, Moisés; Crestani, Bruno; Kirsten, Anne-Marie; Wuyts, Wim A; Xu, Zuojun; Bernois, Katell; Stowasser, Susanne; Quaresma, Manuel; Costabel, Ulrich

2017-10-09

The TOMORROW trial of nintedanib comprised a randomised, placebo-controlled, 52-week period followed by a further blinded treatment period and an open-label extension. We assessed outcomes across these periods in patients randomised to nintedanib 150 mg twice daily or placebo at the start of TOMORROW. The annual rate of decline in FVC was -125.4 mL/year (95% CI -168.1 to -82.7) in the nintedanib group and -189.7 mL/year (95% CI -229.8 to -149.6) in the comparator group. The adverse event profile of nintedanib remained consistent throughout the studies. These results support a benefit of nintedanib on slowing progression of idiopathic pulmonary fibrosis beyond 52 weeks. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study.

Science.gov (United States)

Gidal, Barry E; Wechsler, Robert T; Sankar, Raman; Montouris, Georgia D; White, H Steve; Cloyd, James C; Kane, Mary Clare; Peng, Guangbin; Tworek, David M; Shen, Vivienne; Isojarvi, Jouko

2016-10-25

To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg -1 ·d -1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg -1 ·d -1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. NCT00518713 and NCT01160770. This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. © 2016 American Academy of Neurology.

Contrasted patterns of crossover and non-crossover at Arabidopsis thaliana meiotic recombination hotspots.

Directory of Open Access Journals (Sweden)

Jan Drouaud

2013-11-01

Full Text Available The vast majority of meiotic recombination events (crossovers (COs and non-crossovers (NCOs cluster in narrow hotspots surrounded by large regions devoid of recombinational activity. Here, using a new molecular approach in plants, called "pollen-typing", we detected and characterized hundreds of CO and NCO molecules in two different hotspot regions in Arabidopsis thaliana. This analysis revealed that COs are concentrated in regions of a few kilobases where their rates reach up to 50 times the genome average. The hotspots themselves tend to cluster in regions less than 8 kilobases in size with overlapping CO distribution. Non-crossover (NCO events also occurred in the two hotspots but at very different levels (local CO/NCO ratios of 1/1 and 30/1 and their track lengths were quite small (a few hundred base pairs. We also showed that the ZMM protein MSH4 plays a role in CO formation and somewhat unexpectedly we also found that it is involved in the generation of NCOs but with a different level of effect. Finally, factors acting in cis and in trans appear to shape the rate and distribution of COs at meiotic recombination hotspots.

Effects of the electric field on ion crossover in vanadium redox flow batteries

International Nuclear Information System (INIS)

Yang, Xiao-Guang; Ye, Qiang; Cheng, Ping; Zhao, Tim S.

2015-01-01

Highlights: • Effects of the electric field on ion crossover and capacity decay in VRFB are studied. • The model enables the Donnan-potential jumps to be captured at electrode/membrane interfaces. • Electric field arises and affects ion crossover even at the open-circuit condition. • Enhancing electric-field-driven crossover can mitigate the capacity decay rate. - Abstract: A thorough understanding of the mechanisms of ion crossover through the membranes in vanadium redox flow batteries (VRFBs) is critically important in making improvements to the battery’s efficiency and cycling performance. In this work, we develop a 2-D VRFB model to investigate the mechanisms of ion crossover and the associated impacts it has on the battery’s performance. Unlike previously described models in the literature that simulated a single cell by dividing it into the positive electrode, membrane, and negative electrode regions, the present model incorporates all possible ion crossover mechanisms in the entire cell without a need to specify any interfacial boundary conditions at the membrane/electrode interfaces, and hence accurately captures the Donnan-potential jumps and steep gradient of species concentrations at the membrane/electrode interfaces. With our model, a particular emphasis is given to investigation of the effect of the electric field on vanadium ion crossover. One of the significant findings is that an electric field exists in the membrane even under the open-circuit condition, primarily due to the presence of the H + concentration gradient across the membrane. This finding suggests that vanadium ions can permeate through the membrane from H + -diluted to H + -concentrated sides via migration and convection. More importantly, it is found that the rate of vanadium ion crossover and capacity decay during charge and discharge vary with the magnitude of the electric field, which is influenced by the membrane properties and operating conditions. The simulations

Dimensional crossover in fragmentation

Science.gov (United States)

Sotolongo-Costa, Oscar; Rodriguez, Arezky H.; Rodgers, G. J.

2000-11-01

Experiments in which thick clay plates and glass rods are fractured have revealed different behavior of fragment mass distribution function in the small and large fragment regions. In this paper we explain this behavior using non-extensive Tsallis statistics and show how the crossover between the two regions is caused by the change in the fragments’ dimensionality during the fracture process. We obtain a physical criterion for the position of this crossover and an expression for the change in the power-law exponent between the small and large fragment regions. These predictions are in good agreement with the experiments on thick clay plates.

One-Particle vs. Two-Particle Crossover in Weakly Coupled Hubbard Chains and Ladders: Perturbative Renormalization Group Approach

OpenAIRE

Kishine, Jun-ichiro; Yonemitsu, Kenji

1997-01-01

Physical nature of dimensional crossovers in weakly coupled Hubbard chains and ladders has been discussed within the framework of the perturbative renormalization-group approach. The difference between these two cases originates from different universality classes which the corresponding isolated systems belong to.

Resonant two-photon absorption and electromagnetically induced transparency in open ladder-type atomic system.

Science.gov (United States)

Moon, Han Seb; Noh, Heung-Ryoul

2013-03-25

We have experimentally and theoretically studied resonant two-photon absorption (TPA) and electromagnetically induced transparency (EIT) in the open ladder-type atomic system of the 5S(1/2) (F = 1)-5P(3/2) (F' = 0, 1, 2)-5D(5/2) (F″ = 1, 2, 3) transitions in (87)Rb atoms. As the coupling laser intensity was increased, the resonant TPA was transformed to EIT for the 5S(1/2) (F = 1)-5P(3/2) (F' = 2)-5D(5/2) (F″ = 3) transition. The transformation of resonant TPA into EIT was numerically calculated for various coupling laser intensities, considering all the degenerate magnetic sublevels of the 5S(1/2)-5P(3/2)-5D(5/2) transition. From the numerical results, the crossover from TPA to EIT could be understood by the decomposition of the spectrum into an EIT component owing to the pure two-photon coherence and a TPA component caused by the mixed term.

Ringer's lactate, but not hydroxyethyl starch, prolongs the food intolerance time after major abdominal surgery; an open-labelled clinical trial.

Science.gov (United States)

Li, Yuhong; He, Rui; Ying, Xiaojiang; Hahn, Robert G

2015-05-06

The infusion of large amounts of Ringer's lactate prolongs the functional gastrointestinal recovery time and increases the number of complications after open abdominal surgery. We performed an open-labelled clinical trial to determine whether hydroxyethyl starch or Ringer's lactate exerts these adverse effects when the surgery is performed by laparoscopy. Eighty-eight patients scheduled for major abdominal cancer surgery (83% by laparoscopy) received a first-line fluid treatment with 9 ml/kg of either 6% hydroxyethyl starch 130/0.4 (Voluven) or Ringer's lactate, just after induction of anaesthesia; this was followed by a second-line infusion with 12 ml/kg of either starch or Ringer's lactate over 1 hour. Further therapy was managed at the discretion of the attending anaesthetist. Outcome data consisted of postoperative gastrointestinal recovery time, complications and length of hospital stay. The order of the infusions had no impact on the outcome. Both the administration of ≥ 2 L of Ringer's lactate and the development of a surgical complication were associated with a longer time period of paralytic ileus and food intolerance (two-way ANOVA, P food intolerance time amounted to 2 days each. The infusion of ≥ 1 L of hydroxyethyl starch did not adversely affect gastrointestinal recovery. Ringer's lactate, but not hydroxyethyl starch, prolonged the gastrointestinal recovery time in patients undergoing laparoscopic cancer surgery. Surgical complications prolonged the hospital stay.

Extended precedence preservative crossover for job shop scheduling problems

Science.gov (United States)

Ong, Chung Sin; Moin, Noor Hasnah; Omar, Mohd

2013-04-01

Job shop scheduling problems (JSSP) is one of difficult combinatorial scheduling problems. A wide range of genetic algorithms based on the two parents crossover have been applied to solve the problem but multi parents (more than two parents) crossover in solving the JSSP is still lacking. This paper proposes the extended precedence preservative crossover (EPPX) which uses multi parents for recombination in the genetic algorithms. EPPX is a variation of the precedence preservative crossover (PPX) which is one of the crossovers that perform well to find the solutions for the JSSP. EPPX is based on a vector to determine the gene selected in recombination for the next generation. Legalization of children (offspring) can be eliminated due to the JSSP representation encoded by using permutation with repetition that guarantees the feasibility of chromosomes. The simulations are performed on a set of benchmarks from the literatures and the results are compared to ensure the sustainability of multi parents recombination in solving the JSSP.

Two-stage crossover from thermal to quantum flux creep of dilute vortex ensembles in various high-T{sub c} superconducting thin films

Energy Technology Data Exchange (ETDEWEB)

Akerman, Johan J.; Venturini, E. L.; Siegal, M. P.; Yun, S. H.; Karlsson, U. O.; Rao, K. V.

2001-09-01

The thermal-to-quantum flux creep crossover at low vortex densities has been studied in YBa{sub 2}Cu{sub 3}O{sub 7}, TlBa{sub 2}CaCu{sub 2}O{sub 7-{delta}}, and HgBa{sub 2}CaCu{sub 2}O{sub 6+{delta}} thin films using ac susceptibility. The crossover temperatures T{sub cr} are 10--11, 17, and 30 K, respectively. Both thermal and quantum flux creep is suppressed as the vortex density is decreased. We observe a two-stage nature in the crossover behavior which appears to be a general property of all the three materials studied.

Application Period Open for NCI Biospecimen Use | Division of Cancer Prevention

Science.gov (United States)

The application period for investigators interested in obtaining biospecimens and data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial re-opened June 1. A separate application for obtaining biospecimens and data with research funding is also open. |

Experimental investigation of cross-over jets in a rib-roughened trailing-edge cooling channel

Science.gov (United States)

Xue, Fei

Increasing the rotor inlet temperature can dramatically increase the efficiency and power output of the gas turbine engine. However, the melting point of turbine blade material limits the realistic upper bound of the rotor inlet temperature. As a result, the development of high temperature turbine blade material and advanced turbine blade cooling technology determines the future of turbine blade engine. Adding impingement jet holes and rib turbulators in the inner cooling channel of the gas turbine blades are two effective ways to enhance the cooling effects. The purpose of this study is to figure out the influence of different combinations of jet holes and rib turbulators on the heat transfer efficiency. A tabletop scale test model is used in the study to simulate the cooling cavity of trailing edge and its feed channel in a real gas turbine blade. The Dimensional Analysis Theory is used in the study to eliminate the influence of scaling. Two different crossover slots are tested with 5 different rib arrangements, and each of the test geometries is tested for 6 jet Reynolds numbers ranging from 10,000 to 36,000. The two different crossover slots are the crossover slots with 0 and 5 degree tilt angles. The four different rib arrangements are ribs with 0 degree, 45 degree, 90 degree and 135 degree angles of attack with respect to the flow direction. Furthermore, a smooth test section (no ribs) was also tested. The steady state liquid crystal thermography is used to quantify the heat transfer performance of the target areas. The variation of Nusselt number versus Reynolds number is plotted for each of the 10 geometries. Also, the variation of Nusselt number versus Reynolds number are compared for different rib angles of attack with the same crossover slot tilt angle, and between different crossover slots tilt angles with the same rib angle. The results show that, the area-weighted average Nusselt number increases monotonically with the Reynolds number; the target

Randomized open-label trial of dextromethorphan in Rett syndrome.

Science.gov (United States)

Smith-Hicks, Constance L; Gupta, Siddharth; Ewen, Joshua B; Hong, Manisha; Kratz, Lisa; Kelley, Richard; Tierney, Elaine; Vaurio, Rebecca; Bibat, Genila; Sanyal, Abanti; Yenokyan, Gayane; Brereton, Nga; Johnston, Michael V; Naidu, Sakkubai

2017-10-17

To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome. We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist-Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity. Dextromethorphan is safe for use in 3- to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale. Dextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome. This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect. © 2017 American Academy of Neurology.

Role of short periodic orbits in quantum maps with continuous openings

Science.gov (United States)

Prado, Carlos A.; Carlo, Gabriel G.; Benito, R. M.; Borondo, F.

2018-04-01

We apply a recently developed semiclassical theory of short periodic orbits to the continuously open quantum tribaker map. In this paradigmatic system the trajectories are partially bounced back according to continuous reflectivity functions. This is relevant in many situations that include optical microresonators and more complicated boundary conditions. In a perturbative regime, the shortest periodic orbits belonging to the classical repeller of the open map—a cantor set given by a region of exactly zero reflectivity—prove to be extremely robust in supporting a set of long-lived resonances of the continuously open quantum maps. Moreover, for steplike functions a significant reduction in the number needed is obtained, similarly to the completely open situation. This happens despite a strong change in the spectral properties when compared to the discontinuous reflectivity case. In order to give a more realistic interpretation of these results we compare with a Fresnel-type reflectivity function.

Bioequivalence of eslicarbazepine acetate from two different sources of its active product ingredient in healthy subjects.

Science.gov (United States)

Falcão, Amílcar; Lima, Ricardo; Sousa, Rui; Nunes, Teresa; Soares-da-Silva, Patrício

2013-06-01

To compare the bioavailability (BA) and pharmacokinetic (PK) properties and to demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL) in healthy volunteers. Forty healthy male and female subjects aged 18-40 years were randomized to treatment with 400 or 800 mg ESL marketed (MF) formulation [current active pharmaceutical ingredient (API) source] and 400 or 800 mg ESL to-be-marketed (TBM) formulation (new API source) under a gender-balanced, two-period, two-sequence crossover open-label study design. Subjects were assigned to receive either 400 or 800 mg ESL dose strengths, and each was randomly administered on two occasions--either a single oral tablet of MF or a single oral tablet of TBM--separated by a washout period of at least 7 days. Formulations were to be considered bioequivalent if, for both 400 or 800 mg ESL dosage strengths, the test (TBM)/reference (MF) geometric mean ratios (GMR) and 90% confidence intervals (90% CI) of the area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) were within the predetermined range of 80-125%. Test/reference GMR (90% CI) for the Cmax and AUC was respectively 100% (94-109%) and 96% (94-98%) following 400 mg ESL and 100% (95-105%) and 100% (97-103%) following 800 mg ESL. Oral tablet formulations of either 400 or 800 mg ESL from the new API source were found to be bioequivalent to the corresponding marketed Zebinix® formulation according to the regulatory definition of bioequivalence.

Rapid in vitro labeling procedures for two-dimensional gel fingerprinting

International Nuclear Information System (INIS)

Lee, Y.F.; Fowlks, E.R.

1982-01-01

Improvements of existing in vitro procedures for labeling RNA radioactively, and modifications of the two-dimensional polyacrylamide gel electrophoresis system for making RNA fingerprints are described. These improvements are (a) inactivation of phosphatase with nitric acid at pH 2.0 eliminated the phenol-cholorform extraction step during 5'-end labeling with polynucleotide kinase and [γ- 32 P]ATP; (b) ZnSO 4 inactivation of R Nase T 1 results in a highly efficient procedure for 3'-end labeling with T4 ligase and [5'- 32 P]pCp; and (c) a rapid 4-min procedure for variable quantity range of 125 I and RNA results in a qualitative and quantitative sample for high-molecular weight RNA fingerprinting. Thus, these in vitro procedures become rapid and reproducible when combined with two-dimensional gel electrophoresis which eliminates simultaneously labeled impurities. Each labeling procedure is compared, using tobacco mosaic virus, Brome mosaic virus, and polio RNA. A series of Ap-rich oligonucleotides was discovered in the inner genome of Brome mosaic Virus RNA-3

Extra virgin olive oil phenols and markers of oxidation in Greek smokers: a randomized cross-over study

NARCIS (Netherlands)

Moschandreas, J.; Vissers, M.N.; Wiseman, S.; Putte, van K.P.; Kafatos, A.

2002-01-01

Objective: To examine the effect of a low phenol olive oil and high phenol olive oil on markers of oxidation and plasma susceptibility to oxidation in normolipaemic smokers. Design: Randomized single-blind cross-over trial with two intervention periods. Setting: The Medical School and University

Polaron crossover in molecular solids

International Nuclear Information System (INIS)

Zoli, Marco; Das, A N

2004-01-01

An analytical variational method is applied to the molecular Holstein Hamiltonian in which the dispersive features of the dimension dependent phonon spectrum are taken into account by a force constant approach. The crossover between a large and a small size polaron is monitored, in one, two and three dimensions and for different values of the adiabatic parameter, through the behaviour of the effective mass as a function of the electron-phonon coupling. By increasing the strength of the intermolecular forces the crossover becomes smoother and occurs at higher e-ph couplings. These effects are more evident in three dimensions. We show that our modified Lang-Firsov method starts to capture the occurrence of a polaron self-trapping transition when the electron energies become of order of the phonon energies. The self-trapping event persists in the fully adiabatic regime. At the crossover we estimate polaron effective masses of order ∼ 5-40 times the bare band mass according to the dimensionality and the value of the adiabatic parameter. Modified Lang-Firsov polaron masses are substantially reduced in two and three dimensions. There is no self-trapping in the antiadiabatic regime

The effectiveness of healthy meals at work on reaction time, mood and dietary intake: a randomised cross-over study in daytime and shift workers at an university hospital

DEFF Research Database (Denmark)

Leedo, Eva; Beck, Anne Marie; Astrup, Arne

2017-01-01

Our dietary habits affect both cognitive performance and mood. The aim of the study was to examine the effect of increased availability of healthy meals and water at work on healthcare staff. The study used an 8-week randomised cross-over design. A total of sixty physicians, nurses and nursing...... assistants, including sixteen working on shifts, were recruited. The participants received a self-selected keyhole-labelled (Nordic nutrition label) lunch, snack and bottled water during each shift throughout the intervention period. Reaction time (Go/No-Go test), mood-related scores (POMS) and dietary....... The intervention had no effect on reaction time or any of the mood-related scores in the group as a whole. In shift-working participants, the intervention period resulted in a 31·1 % lower Fatigue-Inertia Score (P=0·003), a 15·3 % higher Vigour-Activity Score (P=0·041) and a 42·7 % lower Total Mood Disturbance...

Radiosynthesis and evaluation of two novel 123I-labeled 2-methyl-4-nitroimidazole derivatives as potential infection imaging agents.

Science.gov (United States)

Rossouw, Daniel D; Lötter, Mattheus G; du Raan, Hanlie; Jansen, Susara E; Höhn, Alexander; Burger, Ben V

2005-05-01

The inflammation- and infection-seeking properties of (131)I-labeled ornidazole, a 5-nitroimidazole derivative, have recently been reported. Whole-body images in rabbits showed a more rapid uptake in inflamed areas compared to (67)Ga. In the present study, two novel (123)I-labeled 2-methyl-4-nitroimidazole derivatives were synthesized and their infection-seeking properties compared with those of (67)Ga and (123)I-labeled ornidazole. Radiolabeling was carried out by means of iodide-for-tosylate, triflate or halogen exchange. Various methods were utilized in order to synthesize the labeling precursors for the (123)I-labeled novel compounds. Serum stability studies on all of the (123)I-labeled tracers were followed by gamma camera imaging studies on rabbits artificially infected with Escherichia coli bacteria. The (123)I-labeled tracers were obtained in moderate to good radiochemical yields (34-80%) and acceptable radiochemical purities (93-99%). In contrast to (123)I-labeled ornidazole, 1-[(1-hydroxy-3-[(123)I]iodoprop-2-yloxy)methyl]-2-methyl-4-nitroimidazole (2) and 1-[(1-[(123)I]iodoprop-2-yloxy)methyl]-2-methyl-4-nitroimidazole (3) showed high serum stability. Compared to noninfected controls, all of the (123)I-labeled tracers showed increased uptake at the area of induced infection after 6 and 24 h, but the uptake was significantly lower than in the case of (67)Ga over the same period. Tracer 3 showed a slightly superior uptake after 6 h than the other (123)I-labeled tracers over the same period. The advantage of the initially slightly faster rate at which nitroimidazole tracers appear to accumulate in the infection area in comparison to (67)Ga might not outweigh the advantage of the eventual higher target to nontarget ratio displayed by (67)Ga.

Frequency-Modulated Wave Dielectrophoresis of Vesicles And Cells: Periodic U-Turns at the Crossover Frequency

Science.gov (United States)

Frusawa, Hiroshi

2018-06-01

We have formulated the dielectrophoretic force exerted on micro/nanoparticles upon the application of frequency-modulated (FM) electric fields. By adjusting the frequency range of an FM wave to cover the crossover frequency f X in the real part of the Clausius-Mossotti factor, our theory predicts the reversal of the dielectrophoretic force each time the instantaneous frequency periodically traverses f X . In fact, we observed periodic U-turns of vesicles, leukemia cells, and red blood cells that undergo FM wave dielectrophoresis (FM-DEP). It is also suggested by our theory that the video tracking of the U-turns due to FM-DEP is available for the agile and accurate measurement of f X . The FM-DEP method requires a short duration, less than 30 s, while applying the FM wave to observe several U-turns, and the agility in measuring f X is of much use for not only salty cell suspensions but also nanoparticles because the electric-field-induced solvent flow is suppressed as much as possible. The accuracy of f X has been verified using two types of experiment. First, we measured the attractive force exerted on a single vesicle experiencing alternating-current dielectrophoresis (AC-DEP) at various frequencies of sinusoidal electric fields. The frequency dependence of the dielectrophoretic force yields f X as a characteristic frequency at which the force vanishes. Comparing the AC-DEP result of f X with that obtained from the FM-DEP method, both results of f X were found to coincide with each other. Second, we investigated the conductivity dependencies of f X for three kinds of cell by changing the surrounding electrolytes. From the experimental results, we evaluated simultaneously both of the cytoplasmic conductivities and the membrane capacitances using an elaborate theory on the single-shell model of biological cells. While the cytoplasmic conductivities, similar for these cells, were slightly lower than the range of previous reports, the membrane capacitances obtained

Relativistic BCS-BEC Crossover at Quark Level

Directory of Open Access Journals (Sweden)

Zhuang P.

2010-10-01

Full Text Available The non-relativistic G0G formalism of BCS-BEC crossover at finite temperature is extended to relativistic fermion systems. The theory recovers the BCS mean field approximation at zero temperature and the non-relativistic results in a proper limit. For massive fermions, when the coupling strength increases, there exist two crossovers from the weak coupling BCS superfluid to the non-relativistic BEC state and then to the relativistic BEC state. For color superconductivity at moderate baryon density, the matter is in the BCS-BEC crossover region, and the behavior of the pseudogap is quite similar to that found in high temperature superconductors.

An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia

Directory of Open Access Journals (Sweden)

Pandina Gahan

2012-06-01

Full Text Available Abstract Background Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. Methods This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children’s Global Assessment Scale, adverse event (AE monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. Results A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7% subjects completed this study: 209 of the 279 subjects (75% in the 6-month group and 55 of the 111 subjects (50% in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (≥10% of subjects were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs were reported by 36 (9% subjects. The AE profile in this study was

Extra virgin olive oil phenols and markers of oxidation in Greek smokers: a randomized cross-over study.

Science.gov (United States)

Moschandreas, J; Vissers, M N; Wiseman, S; van Putte, K P; Kafatos, A

2002-10-01

To examine the effect of a low phenol olive oil and high phenol olive oil on markers of oxidation and plasma susceptibility to oxidation in normolipaemic smokers. Randomized single-blind cross-over trial with two intervention periods. The Medical School and University Hospital of the University of Crete, Heraklion, Crete, Greece. Twenty-five healthy males and females completed the study. Each intervention was of three weeks duration and intervention periods were separated by a two week washout. Seventy grams of extra virgin olive oil was supplied to each subject per day in the intervention periods. The olive oils supplied differed in their phenol content by 18.6 mg/day. Two fasting venous blood samples were taken at the end of each intervention period. The markers of antioxidant capacity measured in fasting plasma samples (total plasma resistance to oxidation, concentrations of protein carbonyl as a marker of protein oxidation, malondialdehyde and lipid hydroperoxides as markers of lipid oxidation and the ferric reducing ability of plasma) did not differ significantly between the low and high phenol olive oil diets. No effect of olive oil phenols on markers of oxidation in smokers was detected. It may be that the natural concentrations of phenols in olive oil are too low to produce an effect in the post-absorptive phase. Possible reasons for period effects and interactions between diet and administration period need attention to aid further cross-over trials of this kind. Unilever Research Vlaardingen, The Netherlands.

A randomized, 2-period, crossover design study to assess the effects of dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers.

Science.gov (United States)

Frelinger, Andrew L; Lee, Ronald D; Mulford, Darcy J; Wu, Jingtao; Nudurupati, Sai; Nigam, Anu; Brooks, Julie K; Bhatt, Deepak L; Michelson, Alan D

2012-04-03

The aim of this study was to assess the effects of different proton pump inhibitors (PPIs) on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel. Metabolism of clopidogrel requires cytochrome P450s (CYPs), including CYP2C19. However, PPIs may inhibit CYP2C19, potentially reducing the effectiveness of clopidogrel. A randomized, open-label, 2-period, crossover study of healthy subjects (n = 160, age 18 to 55 years, homozygous for CYP2C19 extensive metabolizer genotype, confined, standardized diet) was conducted. Clopidogrel 75 mg with or without a PPI (dexlansoprazole 60 mg, lansoprazole 30 mg, esomeprazole 40 mg, or, as a positive control to maximize potential interaction and demonstrate assay sensitivity, omeprazole 80 mg) was given daily for 9 days. Pharmacokinetics and pharmacodynamics were assessed on days 9 and 10. Pharmacodynamic end-points were vasodilator-stimulated phosphoprotein P2Y(12) platelet reactivity index, maximal platelet aggregation to 5 and 20 μmol/l adenosine diphosphate, and VerifyNow P2Y12 platelet response units. Pharmacokinetic and pharmacodynamic responses with omeprazole demonstrated assay sensitivity. The area under the curve for clopidogrel active metabolite decreased significantly with esomeprazole but not with dexlansoprazole or lansoprazole. Similarly, esomeprazole but not dexlansoprazole or lansoprazole significantly reduced the effect of clopidogrel on vasodilator-stimulated phosphoprotein platelet reactivity index. All PPIs decreased the peak plasma concentration of clopidogrel active metabolite (omeprazole > esomeprazole > lansoprazole > dexlansoprazole) and showed a corresponding order of potency for effects on maximal platelet aggregation and platelet response units. Generation of clopidogrel active metabolite and inhibition of platelet function were reduced less by the coadministration of dexlansoprazole or lansoprazole with clopidogrel than by the coadministration of esomeprazole or omeprazole. These

Minocycline treatment in acute stroke: an open-label, evaluator-blinded study.

Science.gov (United States)

Lampl, Y; Boaz, M; Gilad, R; Lorberboym, M; Dabby, R; Rapoport, A; Anca-Hershkowitz, M; Sadeh, M

2007-10-02

Ischemic animal model studies have shown a neuroprotective effect of minocycline. To analyze the effect of minocycline treatment in human acute ischemic stroke. We performed an open-label, evaluator-blinded study. Minocycline at a dosage of 200 mg was administered orally for 5 days. The therapeutic window of time was 6 to 24 hours after onset of stroke. Data from NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) were evaluated. The primary objective was to compare changes from baseline to day 90 in NIHSS in the minocycline group vs placebo. One hundred fifty-two patients were included in the study. Seventy-four patients received minocycline treatment, and 77 received placebo. NIHSS and mRS were significantly lower and BI scores were significantly higher in minocycline-treated patients. This pattern was already apparent on day 7 and day 30 of follow-up. Deaths, myocardial infarctions, recurrent strokes, and hemorrhagic transformations during follow-up did not differ by treatment group. Patients with acute stroke had significantly better outcome with minocycline treatment compared with placebo. The findings suggest a potential benefit of minocycline in acute ischemic stroke.

A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study).

Science.gov (United States)

Starling, Amaal J; Tepper, Stewart J; Marmura, Michael J; Shamim, Ejaz A; Robbins, Matthew S; Hindiyeh, Nada; Charles, Andrew C; Goadsby, Peter J; Lipton, Richard B; Silberstein, Stephen D; Gelfand, Amy A; Chiacchierini, Richard P; Dodick, David W

2018-05-01

Objective To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine. Background sTMS was originally developed for the acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention. Methods The eNeura SpringTMS Post-Market Observational U.S. Study of Migraine (ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity. Results Of a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a -2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (-0.63 days) ( p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher ( p < 0.0001) than the performance goal (20%). There was a reduction of -2

Modelling of the PROTO-II crossover network

International Nuclear Information System (INIS)

Proulx, G.A.; Lackner, H.; Spence, P.; Wright, T.P.

1985-01-01

In order to drive a double ring, symmetrically fed bremsstrahlung diode, the PROTO II accelerator was redesigned. The radially converging triplate water line was reconfigured to drive two radial converging triplate lines in parallel. The four output lines were connected to the two input lines via an electrically enclosed tubular crossover network. Low-voltage Time Domain Reflectrometry (TDR) experiments were conducted on a full scale water immersed model of one section of the crossover network as an aid in this design. A lumped element analysis of the power flow through the network was inadequate in explaining the observed wave transmission and reflection characteristics. A more detailed analysis was performed with a circuit code in which we considered both localized lump-element and transmission line features of the crossover network. Experimental results of the model tests are given and compared with the circuit simulations. 7 figs

The Effects of Individual Upper Alpha Neurofeedback in ADHD: An Open-Label Pilot Study

OpenAIRE

Escolano , Carlos; Navarro-Gil , Mayte; Garcia-Campayo , Javier; Congedo , Marco; Minguez , Javier

2014-01-01

International audience; Standardized neurofeedback (NF) protocols have been extensively evaluated in attention-deficit/hyperactivity disorder (ADHD). However, such protocols do not account for the large EEG heterogeneity in ADHD. Thus, individualized approaches have been suggested to improve the clinical outcome. In this direction, an open-label pilot study was designed to evaluate a NF protocol of relative upper alpha power enhancement in fronto-central sites. Upper alpha band was individual...

The melting and abundance of open charm hadrons

Directory of Open Access Journals (Sweden)

A. Bazavov

2014-10-01

Full Text Available Ratios of cumulants of conserved net charge fluctuations are sensitive to the degrees of freedom that are carriers of the corresponding quantum numbers in different phases of strong interaction matter. Using lattice QCD with 2+1 dynamical flavors and quenched charm quarks we calculate second and fourth order cumulants of net charm fluctuations and their correlations with other conserved charges such as net baryon number, electric charge and strangeness. Analyzing appropriate ratios of these cumulants we probe the nature of charmed degrees of freedom in the vicinity of the QCD chiral crossover region. We show that for temperatures above the chiral crossover transition temperature, charmed degrees of freedom can no longer be described by an uncorrelated gas of hadrons. This suggests that the dissociation of open charm hadrons and the emergence of deconfined charm states sets in just near the chiral crossover transition. Till the crossover region we compare these lattice QCD results with two hadron resonance gas models—including only the experimentally established charmed resonances and also including additional states predicted by quark model and lattice QCD calculations. This comparison provides evidence for so far unobserved charmed hadrons that contribute to the thermodynamics in the crossover region.

Comparison of Two Kinds of 64Cu Labelled Octreotide Analogues

Directory of Open Access Journals (Sweden)

HAN Zhen-yi1;LIANG Ji-xin1;HU Ji2;LUO Hong-yi1;QING Jing2;CHEN Yu-qing2;LI Guang2;LI Hong-yu1,2

2016-10-01

Full Text Available Octreotide analogues DOTA-TOC and DOTA-TATE were labeled with 64Cu. The influences of the ratio of peptide mass to 64Cu activity, pH value, temperature and reaction time on labeling yield were investigated. The optimum labeling was determined. In vitro stability tests in saline and 10% bovine serum had been carried out. Biodistribution of the two radiolabelled compounds in normal mice and Micro PET imaging in nude mice bearing U87MG tumor had been evaluated. The results showed that the labeling yields of 64Cu-DOTA-TOC and 64Cu-DOTA-TATE were higher than 95%. Two kinds of octreotide analogues labeled with 64Cu were quite stable in saline and decomposed slowly in 10% bovine serum at 37 ℃. Biodistribution results in normal mice showed that two 64Cu labelled tracers had similar profiles. Both of the compounds washed out from the blood quickly. High uptake of radioactivity in liver and kidneys indicated the tracers were excreted via both hepatobiliary system and renal system. At the same time, compared to 64Cu-DOTA-TOC, higher radioactivity accumulation of 64Cu-DOTA-TATE in liver and kidneys was observed. Micro PET images of U87MG tumor-bearing nude mice with 64Cu-DOTA-TOC and 64Cu-DOTA-TATE showed the tumors very clearly. The radioactivity uptake of 64Cu-DOTA-TATE in tumor was higher than that of 64Cu-DOTA-TOC. This work has paved the way for further preclinical and clinical application of 64Cu-DOTA-TOC and 64Cu-DOTA-TATE as PET tumor imaging agents.

The crossover from collective motion to periphery diffusion for two-dimensional adatom-islands on Cu(111)

International Nuclear Information System (INIS)

Karim, Altaf; Kara, Abdelkader; Rahman, Talat S; Trushin, Oleg

2011-01-01

The diffusion of two-dimensional adatom-islands (up to 100 atoms) on Cu(111) has been studied, using the self-learning kinetic Monte Carlo method (Trushin et al 2005 Phys. Rev. B 72 115401). A variety of multiple- and single-atom processes are revealed in the simulations, and the size dependences of the diffusion coefficients and effective diffusion barriers are calculated for each. From the tabulated frequencies of events found in the simulation, we show a crossover from diffusion due to the collective motion of the island to a regime in which the island diffuses through periphery-dominated mass transport. This crossover occurs for island sizes between 13 and 19 atoms. For islands containing 19-100 atoms the scaling exponent is 1.5, which is in good agreement with previous work. The diffusion of islands containing 2-13 atoms can be explained primarily on the basis of a linear increase of the barrier for the collective motion with the size of the island. (fast track communication)

Canonical Labelling of Site Graphs

Directory of Open Access Journals (Sweden)

Nicolas Oury

2013-06-01

Full Text Available We investigate algorithms for canonical labelling of site graphs, i.e. graphs in which edges bind vertices on sites with locally unique names. We first show that the problem of canonical labelling of site graphs reduces to the problem of canonical labelling of graphs with edge colourings. We then present two canonical labelling algorithms based on edge enumeration, and a third based on an extension of Hopcroft's partition refinement algorithm. All run in quadratic worst case time individually. However, one of the edge enumeration algorithms runs in sub-quadratic time for graphs with "many" automorphisms, and the partition refinement algorithm runs in sub-quadratic time for graphs with "few" bisimulation equivalences. This suite of algorithms was chosen based on the expectation that graphs fall in one of those two categories. If that is the case, a combined algorithm runs in sub-quadratic worst case time. Whether this expectation is reasonable remains an interesting open problem.

Understanding the cluster randomised crossover design: a graphical illustraton of the components of variation and a sample size tutorial.

Science.gov (United States)

Arnup, Sarah J; McKenzie, Joanne E; Hemming, Karla; Pilcher, David; Forbes, Andrew B

2017-08-15

In a cluster randomised crossover (CRXO) design, a sequence of interventions is assigned to a group, or 'cluster' of individuals. Each cluster receives each intervention in a separate period of time, forming 'cluster-periods'. Sample size calculations for CRXO trials need to account for both the cluster randomisation and crossover aspects of the design. Formulae are available for the two-period, two-intervention, cross-sectional CRXO design, however implementation of these formulae is known to be suboptimal. The aims of this tutorial are to illustrate the intuition behind the design; and provide guidance on performing sample size calculations. Graphical illustrations are used to describe the effect of the cluster randomisation and crossover aspects of the design on the correlation between individual responses in a CRXO trial. Sample size calculations for binary and continuous outcomes are illustrated using parameters estimated from the Australia and New Zealand Intensive Care Society - Adult Patient Database (ANZICS-APD) for patient mortality and length(s) of stay (LOS). The similarity between individual responses in a CRXO trial can be understood in terms of three components of variation: variation in cluster mean response; variation in the cluster-period mean response; and variation between individual responses within a cluster-period; or equivalently in terms of the correlation between individual responses in the same cluster-period (within-cluster within-period correlation, WPC), and between individual responses in the same cluster, but in different periods (within-cluster between-period correlation, BPC). The BPC lies between zero and the WPC. When the WPC and BPC are equal the precision gained by crossover aspect of the CRXO design equals the precision lost by cluster randomisation. When the BPC is zero there is no advantage in a CRXO over a parallel-group cluster randomised trial. Sample size calculations illustrate that small changes in the specification of

Armodafinil for fatigue associated with menopause: an open-label trial.

Science.gov (United States)

Meyer, Fremonta; Freeman, Marlene P; Petrillo, Laura; Barsky, Maria; Galvan, Thania; Kim, Semmie; Cohen, Lee; Joffe, Hadine

2016-02-01

This study aims to obtain preliminary data on the efficacy of armodafinil for improving menopause-related fatigue and quality of life. Women (aged 40-65 y) experiencing menopause-related fatigue received open-label armodafinil therapy (up to 150 mg/d) for 4 weeks. Changes from baseline in Brief Fatigue Inventory score and Menopause-Specific Quality of Life (MENQOL) physical domain score were examined using the Wilcoxon signed rank test. Exploratory analyses examined the effects of armodafinil on hot flashes, overall quality of life, insomnia, depression, anxiety, and perceived cognitive performance. After open-label treatment, participants were randomized to double-blind continuation of armodafinil versus placebo for 2 weeks to examine whether treatment discontinuation would precipitate symptom recurrence. Of 29 eligible participants, 20 women (69.0%) completed the trial. During treatment with armodafinil (mean dose, 120 mg/d), median Brief Fatigue Inventory scores decreased by 57.7% from 5.2 (interquartile range [IQR], 4.6-6.2) to 2.2 (IQR, 1.1-4.4; P = 0.0002), and median MENQOL physical domain scores decreased by 51.3% from 3.9 (IQR, 2.3-4.8) to 1.9 (IQR, 1.3-2.7; P = 0.0001). Median hot flashes for 24 hours decreased by 48.3% from 2.9 (IQR, 1.1-4.6) to 1.5 (IQR, 0.4-2.4; P = 0.0005). Improvements in MENQOL total score (49%; P = 0.0001), cognitive function (59.2%; P = 0.0002), depressive symptoms (64.7%; P = 0.0006), insomnia (72.7%; P = 0.0012), and excessive sleepiness (57.1%; P = 0.0006) were noted. Randomized continuation (n = 10) or discontinuation (n = 10) did not indicate group differences. Armodafinil was well-tolerated; three women (12%) were withdrawn for adverse events. These preliminary results suggest a therapeutic effect of armodafinil on fatigue affecting quality of life during menopause, and a potential benefit for other menopause-related symptoms.

Effect of varying the exposure and 3H-thymidine labeling period upon the outcome of the primary hepatocyte DNA repair assay

International Nuclear Information System (INIS)

Barfknecht, T.R.; Mecca, D.J.; Naismith, R.W.

1988-01-01

The results presented in this report demonstrate that an 18-20 hour exposure/ 3 H-thymidine DNA labeling period is superior to a 4 hour incubation interval for general genotoxicity screening studies in the rat primary hepatocyte DNA repair assay. When DNA damaging agents which give rise to bulky-type DNA base adducts such as 2-acetylaminofluorene, aflatoxin B1 and benzidine were evaluated, little or no difference was observed between the 4 hour or an 18-20-hour exposure/labeling period. Similar results were also noted for the DNA ethylating agent diethylnitrosamine. However, when DNA damaging chemicals which produce a broader spectrum of DNA lesions were studied, differences in the amount of DNA repair as determined by autoradiographic analysis did occur. Methyl methanesulfonate and dimethylnitrosamine induced repairable DNA damage that was detected at lower dose levels with the 18-20 hour exposure/labeling period. Similar results were also observed for the DNA cross-linking agents, mitomycin C and nitrogen mustard. Ethyl methanesulfonate produced only a marginal amount of DNA repair in primary hepatocytes up to a dose level of 10(-3) M during the 4 hour incubation period, whereas a substantial amount of DNA repair was detectable at a dose level of 2.5 X 10(-4) M when the 18-20 hour exposure/labeling period was employed. The DNA alkylating agent 4-nitroquinoline-1-oxide, which creates DNA base adducts that are slowly removed from mammalian cell DNA, induced no detectable DNA repair in hepatocytes up to a toxic dose level of 2 X 10(-5) M with the 4 hour exposure period, whereas a marked DNA repair response was observed at 10(-5) M when the 18-20 hour exposure/labeling period was used

Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study

Directory of Open Access Journals (Sweden)

Caio Abujadi

2017-12-01

Full Text Available Objective: Theta-burst stimulation (TBS modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD. At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Methods: Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Results: Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. Conclusion: These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study.

Science.gov (United States)

Abujadi, Caio; Croarkin, Paul E; Bellini, Bianca B; Brentani, Helena; Marcolin, Marco A

2017-12-11

Theta-burst stimulation (TBS) modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD). At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS) to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

Catalytic Activity Control via Crossover between Two Different Microstructures

KAUST Repository

Zhou, Yuheng

2017-09-08

Metal nanocatalysts hold great promise for a wide range of heterogeneous catalytic reactions, while the optimization strategy of catalytic activity is largely restricted by particle size or shape control. Here, we demonstrate that a reversible microstructural control through the crossover between multiply-twinned nanoparticle (MTP) and single crystal (SC) can be readily achieved by solvent post-treatment on gold nanoparticles (AuNPs). Polar solvents (e.g. water, methanol) direct the transformation from MTP to SC accompanied by the disappearance of twinning and stacking faults. A reverse transformation from SC to MTP is achieved in non-polar solvent (e.g. toluene) mixed with thiol ligands. The transformation between two different microstructures is directly observed by in-situ TEM and leads to a drastic modulation of catalytic activity towards the gas-phase selective oxidation of alcohols. There is a quasi-linear relationship between TOFs and MTP concentrations. Based on the combined experimental and theoretical investigations of alcohol chemisorption on these nanocatalysts, we propose that the exposure of {211}-like microfacets associated with twin boundaries and stack faults accounts for the strong chemisorption of alcohol molecules on MTP AuNPs and thus the exceptionally high catalytic activity.

An Open-Source Label Atlas Correction Tool and Preliminary Results on Huntingtons Disease Whole-Brain MRI Atlases.

Science.gov (United States)

Forbes, Jessica L; Kim, Regina E Y; Paulsen, Jane S; Johnson, Hans J

2016-01-01

The creation of high-quality medical imaging reference atlas datasets with consistent dense anatomical region labels is a challenging task. Reference atlases have many uses in medical image applications and are essential components of atlas-based segmentation tools commonly used for producing personalized anatomical measurements for individual subjects. The process of manual identification of anatomical regions by experts is regarded as a so-called gold standard; however, it is usually impractical because of the labor-intensive costs. Further, as the number of regions of interest increases, these manually created atlases often contain many small inconsistently labeled or disconnected regions that need to be identified and corrected. This project proposes an efficient process to drastically reduce the time necessary for manual revision in order to improve atlas label quality. We introduce the LabelAtlasEditor tool, a SimpleITK-based open-source label atlas correction tool distributed within the image visualization software 3D Slicer. LabelAtlasEditor incorporates several 3D Slicer widgets into one consistent interface and provides label-specific correction tools, allowing for rapid identification, navigation, and modification of the small, disconnected erroneous labels within an atlas. The technical details for the implementation and performance of LabelAtlasEditor are demonstrated using an application of improving a set of 20 Huntingtons Disease-specific multi-modal brain atlases. Additionally, we present the advantages and limitations of automatic atlas correction. After the correction of atlas inconsistencies and small, disconnected regions, the number of unidentified voxels for each dataset was reduced on average by 68.48%.

Efficacy and safety of saxagliptin in combination with insulin in Japanese patients with type 2 diabetes mellitus: a 16-week double-blind randomized controlled trial with a 36-week open-label extension.

Science.gov (United States)

Kadowaki, Takashi; Muto, Satsuki; Ouchi, Yoshiumi; Shimazaki, Ryutaro; Seino, Yutaka

2017-12-01

We examined the efficacy and safety of saxagliptin as an add-on to insulin in Japanese patients with type 2 diabetes mellitus. We randomized 240 patients with type 2 diabetes mellitus on insulin monotherapy to 5-mg saxagliptin or placebo as add-on therapy for a 16-week, double-blind period. All patients received 5-mg saxagliptin and insulin for an additional 36 weeks (open-label extension). Change in hemoglobin A1c (HbA1c) at Week 16 was the main endpoint. At Week 16, the adjusted change in HbA1c from baseline increased by 0.51% with placebo and decreased by 0.40% with saxagliptin (difference -0.92% [95% confidence interval -1.07%, -0.76%; p 1]). In patients receiving saxagliptin, reductions in HbA1c at Week 16 were maintained to Week 52, while switching from placebo to saxagliptin resulted in a similar reduction in HbA1c. The incidence of hypoglycemia was not markedly increased with saxagliptin versus placebo in the double-blind period and did not increase substantially during the open-label extension period. The efficacy and safety of saxagliptin was similar between the elderly and non-elderly patient groups. Adding saxagliptin to ongoing insulin therapy improved glycemic control and was well tolerated in Japanese patients with type 2 diabetes.

Linear combinations come alive in crossover designs.

Science.gov (United States)

Shuster, Jonathan J

2017-10-30

Before learning anything about statistical inference in beginning service courses in biostatistics, students learn how to calculate the mean and variance of linear combinations of random variables. Practical precalculus examples of the importance of these exercises can be helpful for instructors, the target audience of this paper. We shall present applications to the "1-sample" and "2-sample" methods for randomized short-term 2-treatment crossover studies, where patients experience both treatments in random order with a "washout" between the active treatment periods. First, we show that the 2-sample method is preferred as it eliminates "conditional bias" when sample sizes by order differ and produces a smaller variance. We also demonstrate that it is usually advisable to use the differences in posttests (ignoring baseline and post washout values) rather than the differences between the changes in treatment from the start of the period to the end of the period ("delta of delta"). Although the intent is not to provide a definitive discussion of crossover designs, we provide a section and references to excellent alternative methods, where instructors can provide motivation to students to explore the topic in greater detail in future readings or courses. Copyright © 2017 John Wiley & Sons, Ltd.

Hybrid Genetic Algorithm with Multiparents Crossover for Job Shop Scheduling Problems

Directory of Open Access Journals (Sweden)

Noor Hasnah Moin

2015-01-01

Full Text Available The job shop scheduling problem (JSSP is one of the well-known hard combinatorial scheduling problems. This paper proposes a hybrid genetic algorithm with multiparents crossover for JSSP. The multiparents crossover operator known as extended precedence preservative crossover (EPPX is able to recombine more than two parents to generate a single new offspring distinguished from common crossover operators that recombine only two parents. This algorithm also embeds a schedule generation procedure to generate full-active schedule that satisfies precedence constraints in order to reduce the search space. Once a schedule is obtained, a neighborhood search is applied to exploit the search space for better solutions and to enhance the GA. This hybrid genetic algorithm is simulated on a set of benchmarks from the literatures and the results are compared with other approaches to ensure the sustainability of this algorithm in solving JSSP. The results suggest that the implementation of multiparents crossover produces competitive results.

Open-label placebo treatment in chronic low back pain: a randomized controlled trial.

Science.gov (United States)

Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J; Kirsch, Irving

2016-12-01

This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland-Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (-0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain.

Role of open boundary conditions on the hysteretic behaviour of one-dimensional spin crossover nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Chiruta, Daniel [GEMaC, Université de Versailles Saint-Quentin-en-Yvelines, CNRS-UVSQ (UMR 8635), 78035 Versailles Cedex (France); Faculty of Electrical Engineering and Computer Science, Stefan cel Mare University, Suceava 720229 (Romania); Linares, Jorge, E-mail: jorge.linares@uvsq.fr, E-mail: miya@spin.phys.s.u-tokyo.ac.jp; Boukheddaden, Kamel [GEMaC, Université de Versailles Saint-Quentin-en-Yvelines, CNRS-UVSQ (UMR 8635), 78035 Versailles Cedex (France); Miyashita, Seiji, E-mail: jorge.linares@uvsq.fr, E-mail: miya@spin.phys.s.u-tokyo.ac.jp [Department of Physics, Graduate School of Science, University of Tokyo, Bunkyo-Ku, Tokyo (Japan); CREST, JST, 4-1-8 Honcho Kawaguchi, Saitama 332-0012 (Japan)

2014-05-21

In order to explain clearly the role of the open boundary conditions (OBCs) on phase transition in one dimensional system, we consider an Ising model with both short-range (J) and long-range (G) interactions, which has allowed us to study the cooperative nature of spin-crossover (SCO) materials at the nanometer scale. At this end, we developed a transfer-matrix method for one-dimensional (1D) SCO system with free boundary conditions, and we give numerical evidences for how the thermal spin transition curves vary as a function of the physical parameters (J, G) or an applied pressure. Moreover for OBCs case, we have derived the bulk, surface and finite-size contributions to the free energy and we have investigated the variation of these energies as function of J and system size. We have found that the surface free energy behaves like J〈σ〉{sup 2}, where 〈σ〉 is the average magnetization per site. Since the properties of the nanometric scale are dramatically influenced by the system's size (N), our analytical outcomes for the size dependence represent a step to achieve new characteristic of the future devices and also a way to find various novel properties which are absent in the bulk materials.

DMFC performance and methanol cross-over: Experimental analysis and model validation

Energy Technology Data Exchange (ETDEWEB)

Casalegno, A.; Marchesi, R. [Dipartimento di Energia, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

2008-10-15

A combined experimental and modelling approach is proposed to analyze methanol cross-over and its effect on DMFC performance. The experimental analysis is performed in order to allow an accurate investigation of methanol cross-over influence on DMFC performance, hence measurements were characterized in terms of uncertainty and reproducibility. The findings suggest that methanol cross-over is mainly determined by diffusion transport and affects cell performance partly via methanol electro-oxidation at the cathode. The modelling analysis is carried out to further investigate methanol cross-over phenomenon. A simple model evaluates the effectiveness of two proposed interpretations regarding methanol cross-over and its effects. The model is validated using the experimental data gathered. Both the experimental analysis and the proposed and validated model allow a substantial step forward in the understanding of the main phenomena associated with methanol cross-over. The findings confirm the possibility to reduce methanol cross-over by optimizing anode feeding. (author)

Short-term effects of crossover treatment with silodosin and tamsulosin hydrochloride for lower urinary tract symptoms associated with benign prostatic hyperplasia.

Science.gov (United States)

Miyakita, Hideshi; Yokoyama, Eiji; Onodera, Yasutada; Utsunomiya, Takuji; Tokunaga, Masatoshi; Tojo, Takanori; Fujii, Noriteru; Yanada, Shuichi

2010-10-01

To compare the efficacy and safety of silodosin and tamsulosin in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) by a randomized crossover method. BPH patients with the complaint of LUTS were included in this study, and were randomly divided into two groups: a silodosin-preceding group (4 weeks of twice-daily administration of silodosin at 4 mg, followed by 4 weeks of once-daily administration of tamsulosin at 0.2 mg) or a tamsulosin-preceding group (4 weeks' administration of tamsulosin, followed by 4 weeks' administration of silodosin). No drug withdrawal period was provided when switching the drug. In the first treatment period, both drugs significantly improved the International Prostate Symptom Score total score, but the improvement by silodosin was significantly superior to that by tamsulosin. After crossover treatment, significant improvement was observed only with silodosin treatment. Moreover, intergroup comparison of changes revealed that silodosin showed significant improvement of straining and nocturia with first and crossover treatments, respectively, compared with tamsulosin. Silodosin also significantly improved quality of life (QOL) score in both treatment periods, while tamsulosin significantly improved QOL score only in the first treatment period. The most frequent adverse drug reaction was ejaculatory disorder with silodosin; however, the incidence of dizziness with silodosin was similar to that with tamsulosin. In BPH/LUTS patients, silodosin exhibits excellent efficacy in improving subjective symptoms in both initial and crossover treatment, and it appears to improve the QOL of patients. © 2010 The Japanese Urological Association.

Crossover ensembles of random matrices and skew-orthogonal polynomials

International Nuclear Information System (INIS)

Kumar, Santosh; Pandey, Akhilesh

2011-01-01

Highlights: → We study crossover ensembles of Jacobi family of random matrices. → We consider correlations for orthogonal-unitary and symplectic-unitary crossovers. → We use the method of skew-orthogonal polynomials and quaternion determinants. → We prove universality of spectral correlations in crossover ensembles. → We discuss applications to quantum conductance and communication theory problems. - Abstract: In a recent paper (S. Kumar, A. Pandey, Phys. Rev. E, 79, 2009, p. 026211) we considered Jacobi family (including Laguerre and Gaussian cases) of random matrix ensembles and reported exact solutions of crossover problems involving time-reversal symmetry breaking. In the present paper we give details of the work. We start with Dyson's Brownian motion description of random matrix ensembles and obtain universal hierarchic relations among the unfolded correlation functions. For arbitrary dimensions we derive the joint probability density (jpd) of eigenvalues for all transitions leading to unitary ensembles as equilibrium ensembles. We focus on the orthogonal-unitary and symplectic-unitary crossovers and give generic expressions for jpd of eigenvalues, two-point kernels and n-level correlation functions. This involves generalization of the theory of skew-orthogonal polynomials to crossover ensembles. We also consider crossovers in the circular ensembles to show the generality of our method. In the large dimensionality limit, correlations in spectra with arbitrary initial density are shown to be universal when expressed in terms of a rescaled symmetry breaking parameter. Applications of our crossover results to communication theory and quantum conductance problems are also briefly discussed.

Experimental Validation of Methanol Crossover in a Three-dimensional, Two-Fluid Model of a Direct Methanol Fuel Cell

DEFF Research Database (Denmark)

Olesen, Anders Christian; Berning, Torsten; Kær, Søren Knudsen

2012-01-01

A fully coupled three-dimensional, steady-state, two-fluid, multi-component and non-isothermal DMFC model has been developed in the commercial CFD package CFX 13 (ANSYS inc.). It accounts for the presence of micro porous layers, non-equilibrium phase change, and methanol and water uptake...... in the ionomer phase of the catalytic layer, and detailed membrane transport of methanol and water. In order to verify the models ability to predict methanol crossover, simulation results are compared with experimental measurements under different current densities along with air and methanol stoichiometries....... Methanol crossover is indirectly measured based on the combined anode and cathode exhaust CO2 mole fraction and by accounting for the CO2 production at the anode as a function of current density. This approach is simple and assumes that all crossed over methanol is oxidized. Moreover, it takes CO2...

Immediate acid-suppressing effects of ranitidine hydrochloride and rabeprazole sodium following initial administration and reintroduction: A randomized, cross-over study using wireless pH monitoring capsules.

Science.gov (United States)

Ono, Shouko; Kato, Mototsugu; Ono, Yuji; Imai, Aki; Yoshida, Takeshi; Shimizu, Yuichi; Asaka, Masahiro

2009-04-01

Histamine 2 receptor antagonists and proton-pump inhibitors, drugs that are widely used for the treatment of acid-related diseases, have different clinical characteristics. The objective of this study was to compare the acid-suppressing effects of ranitidine hydrochloride and those of rabeprazole sodium at the first administration and re-administration after withdrawal. The study was designed as an open-label, randomized, two-way cross-over trial. Seven Helicobacter pylori-negative healthy volunteers were enrolled in this study. Ranitidine hydrochloride (300 mg/day) or rabeprazole sodium (20 mg/day) was administered from days 1 to 7 and from days 11 to 13. The percentage of time with gastric pH sodium maintained a potent and stable effect from days 2 to 7 (ranitidine vs rabeprazole: P hydrochloride was attenuated after day 4. In addition, the effect of ranitidine hydrochloride at re-administration was attenuated (days 11, 12, and 13 vs pre-administration: not significant). In view of our observations, we expect symptoms associated with gastric acidity to be more adequately controlled with rabeprazole sodium in the short term when compared to ranitidine hydrochloride.

Bioequivalence study of two losartan tablet formulations with special emphasis on cardiac safety.

Science.gov (United States)

Khandave, Suhas S; Sawant, Satish V; Sahane, Rakhi V; Murthi, Vivekanand; Dhanure, Shivanand S; Surve, Pradeep G

2012-05-01

To study the bioequivalence of Losartan Potassium Tablets 50 mg manufactured by Micro Labs Ltd. India to Cozaar® Tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in normal healthy adult subjects under fasting condition along with the comparative safety evaluation of both treatments. The in vitro dissolution studies were carried out on 12 units each of test and reference products using the paddle method and dissolution media like water, 0.1 N hydrochloric acid with pH 1.2, pH 4.5 acetate buffer and pH 6.8 phosphate buffer. An open label, randomized, two-treatment, two-period, two-sequence, crossover bioequivalence study with a washout period of 7 days was conducted in 60 healthy Indian male subjects. Serial blood samples were collected after drug administration in each study period. Plasma concentrations of losartan and losartan acid were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of losartan and losartan acid were determined using a non compartmental model. Occurrence of adverse events, change in systolic blood pressure, diastolic blood pressure, heart rate and QT interval from the baseline to 3.50 h post dose were studied and compared between the two treatments as safety parameters. The in vitro study proved the essential similarity of both the formulations as evident from the similarity factor of > 50% in all the dissolution media. The ratios for geometric least square means and 90% confidence intervals were within the acceptance criteria of 80% to 125% for log transformed C(max), AUC(0-t) and AUC(0-∞) for losartan. No statistically significant difference between the two treatments was observed for either of the safety parameters. The test product Losartan Potassium tablets 50 mg manufactured by Micro Labs Limited, India was bioequivalent to Cozaar® tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in terms of rate and extent of absorption. Both treatments were well tolerated and had similar non

Escitalopram in painful polyneuropathy: A randomized, placebo-controlled, cross-over trial

DEFF Research Database (Denmark)

Otto, Marit; Bach, Flemming W; Jensen, Troels S

2008-01-01

Serotonin (5-HT) is involved in pain modulation via descending pathways in the central nervous system. The aim of this study was to test if escitalopram, a selective serotonin reuptake inhibitor (SSRI), would relieve pain in polyneuropathy. The study design was a randomized, double-blind, placebo......-controlled cross-over trial. The daily dose of escitalopram was 20mg once daily. During the two treatment periods of 5 weeks duration, patients rated pain relief (primary outcome variable) on a 6-point ordered nominal scale. Secondary outcome measures comprised total pain and different pain symptoms (touch...

Analysis of multi-step transitions in spin crossover nanochains

Energy Technology Data Exchange (ETDEWEB)

Chiruta, Daniel [GEMaC, Université de Versailles Saint-Quentin-en-Yvelines, CNRS-UVSQ (UMR 8635), 78035 Versailles Cedex (France); LISV, Université de Versailles Saint-Quentin-en-Yvelines, 78140 Velizy (France); Faculty of Electrical Engineering and Computer Science, Stefan cel Mare University, Suceava 720229 (Romania); Linares, Jorge, E-mail: jorge.linares@uvsq.fr [GEMaC, Université de Versailles Saint-Quentin-en-Yvelines, CNRS-UVSQ (UMR 8635), 78035 Versailles Cedex (France); Garcia, Yann, E-mail: yann.garcia@uclouvain.be [Institute of Condensed Matter and Nanosciences, Université Catholique de Louvain, Molecules, Solids and Reactivity (IMCN/MOST), Place Louis Pasteur, 1, 1348 Louvain-la-Neuve (Belgium); Dimian, Mihai [Faculty of Electrical Engineering and Computer Science, Stefan cel Mare University, Suceava 720229 (Romania); Dahoo, Pierre Richard [LATMOS, Université de Versailles-Saint-Quentin-en-Yvelines, CNRS-UPMC-UVSQ (UMR 8190), 78280 Guyancourt (France)

2014-02-01

The temperature driven phase transition occurring in spin crossover nanochains has been studied by an Ising-like model considering both short-range and long-range interactions. Various types of spin crossover profiles have been described in this framework, including a novel three-step transition identified in a nanosystem with eight molecules, which is modeled for the first time. A special interest has been also given to stepwise transitions accompanied by two hysteresis loops. The edge and size effects on spin crossover behavior have been investigated in order to get a deeper insight of the underlying mechanisms involved in these unusual spin transitions.

Green tea (Camellia sinensis) for patients with knee osteoarthritis: A randomized open-label active-controlled clinical trial.

Science.gov (United States)

Hashempur, Mohammad Hashem; Sadrneshin, Sara; Mosavat, Seyed Hamdollah; Ashraf, Alireza

2018-02-01

Green tea is known as a dietary supplement and a novel functional food worldwide. Since there are increasing preclinical evidence about efficacy of green tea for treating osteoarthritis, this study has aimed at assessing its efficacy and safety for patients with knee osteoarthritis. This is a randomized open-label active-controlled clinical trial. As many as fifty adults with osteoarthritis of knee were randomly allocated to receive the green tea extract (in dosage form of tablet) plus diclofenac tablet as "intervention group"; or: diclofenac tablet alone as "control group" for a period of four weeks. Patients were assessed at the beginning of intervention, and then 4 weeks later, in terms of pain score via visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire's total score in addition to its 3 sub-scores. Furthermore, they were asked about any adverse effects during intervention period. Mean differences of VAS pain, total WOMAC, and WOMAC physical function scores in green tea group showed a significant reduction, compared with the control group (P = 0.038, P = 0.006, and P = 0.004, respectively). However, No significant differences between the two groups were observed, regarding mean differences of WOMAC pain and stiffness scores of the enrolled patients (P = 0.163, and P = 0.150, respectively). Additionally, only 1 patient reported gastric upset [in control group]. It seems that green tea extract might well be considered as an adjunctive treatment both for control of pain and for the betterment of knee joint physical function in adults with osteoarthritis. However, further studies of longer duration and larger sample size are needed. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

A two-dimensional Fermi gas in the BEC-BCS crossover

Energy Technology Data Exchange (ETDEWEB)

Ries, Martin Gerhard

2016-01-21

This thesis reports on the preparation of a 2D Fermi gas in the BEC-BCS crossover and the observation of the BKT transition into a quasi long-range ordered superfluid phase. The pair momentum distribution of the gas is probed by means of a matter-wave focusing technique which relies on time-of-flight evolution in a weak harmonic potential. This distribution holds the coherence properties of the gas. The quasi long-range ordered phase manifests itself as a sharp low-momentum peak. The temperature where it forms is identified as the transition temperature. By tuning the temperature and the interaction strength, the phase diagram of the 2D Fermi gas in the BEC-BCS crossover is mapped out. The phase coherence is investigated in a self-interference experiment. Furthermore, algebraic decay of correlations is observed in the trap average of the first order correlation function, which is obtained from the Fourier transform of the pair momentum distribution. This is in qualitative agreement with predictions of homogeneous theory for the superfluid phase in a 2D gas. The presented results provide a foundation for future experimental and theoretical studies of strongly correlated 2D Fermi gases. They might thus help to elucidate complex systems such as the electron gas in high-T{sub c} superconductors.

Review of nutrition labeling formats.

Science.gov (United States)

Geiger, C J; Wyse, B W; Parent, C R; Hansen, R G

1991-07-01

This article examines nutrition labeling history as well as the findings of nine research studies of nutrition labeling formats. Nutrition labeling regulations were announced in 1973 and have been periodically amended since then. In response to requests from consumers and health care professionals for revision of the labeling system, the Food and Drug Administration initiated a three-phase plan for reform of nutrition labeling in 1990. President Bush signed the Nutrition Labeling and Education Act in November 1990. Literature analysis revealed that only nine studies with an experimental design have focused on nutrition labeling since 1971. Four were conducted before 1975, which was the year that nutrition labeling was officially implemented, two were conducted in 1980, and three were conducted after 1986. Only two of the nine studies supported the traditional label format mandated by the Code of Federal Regulations, and one study partially supported it. Four of the nine studies that evaluated graphic presentations of nutrition information found that consumer comprehension of nutrition information was improved with a graphic format for nutrition labeling: three studies supported the use of bar graphs and one study supported the use of a pie chart. Full disclosure (ie, complete nutrient and ingredient labeling) was preferred by consumers in two of the three studies that examined this variable. The third study supported three types of information disclosure dependent upon socioeconomic class. In those studies that tested graphics, a bar graph format was significantly preferred and showed better consumer comprehension than the traditional format.

The clinical meaningfulness of ADAS-Cog changes in Alzheimer's disease patients treated with donepezil in an open-label trial.

Science.gov (United States)

Rockwood, Kenneth; Fay, Sherri; Gorman, Mary; Carver, Daniel; Graham, Janice E

2007-08-30

In 6-month anti-dementia drug trials, a 4-point change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is held to be clinically important. We examined how this change compared with measures of clinical meaningfulness. This is a secondary analysis of a 12 month open-label study of 100 patients (71 women) diagnosed with mild to moderate AD treated with 5-10 mg of donepezil daily. We studied the observed case, 6-month change from baseline on the ADAS-Cog, the Clinician's Interview Based Impression of Change-Plus Caregiver Input (CIBIC-Plus), patient-Goal Attainment Scaling (PGAS) and clinician-GAS (CGAS). At 6 months, donepezil-treated patients (n = 95) were more likely to show no change (+/- 3 points) on the ADAS-Cog (56%) than to improve (20%) or decline (24%) by 4-points. ADAS-Cog change scores were little correlated with other measures: from -0.09 for PGAS to 0.27 for the CIBIC-Plus. While patients who improved on the ADAS-Cog were less likely to decline on the clinical measures (26%), 43% of patients who declined on the ADAS-Cog improved on at least two of the clinical measures. The ADAS-Cog did not capture all clinically important effects. In general, ADAS-Cog improvement indicates clinical improvement, whereas many people with ADAS-Cog decline do not show clinical decline. The open-label design of this study does not allow us to know whether this is a treatment effect, which requires further investigation.

Study of active crossover network | Tyona | Nigerian Journal of Physics

African Journals Online (AJOL)

An active crossover network system has been realized using an active component LF356 with a JFET input. The net work has two drives, the low frequency drive (Bass) and the high frequency drive (Treble). It employs high level crossover technique. The circuit performance was adequately verified and the frequency ...

Separable Crossover-Promoting and Crossover-Constraining Aspects of Zip1 Activity during Budding Yeast Meiosis.

Directory of Open Access Journals (Sweden)

Karen Voelkel-Meiman

2015-06-01

Full Text Available Accurate chromosome segregation during meiosis relies on the presence of crossover events distributed among all chromosomes. MutSγ and MutLγ homologs (Msh4/5 and Mlh1/3 facilitate the formation of a prominent group of meiotic crossovers that mature within the context of an elaborate chromosomal structure called the synaptonemal complex (SC. SC proteins are required for intermediate steps in the formation of MutSγ-MutLγ crossovers, but whether the assembled SC structure per se is required for MutSγ-MutLγ-dependent crossover recombination events is unknown. Here we describe an interspecies complementation experiment that reveals that the mature SC is dispensable for the formation of Mlh3-dependent crossovers in budding yeast. Zip1 forms a major structural component of the budding yeast SC, and is also required for MutSγ and MutLγ-dependent crossover formation. Kluyveromyces lactis ZIP1 expressed in place of Saccharomyces cerevisiae ZIP1 in S. cerevisiae cells fails to support SC assembly (synapsis but promotes wild-type crossover levels in those nuclei that progress to form spores. While stable, full-length SC does not assemble in S. cerevisiae cells expressing K. lactis ZIP1, aggregates of K. lactis Zip1 displayed by S. cerevisiae meiotic nuclei are decorated with SC-associated proteins, and K. lactis Zip1 promotes the SUMOylation of the SC central element protein Ecm11, suggesting that K. lactis Zip1 functionally interfaces with components of the S. cerevisiae synapsis machinery. Moreover, K. lactis Zip1-mediated crossovers rely on S. cerevisiae synapsis initiation proteins Zip3, Zip4, Spo16, as well as the Mlh3 protein, as do the crossovers mediated by S. cerevisiae Zip1. Surprisingly, however, K. lactis Zip1-mediated crossovers are largely Msh4/Msh5 (MutSγ-independent. This separation-of-function version of Zip1 thus reveals that neither assembled SC nor MutSγ is required for Mlh3-dependent crossover formation per se in budding yeast

Bioequivalence of Liposome-Entrapped Paclitaxel Easy-To-Use (LEP-ETU) formulation and paclitaxel in polyethoxylated castor oil: a randomized, two-period crossover study in patients with advanced cancer.

Science.gov (United States)

Slingerland, Marije; Guchelaar, Henk-Jan; Rosing, Hilde; Scheulen, Max E; van Warmerdam, Laurence J C; Beijnen, Jos H; Gelderblom, Hans

2013-12-01

Preclinical studies comparing paclitaxel formulated with polyethoxylated castor oil with the sonicated formulation of liposome-entrapped paclitaxel (LEP) have demonstrated that LEP was associated with reduced toxicity while maintaining similar efficacy. Preliminary studies on the pharmacokinetics in patients support earlier preclinical data, which suggested that the LEP Easy-to-Use (LEP-ETU) formulation and paclitaxel formulated with castor oil may have comparable pharmacokinetic properties. Our objectives were: (1) to determine bioequivalence of paclitaxel pharmaceutically formulated as LEP-ETU (test) and paclitaxel formulated with castor oil (reference); and (2) to assess the tolerability of LEP-ETU following intravenous administration. Patients with advanced cancer were studied in a randomized, 2-period crossover bioequivalence study. Patients received paclitaxel 175 mg/m(2) administered as an intravenous infusion over 180 minutes, either as a single-treatment cycle of the test formulation followed by a single-treatment cycle of the reference formulation, or vice versa. Thirty-two of 58 patients were evaluable and were included in the analysis for bioequivalence. Mean total paclitaxel Cmax values for the test and reference formulations were 4955.0 and 5108.8 ng/mL, respectively. Corresponding AUC0-∞ values were 15,853.8 and 18,550.8 ng·h/mL, respectively. Treatment ratios of the geometric means were 97% (90% CI, 91%-103%) for Cmax and 84% (90% CI, 80%-90%) for AUC0-∞. These results met the required 80% to 125% bioequivalence criteria. The most frequently reported adverse events after LEP-ETU administration were fatigue, alopecia, and myalgia. At the studied dose regimen, LEP-ETU showed bioequivalence with paclitaxel formulated with polyethoxylated castor oil. © 2013 Elsevier HS Journals, Inc. All rights reserved.

Popov approximation for composite bosons in the BCS-BEC crossover

International Nuclear Information System (INIS)

Pieri, P.; Strinati, G.C.

2005-01-01

Theoretical treatments of the BCS-BEC crossover need to provide as accurate as possible descriptions of the two regimes where the diluteness condition applies, either in terms of the constituent fermions (BCS limit) or of the composite bosons which form as bound-fermion pairs (BEC limit). This has to occur via a single fermionic theory that bridges across these two limiting representations. In this paper, we set up successive improvements of the fermionic theory, that result into composite bosons described at the level of either the Bogoliubov or the Popov approximations for pointlike bosons. This work bears on the recent experimental advances on the BCS-BEC crossover with trapped Fermi atoms, which show the need for accurate theoretical descriptions of the BEC side of the crossover

Food effect on the bioavailability of two distinct formulations of megestrol acetate oral suspension

Directory of Open Access Journals (Sweden)

Benoit Deschamps

2009-09-01

Full Text Available Benoit Deschamps1, Naomi Musaji2, John A Gillespie21SFBC Anapharm, Montreal, Canada; 2Strativa Pharmaceuticals, a division of Par Pharmaceutical, Inc., Woodcliff Lake, NJ, USAObjective: Megestrol acetate oral suspension (MAOS is an appetite stimulant indicated for cachexia in patients with AIDS. It is available in its original formulation, Megace® (MAOS, and as a nanocrystal dispersion, Megace® ES (MA-ES. Three studies were conducted to evaluate the pharmacokinetic properties of these formulations under fed and fasting conditions.Methods: An open-label, crossover trial was conducted in 24 healthy males randomized to MA-ES 625 mg/5 mL given with a high-calorie, high-fat meal, or after an overnight fast. Blood samples were drawn at multiple time points and pharmacokinetic parameters were determined. Two separate, open-label reference studies evaluated MAOS 800 mg/20 mL in 40 fed or 40 fasting healthy male volunteers.Results: In fasting MA-ES subjects, the average maximum concentration (Cmax was 30% less than the fed Cmax value. For MAOS, fasting Cmax was 86% less than fed Cmax. In fasting subjects, the area under the curve was 12,095 ng⋅h/mL for MA-ES, and 8,942 ng⋅h/mL for MAOS. In fed subjects, the absorption of the two formulations was comparable.Conclusion: Bioavailability and absorption are greater for MA-ES than MAOS in fasting subjects. MA-ES may be a preferred formulation of megestrol acetate when managing cachectic patients whose caloric intake is reduced.Keywords: megestrol acetate, bioavailability, cachexia, nanocrystal technology, appetite stimulant

Detection of Myoglobin with an Open-Cavity-Based Label-Free Photonic Crystal Biosensor.

Science.gov (United States)

Zhang, Bailin; Tamez-Vela, Juan Manuel; Solis, Steven; Bustamante, Gilbert; Peterson, Ralph; Rahman, Shafiqur; Morales, Andres; Tang, Liang; Ye, Jing Yong

2013-01-01

The label-free detection of one of the cardiac biomarkers, myoglobin, using a photonic-crystal-based biosensor in a total-internal-reflection configuration (PC-TIR) is presented in this paper. The PC-TIR sensor possesses a unique open optical microcavity that allows for several key advantages in biomolecular assays. In contrast to a conventional closed microcavity, the open configuration allows easy functionalization of the sensing surface for rapid biomolecular binding assays. Moreover, the properties of PC structures make it easy to be designed and engineered for operating at any optical wavelength. Through fine design of the photonic crystal structure, biochemical modification of the sensor surface, and integration with a microfluidic system, we have demonstrated that the detection sensitivity of the sensor for myoglobin has reached the clinically significant concentration range, enabling potential usage of this biosensor for diagnosis of acute myocardial infarction. The real-time response of the sensor to the myoglobin binding may potentially provide point-of-care monitoring of patients and treatment effects.

Structure and magnetic field of periodic permanent magnetic focusing system with open magnetic rings

International Nuclear Information System (INIS)

Peng Long; Li Lezhong; Yang Dingyu; Zhu Xinghua; Li Yuanxun

2011-01-01

The magnetic field along the central axis for an axially magnetized permanent magnetic ring was investigated by analytical and finite element methods. For open magnetic rings, both calculated and measured results show that the existence of the radial magnetic field creates a remarkable cosine distribution field along the central axis. A new structure of periodic permanent magnet focusing system with open magnetic rings is proposed. The structure provides a satisfactory magnetic field with a stable peak value of 120 mT for a traveling wave tube system. - Research highlights: → For open magnetic rings, both calculated and measured results show that the existence of the radial magnetic field creates a remarkable cosine distribution field along the central axis. → A new structure of periodic permanent magnet (PPM) focusing system with open magnetic rings is proposed. → The new PPM focusing system with open magnetic rings meets the requirements for TWT system.

Using a Montessori method to increase eating ability for institutionalised residents with dementia: a crossover design.

Science.gov (United States)

Lin, Li-Chan; Huang, Ya-Ju; Watson, Roger; Wu, Shiao-Chi; Lee, Yue-Chune

2011-11-01

To investigate the efficacy of applying a Montessori intervention to improve the eating ability and nutritional status of residents with dementia in long-term care facilities. An early intervention for eating difficulties in patients with dementia can give them a better chance of maintaining independence and reduce the risk of malnutrition. An experimental crossover design was employed. Twenty-nine residents were chosen from two dementia special care units in metropolitan Taipei. To avoid contamination between participants in units using both Montessori and control interventions, two dementia special care units were randomly assigned into Montessori intervention (I1) and routine activities (I2) sequence groups. A two-period crossover design was used, with 15 residents assigned to Montessori intervention sequence I (I1, I2) and 14 residents assigned to Montessori intervention sequence II (I2, I1). On each intervention day, residents were given their assigned intervention. Montessori intervention was provided in 30-min sessions once every day, three days per week, for eight weeks. There was a two-week washout period between each intervention. There was a significant reduction in the Edinburgh Feeding Evaluation in Dementia score for the Montessori intervention period but not for the routine activities period, while the mean differences for the Eating Behavior Scale score, self-feeding frequency and self-feeding time were significantly higher than those of the routine activities period. Except for the Mini-Nutritional Assessment score post-test being significantly less than the pre-test for the routine activities period, no significant differences for any other variables were found for the routine activities period. This study confirms the efficacy of a Montessori intervention protocol on eating ability of residents with dementia. Adopting Montessori intervention protocols to maintain residents' self-feeding ability in clinical practice is recommended. Montessori

The usefulness of two-port video-assisted thoracosopic surgery in low-risk patients with secondary spontaneous pneumothorax compared with open thoracotomy.

Science.gov (United States)

Park, Kyoung Taek

2014-01-01

Secondary spontaneous pneumothorax is difficult to treat and has been thought to have high morbidity and mortality rate due to the underlying diseases and presence of comorbidities in the patients. However, early surgical intervention will be beneficial if it is tolerable by the patient. In the surgical approach for treating pneumothorax, video-assisted thoracoscopic surgery (VATS) may reduce the postoperative drainage period and hospital stay compared with open thoracotomy. A retrospective review of the clinical data of 40 patients with secondary spontaneous pneumothorax who underwent open thoracotomy (n = 20) or two-port VATS (n = 20) between January 2008 and December 2012 was performed. Postoperative drainage period of open thoracotomy group and two-port VATS group was 9.85 ± 5.28 and 6.75 ± 2.45, respectively, with a significant inter-group difference. Postoperative hospital stay was 11.8 ± 5.12 in the open thoracotomy group and 8.25 ± 2.88 in the two-port VATS group, with a significant inter-group difference. Recurrence rate and postoperative complication rate were not significant between the two groups. In selected patients with secondary spontaneous pneumothorax treated with surgical approach, two-port VATS resulted in shorter postoperative drainage period and hospital stay compared with open thoracotomy.

Novel triphenylamine-cored two-photon absorbing dyes for labeling of biomolecules

International Nuclear Information System (INIS)

Xiao Haibo; Mei Chong; Wang Yaochuan; Li, Hui; Qian Shixiong; Yin Hongyao; Xu Zhisong

2011-01-01

Highlights: → Two novel triphenylamine-cored chromophores were synthesized. → These two dyes have sizable two-photon absorption cross-section at 800 nm. → They possess reasonable water solubility and are suitable as labels in aqueous biological environments. → These dyes have strong chelating ability. → They display a large set of reactivity for coupling to biomolecules. - Abstract: Two novel, V-shaped and Y-shaped dipicolinate derivatives branched from triphenylamine, {4-[(E)-2-(2,6-dimethoxycarbonylpyridin-4-yl)vinyl]}-N-phenyl-N-{4- [(E)-2-(2,6-dimethoxycarbonylpyridin-4-yl)vinylphenyl]}aniline (1) and {4-[(E)-2-(2,6-dimethoxycarbonylpyridin-4-yl) vinyl]}-N,N-bis {4-[(E)-2-(2,6-dimethoxycarbonyl pyridin-4-yl)vinylphenyl]}aniline (2) were synthesized. These compounds were designed for large two-photon absorption and in particular for labeling of biomolecules. Their linear absorption, fluorescence properties and their two-photon absorption properties as well as two-photon fluorescence cell imaging were examined. When excited at 800 nm, the two-photon absorption cross-section values of chromophores 1 and 2 in THF were 208 GM, 376 GM, respectively. These two-photon absorbing dyes possess reasonable water solubility, strong chelating ability and display a large set of reactivity for coupling to biomolecules, which are apparently due to the two methoxycarbonyl groups in pyridine ring. This work suggests that chromophores 1 and 2 are promising labels potentially applicable for the tracking of biomolecules using two-photon scanning microscopy.

Ocular discomfort responses after short periods of contact lens wear.

Science.gov (United States)

Papas, Eric; Tilia, Daniel; McNally, John; de la Jara, Percy Lazon

2015-06-01

To investigate if contact lens-related discomfort is a function of the time of day at which lenses are worn. This was a randomized, crossover, open-label clinical trial where subjective responses, with and without contact lenses, were assessed every 2 hours during five stages (A to E). Each stage began at the time when subjects would normally have inserted their contact lenses (T0). During stage A, no lenses were worn, whereas in stage B, lenses were worn continuously for 12 hours. In stages C to E, lenses were worn for only 4 hours. Contact lenses were inserted at T0 for stage C, but for stages D and E, lenses were not inserted until T0 + 4 and T0 + 8 hours, respectively. Mixed linear models were used for statistical analysis. In the absence of contact lenses, ocular comfort and dryness remained reasonably constant throughout the observation period. Ocular comfort and dryness decreased during 12 hours of continuous lens wear and became significantly worse from the 8-hour time onward compared with insertion (p 0.05) to the first 4 hours of continuous contact lens wear. Comparing the scores of each of these stages with the no-lens response at the corresponding time showed no significant differences for comfort (p > 0.23) or dryness (p > 0.37). Short periods of wear can be experienced at any time of day without significant change in ocular discomfort and dryness. This suggests that subjective responses at the end of the day are determined by the length of time lenses are in contact with the eye, rather than the time of day at which lenses are worn.

Preliminary evaluation of two radioiodinated maleimide derivatives targeting peripheral and membrane sulfhydryl groups for in vitro cell labeling

Energy Technology Data Exchange (ETDEWEB)

Amartey, John K., E-mail: amarjk48@hotmail.co [Cyclotron and Radiopharmaceuticals Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Parhar, Ranjit S. [Biological and Medical Research Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Shi, Yufei [Genetics Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Al-Mohanna, Futwan [Biological and Medical Research Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia)

2011-01-15

A factor impeding the advancement of cell mediated therapy is the inability to track these cells in vivo by noninvasive techniques. It has been shown that cells express high levels of sulfhydryl groups. We sought to explore these groups to covalently label cells with radiolabeled maleimide derivatives. Two maleimide derivatives; N-[2-(2,5-dioxoazolinyl)ethyl](5-iodo(3-pyridyl))carboxamide and N-[2-(2,5-dioxoazolinyl)ethyl](3-iodophenyl)carboxamide ([{sup 125}I]-4 and [{sup 125}I]-8) were synthesized and radioiodinated. These compounds were evaluated for in vitro binding to neutrophils, endothelial and mesenchymal stem cells, and biodistribution of the radiolabeled stem cells in nude mice. These radiotracers were obtained in moderate to high radiochemical yields. Binding to cells were moderate (20-60%/10{sup 6} cells) and the label was retained, although washout (an average of 18-55%) was observed depending on the cell type and the tracer used. The labeled cells initially localized in well perfused organs and at a later time showed a general distribution as expected. The novel tracers labeled several cell types and shown that the stability of the label and viability of the cells were maintained in vitro and in vivo for a reasonable period and warrant further in vivo investigation.

Comparative bioavailability of two formulations of sibutramine.

Science.gov (United States)

Franco Spínola, A C; Almeida, S; Filipe, A; Neves, R; Abolfathi, Z; Yritia, M; Anctil, D

2009-10-01

This study was conducted in order to compare the bioavailability of two capsule formulations containing 15 mg of sibutramine, N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N,N-dimethylamine hydrochloride monohydrate, 84485-00-7 CAS registry number. 62 healthy subjects were enrolled in a single-center, randomized, single-dose, open-label, 2-way crossover study, with a minimum washout period of 14 days. Plasma samples were collected up to 72.0 hours post-dosing. R-sibutramine, S-sibutramine, N-mono-desmethyl-sibutramine (M1) and N-di-desmethyl-sibutramine (M2) levels were determined by reverse liquid chromatography and detected by tandem mass spectrometry detection, LC/MS/MS method. Pharmacokinetic parameters used for bioequivalence assessment were the area under the concentration-time curve from time zero to time of last non-zero concentration (AUC0-t) and the maximum observed concentration (Cmax). These parameters were determined from sibutramine enantiomers as well from M1 and M2 concentration data using non-compartmental analysis. The 90% confidence intervals obtained by analysis of variance were 89.25 - 122.88% for Cmax, 90.37 - 123.18% for AUC0-t and 91.20 - 122.38% for AUCinf for R-sibutramine and 88.27 - 124.08% for Cmax, 86.15 - 121.78% for AUC0-t and 88.02 - 120.96% for AUCinf for S-sibutramine. These results were all within the range of 80.00 - 125.00% established by regulatory requirements. Bioequivalence between formulations was concluded both in terms of rate and extent of absorption.

Interference-mediated synaptonemal complex formation with embedded crossover designation

Science.gov (United States)

Zhang, Liangran; Espagne, Eric; de Muyt, Arnaud; Zickler, Denise; Kleckner, Nancy E.

2014-01-01

Biological systems exhibit complex patterns at length scales ranging from the molecular to the organismic. Along chromosomes, events often occur stochastically at different positions in different nuclei but nonetheless tend to be relatively evenly spaced. Examples include replication origin firings, formation of chromatin loops along chromosome axes and, during meiosis, localization of crossover recombination sites (“crossover interference”). We present evidence in the fungus Sordaria macrospora that crossover interference is part of a broader pattern that includes synaptonemal complex (SC) nucleation. This pattern comprises relatively evenly spaced SC nucleation sites, among which a subset are crossover sites that show a classical interference distribution. This pattern ensures that SC forms regularly along the entire length of the chromosome as required for the maintenance of homolog pairing while concomitantly having crossover interactions locally embedded within the SC structure as required for both DNA recombination and structural events of chiasma formation. This pattern can be explained by a threshold-based designation and spreading interference process. This model can be generalized to give diverse types of related and/or partially overlapping patterns, in two or more dimensions, for any type of object. PMID:25380597

Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder

Directory of Open Access Journals (Sweden)

Berlant Jeffrey L

2004-08-01

Full Text Available Abstract Background In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD. Methods Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5 or augmentation (n = 28. The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C score from baseline to 4 weeks, with response defined as a ≥ 30% reduction of PTSD symptoms. Results For those taking the PCL-C at both baseline and week 4 (n = 30, total symptoms declined by 49% at week 4 (paired t-test, P Conclusions Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials.

Crossover dynamics of dispersive shocks in Bose-Einstein condensates characterized by two- and three-body interactions

KAUST Repository

Crosta, M.; Trillo, S.; Fratalocchi, Andrea

2012-01-01

We show that the perturbative nonlinearity associated with three-atom interactions, competing with standard two-body repulsive interactions, can change dramatically the evolution of one-dimensional (1D) dispersive shock waves in a Bose-Einstein condensate. In particular, we prove the existence of a rich crossover dynamics, ranging from the formation of multiple shocks regularized by nonlinear oscillations culminating in coexisting dark and antidark matter waves to 1D-soliton collapse. For a given scattering length, all these different regimes can be accessed by varying the density of atoms in the condensate.

Crossover dynamics of dispersive shocks in Bose-Einstein condensates characterized by two- and three-body interactions

KAUST Repository

Crosta, M.

2012-04-10

We show that the perturbative nonlinearity associated with three-atom interactions, competing with standard two-body repulsive interactions, can change dramatically the evolution of one-dimensional (1D) dispersive shock waves in a Bose-Einstein condensate. In particular, we prove the existence of a rich crossover dynamics, ranging from the formation of multiple shocks regularized by nonlinear oscillations culminating in coexisting dark and antidark matter waves to 1D-soliton collapse. For a given scattering length, all these different regimes can be accessed by varying the density of atoms in the condensate.

Topical Coconut Oil in Very Preterm Infants: An Open-Label Randomised Controlled Trial.

Science.gov (United States)

Strunk, Tobias; Pupala, Sameer; Hibbert, Julie; Doherty, Dorota; Patole, Sanjay

2018-01-01

The immature fragile skin of preterm infants represents an inadequate protective barrier. The emollient and anti-infective properties of coconut oil make it a potentially beneficial topical agent for this population. Our aim was to evaluate feasibility, safety, and the effects of topical coconut oil on skin condition in very preterm infants. An open-label randomised controlled trial in preterm infants coconut oil (5 mL/kg) twice daily for 21 days, starting within 24 h of birth. The neonatal skin condition was the primary outcome, and was assessed using the Neonatal Skin Condition Score (NSCS) on days 1, 7, 14, and 21. The number of coconut oil applications was recorded to assess clinical feasibility and all enrolled infants were monitored for adverse effects of topical coconut application, such as skin irritation. A total of 72 infants born coconut oil was feasible and without adverse effects. The NSCS was maintained in the coconut oil group throughout the intervention period, but deteriorated from a median (IQR) of 3 (3-4) on day 1 to 4 (4-4) on day 21 in the control group (p = 0.01). There were no differences in common neonatal outcomes, including sepsis, necrotising enterocolitis, retinopathy of prematurity, chronic lung disease, and mortality. Topical coconut oil maintained a better skin condition in very preterm infants without adverse effects. This simple, safe, and affordable intervention warrants further investigation. © 2017 S. Karger AG, Basel.

10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension.

Science.gov (United States)

Bone, Henry G; Wagman, Rachel B; Brandi, Maria L; Brown, Jacques P; Chapurlat, Roland; Cummings, Steven R; Czerwiński, Edward; Fahrleitner-Pammer, Astrid; Kendler, David L; Lippuner, Kurt; Reginster, Jean-Yves; Roux, Christian; Malouf, Jorge; Bradley, Michelle N; Daizadeh, Nadia S; Wang, Andrea; Dakin, Paula; Pannacciulli, Nicola; Dempster, David W; Papapoulos, Socrates

2017-07-01

Long-term safety and efficacy of osteoporosis treatment are important because of the chronic nature of the disease. We aimed to assess the long-term safety and efficacy of denosumab, which is widely used for the treatment of postmenopausal women with osteoporosis. In the multicentre, randomised, double-blind, placebo-controlled, phase 3 FREEDOM trial, postmenopausal women aged 60-90 years with osteoporosis were enrolled in 214 centres in North America, Europe, Latin America, and Australasia and were randomly assigned (1:1) to receive 60 mg subcutaneous denosumab or placebo every 6 months for 3 years. All participants who completed the FREEDOM trial without discontinuing treatment or missing more than one dose of investigational product were eligible to enrol in the open-label, 7-year extension, in which all participants received denosumab. The data represent up to 10 years of denosumab exposure for women who received 3 years of denosumab in FREEDOM and continued in the extension (long-term group), and up to 7 years for women who received 3 years of placebo and transitioned to denosumab in the extension (crossover group). The primary outcome was safety monitoring, comprising assessments of adverse event incidence and serious adverse event incidence, changes in safety laboratory analytes (ie, serum chemistry and haematology), and participant incidence of denosumab antibody formation. Secondary outcomes included new vertebral, hip, and non-vertebral fractures as well as bone mineral density (BMD) at the lumbar spine, total hip, femoral neck, and one-third radius. Analyses were done according to the randomised FREEDOM treatment assignments. All participants who received at least one dose of investigational product in FREEDOM or the extension were included in the combined safety analyses. All participants who enrolled in the extension with observed data were included in the efficacy analyses. The FREEDOM trial (NCT00089791) and its extension (NCT00523341) are both

Early response to sibutramine in patients not meeting current label criteria: preliminary analysis of SCOUT lead-in period

DEFF Research Database (Denmark)

Caterson, Ian; Coutinho, Walmir; Finer, Nick

2010-01-01

The Sibutramine Cardiovascular Outcomes (SCOUT) trial protocol defines a patient population predominantly outside current European Union label criteria. This article explores responses to sibutramine during the 6-week, single-blind, lead-in period between patients who conformed to the label...... requirements ("conformers") and those who did not ("nonconformers"). SCOUT is an ongoing, randomized, double-blind, placebo-controlled outcome trial in overweight/obese patients at high risk of a cardiovascular event. In total, 10,742 patients received sibutramine and weight management during the lead...... with sibutramine confirms its good tolerability and efficacy in patients who meet current label criteria. Preliminary data from high-risk patients for whom sibutramine is currently contraindicated suggest a low discontinuation rate and few serious adverse events but confirmation from the SCOUT outcome data...

Crossover driven by time-reversal symmetry breaking in quantum chaos

International Nuclear Information System (INIS)

Taniguchi, N.; Hashimoto, A.; Simons, B.D.; Altshuler, B.L.

1994-01-01

Parametric correlations of the energy spectra of quantum chaotic systems are presented in the presence of time-reversal symmetry-breaking perturbations. The spectra disperse as a function of two external perturbations, one of which preserves time-reversal symmetry, while the other violates it. Exact analytical expressions for the parametric two-point autocorrelation function of the density of states are derived in the crossover region by means of the supermatrix method. For the orthogonal-unitary crossover, the velocity distribution is determined and shown to deviate from Gaussian. (orig.)

High-pressure water electrolysis: Electrochemical mitigation of product gas crossover

International Nuclear Information System (INIS)

Schalenbach, Maximilian; Stolten, Detlef

2015-01-01

Highlights: • New technique to reduce gas crossover during water electrolysis • Increase of the efficiency of pressurized water electrolysis • Prevention of safety hazards due to explosive gas mixtures caused by crossover • Experimental realization for a polymer electrolyte membrane electrolyzer • Discussion of electrochemical crossover mitigation for alkaline water electrolysis - Abstract: Hydrogen produced by water electrolysis can be used as an energy carrier storing electricity generated from renewables. During water electrolysis hydrogen can be evolved under pressure at isothermal conditions, enabling highly efficient compression. However, the permeation of hydrogen through the electrolyte increases with operating pressure and leads to efficiency loss and safety hazards. In this study, we report on an innovative concept, where the hydrogen crossover is electrochemically mitigated by an additional electrode between the anode and the cathode of the electrolysis cell. Experimentally, the technique was applied to a proton exchange membrane water electrolyzer operated at a hydrogen pressure that was fifty times larger than the oxygen pressure. Therewith, the hydrogen crossover was reduced and the current efficiency during partial load operation was increased. The concept is also discussed for water electrolysis that is operated at balanced pressures, where the crossover of hydrogen and oxygen is mitigated using two additional electrodes

Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial.

Science.gov (United States)

Arjyal, Amit; Basnyat, Buddha; Nhan, Ho Thi; Koirala, Samir; Giri, Abhishek; Joshi, Niva; Shakya, Mila; Pathak, Kamal Raj; Mahat, Saruna Pathak; Prajapati, Shanti Pradhan; Adhikari, Nabin; Thapa, Rajkumar; Merson, Laura; Gajurel, Damodar; Lamsal, Kamal; Lamsal, Dinesh; Yadav, Bharat Kumar; Shah, Ganesh; Shrestha, Poojan; Dongol, Sabina; Karkey, Abhilasha; Thompson, Corinne N; Thieu, Nga Tran Vu; Thanh, Duy Pham; Baker, Stephen; Thwaites, Guy E; Wolbers, Marcel; Dolecek, Christiane

2016-05-01

Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever. We did an open-label, randomised, controlled, superiority trial at two hospitals in the Kathmandu valley, Nepal. Eligible participants were children (aged 2-13 years) and adult (aged 14-45 years) with criteria for suspected enteric fever (body temperature ≥38·0°C for ≥4 days without a focus of infection). We randomly assigned eligible patients (1:1) without stratification to 7 days of either oral gatifloxacin (10 mg/kg per day) or intravenous ceftriaxone (60 mg/kg up to 2 g per day for patients aged 2-13 years, or 2 g per day for patients aged ≥14 years). The randomisation list was computer-generated using blocks of four and six. The primary outcome was a composite of treatment failure, defined as the occurrence of at least one of the following: fever clearance time of more than 7 days after treatment initiation; the need for rescue treatment on day 8; microbiological failure (ie, blood cultures positive for Salmonella enterica serotype Typhi, or Paratyphi A, B, or C) on day 8; or relapse or disease-related complications within 28 days of treatment initiation. We did the analyses in the modified intention-to-treat population, and subpopulations with either confirmed blood-culture positivity, or blood-culture negativity. The trial was powered to detect an increase of 20% in the risk of failure. This trial was registered at ClinicalTrials.gov, number NCT01421693, and is now closed. Between Sept 18, 2011, and July 14, 2014, we screened 725 patients for eligibility. On July 14, 2014, the trial was stopped early by the data safety and monitoring board because S Typhi strains with high-level resistance to

Introspecting into Deviance: Two Project Reports on Labeling Theory.

Science.gov (United States)

Posner, Judith

1979-01-01

Reports on two projects appropriate for undergraduate courses in the sociology of deviance, specifically courses emphasizing the labeling or symbolic interactionist perspective. The first project involves the use of confessional novels, and the second draws on the experiences of students regarding their own stigmas. (Author)

Pressure effect on hysteresis in spin-crossover solid materials

Energy Technology Data Exchange (ETDEWEB)

Gudyma, Iurii, E-mail: yugudyma@gmail.com [Department of General Physics, Chernivtsi National University, Chernivtsi 58012 (Ukraine); Ivashko, Victor [Department of General Physics, Chernivtsi National University, Chernivtsi 58012 (Ukraine); Dimian, Mihai [Department of Electrical and Computer Engineering, Howard University, Washington DC 20059 (United States); Faculty of Electrical Engineering and Computer Science & Integrated Center for Research, Development and Innovation in Advanced Materials, Nanotechnologies, and Distributed Systems for fabrication and control, Stefan cel Mare University, Suceava 720229 (Romania)

2016-04-01

A generalized microscopic Ising-like model is proposed to describe behavior of compressible spin-crossover solids with two states: low-spin and high-spin. The model was solved in mean-field approximation and shows hysteretic behavior at low energy difference between the states. We study the thermal transition between states under external hydrostatic pressure taking into account the changes in the volume of spin-crossover molecules in different states. Depending on the applied pressure, a spin-crossover system can have three types of behavior of molecular fraction in the high-spin state: hysteretic, second-order phase transition and no-phase transition. For the hysteretic regime, it is shown that the transition temperature under pressure is increased while the width of the hysteresis reduced.

Deuterium labeled cannabinoids

International Nuclear Information System (INIS)

Driessen, R.A.

1979-01-01

Complex reactions involving ring opening, ring closure and rearrangements hamper complete understanding of the fragmentation processes in the mass spectrometric fragmentation patterns of cannabinoids. Specifically labelled compounds are very powerful tools for obtaining more insight into fragmentation mechanisms and ion structures and therefore the synthesis of specifically deuterated cannabinoids was undertaken. For this, it was necessary to investigate the preparation of cannabinoids, appropriately functionalized for specific introduction of deuterium atom labels. The results of mass spectrometry with these labelled cannabinoids are described. (Auth.)

ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes.

Directory of Open Access Journals (Sweden)

Marco Barchi

2008-05-01

Full Text Available During meiosis in most sexually reproducing organisms, recombination forms crossovers between homologous maternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division. The number and distribution of crossovers are tightly controlled, but the factors that contribute to this control are poorly understood in most organisms, including mammals. Here we provide evidence that the ATM kinase or protein is essential for proper crossover formation in mouse spermatocytes. ATM deficiency causes multiple phenotypes in humans and mice, including gonadal atrophy. Mouse Atm-/- spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm(-/- meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meiotic metaphase I. Strikingly, Spo11+/-Atm-/- spermatocytes are defective in forming the obligate crossover on the sex chromosomes, even though the XY pair is usually incorporated in a sex body and is transcriptionally inactivated as in normal spermatocytes. The XY crossover defect correlates with the appearance of lagging chromosomes at metaphase I, which may trigger the extensive metaphase apoptosis that is observed in these cells. In addition, control of the number and distribution of crossovers on autosomes appears to be defective in the absence of ATM because there is an increase in the total number of MLH1 foci, which mark the sites of eventual crossover formation, and because interference between MLH1 foci is perturbed. The axes of autosomes exhibit structural defects that correlate with the positions of ongoing recombination. Together, these findings indicate that ATM plays a role in both crossover control and chromosome axis integrity and further suggests that ATM is important for coordinating these features of meiotic chromosome dynamics.

Single-crossover recombination in discrete time.

Science.gov (United States)

von Wangenheim, Ute; Baake, Ellen; Baake, Michael

2010-05-01

Modelling the process of recombination leads to a large coupled nonlinear dynamical system. Here, we consider a particular case of recombination in discrete time, allowing only for single crossovers. While the analogous dynamics in continuous time admits a closed solution (Baake and Baake in Can J Math 55:3-41, 2003), this no longer works for discrete time. A more general model (i.e. without the restriction to single crossovers) has been studied before (Bennett in Ann Hum Genet 18:311-317, 1954; Dawson in Theor Popul Biol 58:1-20, 2000; Linear Algebra Appl 348:115-137, 2002) and was solved algorithmically by means of Haldane linearisation. Using the special formalism introduced by Baake and Baake (Can J Math 55:3-41, 2003), we obtain further insight into the single-crossover dynamics and the particular difficulties that arise in discrete time. We then transform the equations to a solvable system in a two-step procedure: linearisation followed by diagonalisation. Still, the coefficients of the second step must be determined in a recursive manner, but once this is done for a given system, they allow for an explicit solution valid for all times.

Audiovisual distraction for pain relief in paediatric inpatients: A crossover study.

Science.gov (United States)

Oliveira, N C A C; Santos, J L F; Linhares, M B M

2017-01-01

Pain is a stressful experience that can have a negative impact on child development. The aim of this crossover study was to examine the efficacy of audiovisual distraction for acute pain relief in paediatric inpatients. The sample comprised 40 inpatients (6-11 years) who underwent painful puncture procedures. The participants were randomized into two groups, and all children received the intervention and served as their own controls. Stress and pain-catastrophizing assessments were initially performed using the Child Stress Scale and Pain Catastrophizing Scale for Children, with the aim of controlling these variables. The pain assessment was performed using a Visual Analog Scale and the Faces Pain Scale-Revised after the painful procedures. Group 1 received audiovisual distraction before and during the puncture procedure, which was performed again without intervention on another day. The procedure was reversed in Group 2. Audiovisual distraction used animated short films. A 2 × 2 × 2 analysis of variance for 2 × 2 crossover study was performed, with a 5% level of statistical significance. The two groups had similar baseline measures of stress and pain catastrophizing. A significant difference was found between periods with and without distraction in both groups, in which scores on both pain scales were lower during distraction compared with no intervention. The sequence of exposure to the distraction intervention in both groups and first versus second painful procedure during which the distraction was performed also significantly influenced the efficacy of the distraction intervention. Audiovisual distraction effectively reduced the intensity of pain perception in paediatric inpatients. The crossover study design provides a better understanding of the power effects of distraction for acute pain management. Audiovisual distraction was a powerful and effective non-pharmacological intervention for pain relief in paediatric inpatients. The effects were

A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

International Nuclear Information System (INIS)

Mason, Jay W; Moon, Thomas E; O’Boyle, Erin; Dietz, Albert

2014-01-01

Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO), intravenous (IV), and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC) injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals. This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF) for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated. The upper one-sided 95% confidence interval (CI) for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36) at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours) and slow elimination (mean half-life 18.6 hours; systemic clearance 20.2 L/hour) of granisetron versus the expected early peak concentration and elimination of granisetron IV. APF530 SC was well tolerated. Adverse events, most commonly constipation and SC injection-site reactions, were generally mild and quickly resolved. APF530 1 g SC did

The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial.

Science.gov (United States)

Berk, Michael; Dean, Olivia; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa S; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Allwang, Christine; Cobb, Heidi; Bush, Ashley I; Schapkaitz, Ian; Dodd, Seetal; Malhi, Gin S

2011-12-01

Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders, including bipolar disorder. This dysregulation may be amenable to therapeutic intervention. Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain, and the most generic of all endogenous antioxidants in terms of action. N-acetylcysteine (NAC) is a glutathione precursor that effectively replenishes brain glutathione. Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy, and the limited efficacy of mood stabilisers in the depressive phase of the disorder, this is a major unmet need. This study reports data on the treatment of 149 individuals with moderate depression during the 2 month open label phase of a randomised placebo controlled clinical trial of the efficacy of 1g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder. In this trial, the estimated mean baseline Bipolar Depression Rating Scale (BDRS) score was 19.7 (SE=0.8), and the mean BDRS score at the end of the 8 week open label treatment phase was 11.1 (SE=0.8). This reduction was statistically significant (pdepression scores with NAC treatment. Large placebo controlled trials of acute bipolar depression are warranted. Copyright © 2011 Elsevier B.V. All rights reserved.

Diclofenac systemic bioavailability of a topical 1% diclofenac + 3% menthol combination gel vs. an oral diclofenac tablet in healthy volunteers: a randomized, open-label, crossover study
.

Science.gov (United States)

Moreira, Sebastian A; Liu, D Jeffery

2017-04-01

Evaluate systemic exposure with repeated topical application of a fixed-combination topical gel product containing 1% diclofenac sodium and 3% menthol in either of 2 formulation packages relative to oral administration. In this phase 1, single-center, 4-way crossover study, healthy volunteers aged 18 - 50 years underwent consecutive 3-day treatment regimens in a randomly assigned sequence with each of 4 treatment groups: 4 g of topical 1% diclofenac + 3% menthol gel administered via an aluminum tube or roll-on device applied 4 times daily; 4 g of topical 1% diclofenac sodium gel (Voltaren Gel) applied 4 times daily; and oral diclofenac sodium tablets 50 mg 3 times daily. Treatment regimens were separated by 2-day washout periods. A total of 18 subjects enrolled and completed the study. Relative to oral administration, area under the concentration time curve from 48 to 72 hours (AUC48-72) with topical administration of 1% diclofenac + 3% menthol gel from a tube or roll-on device was 16.1% (90% CI: 12.2 - 21.1%) and 14.4% (90% CI: 11.0 - 19.0%), respectively. The diclofenac/menthol combination delivered significantly higher exposures of diclofenac compared with Voltaren Gel. A higher number of adverse events (AEs) occurred with the topical diclofenac/menthol combination (61%) vs. Voltaren Gel (22%) or oral diclofenac (6%); most were local skin reactions. No difference in systemic AEs was observed among the groups. As expected, systemic exposure was significantly lower with the topical diclofenac/menthol treatment regimens compared with oral diclofenac. Local skin AEs were increased with the topical combination product, but the risk of systemic AEs was low.
.

Intravenous immunoglobulin for maintenance treatment of multifocal motor neuropathy: A multi-center, open-label, 52-week phase 3 trial.

Science.gov (United States)

Kuwabara, Satoshi; Misawa, Sonoko; Mori, Masahiro; Iwai, Yuta; Ochi, Kazuhide; Suzuki, Hidekazu; Nodera, Hiroyuki; Tamaoka, Akira; Iijima, Masahiro; Toda, Tatsushi; Yoshikawa, Hiroo; Kanda, Takashi; Sakamoto, Ko; Kusunoki, Susumu; Sobue, Gen; Kaji, Ryuji

2018-04-10

Intravenous immunoglobulin (IVIg) therapy is currently the only established treatment in patients with multifocal motor neuropathy (MMN), and many patients have an IVIg-dependent fluctuation. We aimed to investigate the efficacy and safety of every 3 week IVIg (1.0 g/kg) for 52 weeks. This study was an open-label phase 3 clinical trial, enrolling 13 MMN patients. After an induction IVIg therapy (0.4 g/kg/d for 5 consecutive days), maintenance dose (1.0 g/kg) was given every 3 weeks for 52 weeks. The major outcome measures were the Medical Research Council (MRC) sum score and hand-grip strength at week 52. This trial is registered with ClinicalTrials.gov, number NCT01827072. At week 52, 11 of the 13 patients completed the study, and all 11 had a sustained improvement. The mean (SD) MRC sum score was 85.6 (8.7) at the baseline, and 90.6 (12.8) at week 52. The mean grip strength was 39.2 (30.0) kPa at the baseline and 45.2 (32.8) kPa at week 52. Two patients dropped out because of adverse event (dysphagia) and decision of an investigator, respectively. Three patients developed coronary spasm, dysphagia, or inguinal herniation, reported as the serious adverse events, but considered not related with the study drug. The other adverse effects were mild and resolved by the end of the study period. Our results show that maintenance treatment with 1.0 g/kg IVIg every 3 week is safe and efficacious for MMN patients up to 52 weeks. Further studies are required to investigate optimal dose and duration of maintenance IVIg for MMN. © 2018 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals, Inc. on behalf of Peripheral Nerve Society.

Periodic and stochastic thermal modulation of protein folding kinetics.

Science.gov (United States)

Platkov, Max; Gruebele, Martin

2014-07-21

Chemical reactions are usually observed either by relaxation of a bulk sample after applying a sudden external perturbation, or by intrinsic fluctuations of a few molecules. Here we show that the two ideas can be combined to measure protein folding kinetics, either by periodic thermal modulation, or by creating artificial thermal noise that greatly exceeds natural thermal fluctuations. We study the folding reaction of the enzyme phosphoglycerate kinase driven by periodic temperature waveforms. As the temperature waveform unfolds and refolds the protein, its fluorescence color changes due to FRET (Förster resonant Energy Transfer) of two donor/acceptor fluorophores labeling the protein. We adapt a simple model of periodically driven kinetics that nicely fits the data at all temperatures and driving frequencies: The phase shifts of the periodic donor and acceptor fluorescence signals as a function of driving frequency reveal reaction rates. We also drive the reaction with stochastic temperature waveforms that produce thermal fluctuations much greater than natural fluctuations in the bulk. Such artificial thermal noise allows the recovery of weak underlying signals due to protein folding kinetics. This opens up the possibility for future detection of a stochastic resonance for protein folding subject to noise with controllable amplitude.

Consumption of organic diets does not affect intake and absorption of zinc and copper in men-evidence from two cross-over trials

DEFF Research Database (Denmark)

Mark, Alicja Budek; Kápolna, Emese; Laursen, Kristian H.

2013-01-01

diets on intake and absorption of zinc and copper in men. Two double-blinded, cross-over, intervention trials (3 dietary periods of 12 days with 2-week-long wash-out) were performed in 2008 (n = 17) and 2009 (n = 16) in young men. The diets were based on 9 crops grown in rigidly controlled organic......Agricultural methods may affect the nutritional composition of plants and cause complex changes in the food matrix. Whether this affects the dietary absorption of minerals that are important for maintaining health thorough life remains unclear. We compared the effects of organic and conventional......; 12.35 ± 0.47 mg per 10 MJ and 44.6% ± 12.1, respectively) and copper (overall mean ± SD; 2.12 ± 0.28 mg per 10 MJ and 41.2% ± 13.2, respectively) were not different between the organic and conventional diets. The growing season had no effect on zinc intake and absorption, but the copper intake...

Modular invariance, universality and crossover in the quantum Hall effect

International Nuclear Information System (INIS)

Dolan, Brian P.

1999-01-01

An analytic form for the conductivity tensor in crossover between two quantum Hall plateaux is derived, which appears to be in good agreement with existing experimental data. The derivation relies on an assumed symmetry between quantum Hall states, a generalisation of the law of corresponding states from rational filling factors to complex conductivity, which has a mathematical expression in terms of an action of the modular group on the upper-half complex conductivity plane. This symmetry implies universality in quantum Hall crossovers. The assumption that the β-function for the complex conductivity is a complex analytic function, together with some experimental constraints, results in an analytic expression for the crossover, as a function of the external magnetic field

Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

Science.gov (United States)

Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

2013-01-01

Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found between…

Periodicals Price Survey 2008: Embracing Openness

Science.gov (United States)

Van Orsdel, Lee C.; Born, Kathleen

2008-01-01

Evidence for open access as an emergent, global state of mind is everywhere. The "New York Times" went "open" last September, and the "Wall Street Journal" is slated to follow. Increasingly, scholarly communities are breaking with tradition and calling for the open sharing of research, software, and data. Amongst these global initiatives is the…

Music exposure and maturation of late preterm sleep-wake cycles: a randomised crossover trial.

Science.gov (United States)

Stokes, Adia; Agthe, Alexander G; El Metwally, Dina

2018-04-01

To determine the effect of music on sleep-wake cycle (SWC) patterns in late preterm neonates. In a masked crossover study, infants between 32 and 36 6/7 weeks gestation were randomised to music exposure either during the first six or last six hours of a 12-hour observation period. SWC characteristics were determined by continuous amplitude-integrated electroencephalography (aEEG) read by two coders masked to exposure sequence. Analysis was performed in paired comparisons. ANOVA was used to assess the effects of music exposure, period and crossover on SWC outcomes: (i) Burdjalov Scores (BS) during active sleep (AS) (ii) per cent and duration of quiet sleep (QS). Thirty infants were studied. A total of 222 QS cycles (median seven per patient; range five to 12) were analysed. Music exposure was associated with higher BS (F = 10.60, p = 0.0019) in AS and decreased interruptions during QS. The advanced postconceptual age (PCA) SWC pattern during AS was equivalent to a one-week mean. Number, duration and ratio of QS cycles did not change with music exposure. Music exposure elicits an increasing PCA pattern in AS and fewer interruptions in QS. Music may benefit sleep in late preterm infants. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Effect of benzalkonium chloride?free travoprost on intraocular pressure and ocular surface symptoms in patients with glaucoma previously on latanoprost: an open-label study

OpenAIRE

Lopes, Joao F.; Hubatsch, Douglas A.; Amaris, Patricia

2015-01-01

Background Prostaglandin analogs reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension; however, these medications may affect the ocular surface and elicit ocular discomfort when preserved with benzalkonium chloride (BAK). Methods This was an open-label, single-arm study conducted in Latin America from February 2012 to May 2013. Patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost 0.005?% were transitioned to recei...

Open-label study of donepezil in traumatic brain injury.

Science.gov (United States)

Masanic, C A; Bayley, M T; VanReekum, R; Simard, M

2001-07-01

To determine preliminarily whether donepezil will improve memory, behavior, and global function after chronic traumatic brain injury (TBI). Sixteen-week open-label study. Outpatient TBI rehabilitation program. Four patients with chronic, severe TBI. Donepezil 5mg daily for 8 weeks followed by 10mg daily for 4 weeks. Memory measures included the Rey Auditory Verbal Learning Test (RAVLT), the Complex Figure Test (CFT), items from the Rivermead Behavioural Memory Test (RBMT), and a semantic fluency task. The Neuropsychiatric Inventory (NPI) evaluated behavior and affect. Function was assessed by using the FIM instrument and a clinical global impression of change. On the RAVLT, the mean scores for learning and short- and long-term recall improved by 0.4, 1.04, and.83 standard deviations (SDs) above baseline, respectively. On the CFT, the mean scores for short-term recall and long-term recall improved by 1.56 and 1.38 SDs above baseline, respectively. A positive trend was observed on the RBMT and on the NPI subscales. Donepezil may improve some aspects of memory and behavior in persons with chronic TBI. Randomized clinical trials are required to support these preliminary findings. Copyright 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Optimal design of work zone median crossovers.

Science.gov (United States)

2010-09-01

The use of temporary median crossovers in work zones allows for the closure of one side of a multi-lane roadway while : maintaining two-way traffic on the opposite side. This process provides the ability for construction and maintenance crews : to co...

Risk of injury after alcohol consumption from case-crossover studies in five countries from the America’s

Science.gov (United States)

Borges, Guilherme; Orozco, Ricardo; Monteiro, Maristela; Cherpitel, Cheryl; Then, Eddy Pérez; López, Víctor A.; Bassier-Paltoo, Marcia; Weil A., Donald; de Bradshaw, Aldacira M

2012-01-01

Aims This study aimed to: 1) provide relative risk (RR) estimates between acute alcohol use and injuries from emergency departments in the Dominican Republic, Guatemala, Guyana, Nicaragua and Panama, and 2) test whether the RR differs if two control periods for the estimates were used. Design Case-crossover methodology was used to obtain estimates of the RR of having an injury within six hours after drinking alcohol, using a pair-matching design with control periods of the same time of day the day prior to injury, and the same time of day and day of week the week prior to injury. Setting Emergency departments(EDs). Participants 2,503 injured patients from EDs were interviewed between 2010–2011, with a response rate of 92.6%. Measurements Number of drinks consumed within six hours prior to the injury and in the two control periods. Findings The RR of injury after drinking alcohol was 4.38 (95% confidence interval CI= 3.29–5.84) using as the control period the prior week, and 5.35 (CI=3.50–8.17) using as a control period the prior day. The RR was 5.08 (CI=4.15–6.23) in multiple matching. Those drinking 1–2 drinks had a RR of 4.85 (CI=3.12–7.54); those drinking 3–5 a RR of 5.00 (CI =3.47–7.18); those drinking 6–15 a RR of 4.54 (CI=3.36–6.14); and those drinking 16 or more a RR of 10.42 (CI=4.38–24.79). Conclusions As in other countries, alcohol drinking is a trigger for an injury in all five countries. The use of more than one control period give further strength to these findings from case-crossover analysis. PMID:22775508

The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol

OpenAIRE

Tanner, Trevor; Aspley, Sue; Munn, Andrew; Thomas, Tracy

2010-01-01

Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Methods Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-...

Effect of browned and unbrowned corn products intrinsically labeled with 65Zn on absorption of 65Zn in humans

International Nuclear Information System (INIS)

Lykken, G.I.; Mahalko, J.; Johnson, P.E.; Milne, D.; Sandstead, H.H.; Garcia, W.J.; Dintzis, F.R.; Inglett, G.E.

1986-01-01

Experimental browned and unbrowned corn products were formulated and processed from unenriched, degermed yellow corngrits. The browned product (cornflakes) contained more insoluble dietary fiber and bound more zinc (in vitro) than the unbrowned product (corngrits). During processing some of the cornflakes and corngrits were combined with a small amount of yellow corn endospermhull intrinsically labeled with 65 Zn. The intrinsically labeled corn products were fed, in a crossover design, as components of two breakfasts to six normal, unconfined volunteers. Each volunteer absorbed more 65 Zn from the corngrits than from the cornflakes. The reduced 65 Zn absorption from cornflakes was attributed to heating and toasting reaction products, possibly Maillard, which bound zinc and consequently made the zinc less available for absorption

Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.

Science.gov (United States)

Rosenberg, Evan C; Louik, Jay; Conway, Erin; Devinsky, Orrin; Friedman, Daniel

2017-08-01

Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9-point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure-reducing effects; however, further studies in placebo-controlled, double-blind trials are necessary to confirm this finding. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

75 FR 81948 - Use of Various Winemaking Terms on Wine Labels and in Advertisements; Comment Period Extension

Science.gov (United States)

2010-12-29

...In response to a request made on behalf of a wine industry association, TTB is extending for an additional 60 days the comment period prescribed in Notice No. 109, Use of Various Winemaking Terms on Wine Labels and in Advertisements; Request for Public Comment, an advance notice of proposed rulemaking published in the Federal Register on November 3, 2010.

Patient-reported outcomes in patients with overactive bladder treated with mirabegron and tolterodine in a prospective, double-blind, randomized, two-period crossover, multicenter study (PREFER).

Science.gov (United States)

Herschorn, Sender; Staskin, David; Tu, Le Mai; Fialkov, Jonathan; Walsh, Terry; Gooch, Katherine; Schermer, Carol R

2018-04-19

The PREFER study was an assessment of medication tolerability, treatment preference and symptom improvement during treatment with mirabegron (M) and tolterodine (T) extended release (ER) in patients with overactive bladder (OAB). In this analysis of PREFER, patient-reported outcomes (PROs) were assessed during treatment. PREFER was a two-period, 8-week crossover, double-blind, phase IV study (NCT02138747) of treatment-naïve adults with OAB ≥3 months randomized to 1 of 4 treatment sequences (M/T; T/M; M/M; T/T), separated by a 2-week washout. Tolterodine ER was dosed at 4 mg for 8 weeks and mirabegron was dosed at 25 mg for 4 weeks then increased to 50 mg for the next 4 weeks. At each visit, PROs related to treatment satisfaction, quality of life and symptom bother were assessed using the OAB Satisfaction (OAB-S; 3 independent scales/5 single-item overall assessments), OAB-q (total health-related QoL [HRQoL] and subscales [Sleep, Social, Coping, Concern] and Symptom Bother scale) and Patient Perception of Bladder Condition (PPBC) questionnaires. Responder rates were reported for OAB-q subscales based on a minimal important difference (MID; ≥ 10-point improvement) and OAB-S Medication Tolerability score ≥ 90. In total, 358 randomized patients received ≥1 dose of double-blind study medication and completed ≥1 post-baseline value (OAB-S scale, OAB-q, PPBC): M/T (n = 154), T/M (n = 144), M/M (n = 30) or T/T (n = 30). At end of treatment (EoT), mirabegron and tolterodine ER were associated with similar mean improvements in 7 of the 8 OAB-S scores investigated, OAB-q scales and PPBC. A higher percentage of patients achieved clinically relevant improvements (MID) in OAB-q scales and OAB-S Medication Tolerability score during treatment with mirabegron than tolterodine ER. On average, patients with OAB experienced improvements in treatment satisfaction, HRQoL and symptom bother that were of a similar magnitude during treatment with

Dimensional crossover in fluids under nanometer-scale confinement.

Science.gov (United States)

Das, Amit; Chakrabarti, J

2012-05-01

Several earlier studies have shown signatures of crossover in various static and dynamics properties of a confined fluid when the confining dimension decreases to about a nanometer. The density fluctuations govern the majority of such properties of a fluid. Here, we illustrate the crossover in density fluctuation in a confined fluid, to provide a generic understanding of confinement-induced crossover of fluid properties, using computer simulations. The crossover can be understood as a manifestation of changes in the long-wavelength behavior of fluctuation in density due to geometrical constraints. We further show that the confining potential significantly affects the crossover behavior.

Evaluation of doubly labeled water for measuring energy expenditure during changing nutrition

International Nuclear Information System (INIS)

Jones, P.J.; Winthrop, A.L.; Schoeller, D.A.; Filler, R.M.; Swyer, P.R.; Smith, J.; Heim, T.

1988-01-01

Change in abundance of 2 H and 18 O in dietary water during a doubly labeled water energy period may introduce error into the calculated carbon dioxide production rate (RCO 2 ). To examine the accuracy of 2 H 2 ( 18 )O during changing nutritional regimens, we compared 2 H 2 ( 18 )O and periodic open-circuit respiratory gas exchange (RGE) in postsurgical infants who were changing from parenteral to alternative parenteral and/or oral nutrition. The two methods were compared before and after correction for shifts in isotopic abundance of the infant water pools during the energy-expenditure period. Baseline corrections were predicted using the difference between abundances of the initial body water and final nutrient solutions. Before isotopic correction, 2 H 2 ( 18 )O underestimated RCO 2 in eight subjects by 11.8 +/- 20.1% (mean +/- SD). After correction, agreement between the two methods improved; the underestimate was then -8.7 +/- 12.9%. To obtain maximum precision of 2 H 2 ( 18 )O, subjects should be maintained on the same nutritional regimen before and during the study unless valid correction formulae are used

Crossover of coherent Rabi oscillations in graphene

International Nuclear Information System (INIS)

Enamullah; Kumar, Vipin; Setlur, Girish S.

2012-01-01

We study the phenomenon of crossover of Rabi oscillations in graphene as a function of detuning - the difference between the frequency of the incident wave and interband energy (2v F |k|). It is shown by comparison with an exactly solved model with bands having linear dispersion but lacking pseudospin that this crossover is unique to graphene, attributable to the pseudospin character of the graphene hamiltonian. A group theoretic argument for why this model is solvable is given. We compute the nonlinear current using our formalism, the main prediction being the threshold behavior (with exponent equal to 1/2) of the slowly varying part of the current in frequency domain with threshold frequency being 2ω R 2 /ω (‘anomalous’ Rabi frequency) where ω R is the Rabi frequency for zero detuning. The novelty of our approach is the introduction of an alternative to the rotating wave approximation (RWA) (called asymptotic RWA here) which is argued to be important in demonstrating this crossover. We provide an interpolation method between these two regimes, that shows novel phenomena attributable to harmonic generation. A fully numerical solution to the Bloch equations verifies the analytical results and the various approximation schemes.

Stationary states of two-level open quantum systems

International Nuclear Information System (INIS)

Gardas, Bartlomiej; Puchala, Zbigniew

2011-01-01

A problem of finding stationary states of open quantum systems is addressed. We focus our attention on a generic type of open system: a qubit coupled to its environment. We apply the theory of block operator matrices and find stationary states of two-level open quantum systems under certain conditions applied on both the qubit and the surrounding.

On-target labeling of intracellular metabolites combined with chemical mapping of individual hyphae revealing cytoplasmic relocation of isotopologues.

Science.gov (United States)

Hu, Jie-Bi; Chen, Yu-Chie; Urban, Pawel L

2012-06-05

A microscale analytical platform integrating microbial cell culture, isotopic labeling, along with visual and mass spectrometric imaging with single-cell resolution has been developed and applied in the monitoring of cellular metabolism in fungal mycelium. The method implements open chips with a two-dimensional surface pattern composed of hydrophobic and hydrophilic zones. Two hydrophilic islands are used as medium reservoirs, while the hydrophobic area constitutes the support for the growing aerial hyphae, which do not have direct contact with the medium. The first island, containing (12)C(6)-glucose medium, was initially inoculated with the mycelium (Neurospora crassa), and following the initial incubation period, the hyphae progressed toward the second medium island, containing an isotopically labeled substrate ((13)C(6)-glucose). The (13)C atoms were gradually incorporated into cellular metabolites, which was revealed by MALDI-MS. The fate of the chitin-biosynthesis precursor, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), was monitored by recording mass spectra with characteristic isotopic patterns, which indicated the presence of various (12)C/(13)C isotopologues. The method enabled mapping the (13)C-labeled UDP-GlcNAc in fungal mycelium and recording its redistribution in hyphae, directly on the chip.

An open-label naturalistic pilot study of acamprosate in youth with autistic disorder.

Science.gov (United States)

Erickson, Craig A; Early, Maureen; Stigler, Kimberly A; Wink, Logan K; Mullett, Jennifer E; McDougle, Christopher J

2011-12-01

To date, placebo-controlled drug trials targeting the core social impairment of autistic disorder (autism) have had uniformly negative results. Given this, the search for new potentially novel agents targeting the core social impairment of autism continues. Acamprosate is U.S. Food and Drug Administration-approved drug to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid and glutamate neurotransmission. This study describes our initial open-label experience with acamprosate targeting social impairment in youth with autism. In this naturalistic report, five of six youth (mean age, 9.5 years) were judged treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only mild gastrointestinal adverse effects noted in three (50%) subjects.

Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial

Directory of Open Access Journals (Sweden)

Subha V. Raman

2017-02-01

Full Text Available Abstract Background Cardiomyopathy is a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD. We recently showed in a 12-month double-blind randomized controlled trial that adding eplerenone to background medical therapy was cardioprotective in this population. The objective of this study was to evaluate the safety and efficacy of longer-term eplerenone therapy in boys with DMD. Results Eleven subjects (phase 1 baseline median [range] age: 13 [7 – 25] years from the original 12-month trial at a single participating center were enrolled. Importantly, those who entered the extension study who had been on eplerenone previously were significantly older than those who had originally been on placebo (median age 10.5 vs. 18.0 years, p = 0.045. During an additional 24-month open-label extension study, all boys received eplerenone 25 mg orally once daily to treat preclinical DMD cardiomyopathy, defined as evident myocardial damage by late gadolinium enhancement cardiac magnetic resonance (LGE with preserved ejection fraction (EF. The threshold for potassium level, the primary safety measure, was not exceeded in any non-hemolyzed blood sample. Over 24 months, left ventricular (LV systolic strain, a more sensitive marker whose more negative values indicate greater contractility significantly improved (median change -4.4%, IQR -5.8 to -0.9% in younger subjects whereas older subjects’ strain remained stable without significant worsening or improvement (median change 0.2%, IQR -1.1 to 4.3%. EF and extent of myocardial damage by LGE remained stable in both groups over 2 years. Conclusions Eplerenone offers effective and safe cardioprotection for boys with DMD, particularly when started at a younger age. Eplerenone is a useful clinical therapeutic option, particularly if treatment is initiated earlier in life when cardiac damage is minimal. Trial registration http://ClinicalTrials.gov identifier NCT01521546

Labeled factor IX kinetics in patients with hemophilia-B

International Nuclear Information System (INIS)

Smith, K.J.; Thompson, A.R.

1981-01-01

Labeled factor IX was infused five time into four patients with hemophilia-B. Ten-minute plasma recovery average 35% (SD +/- 2) and the mean T 1/2 beta-phase elimination was 23 hr (+/- 5). No alteration in the postinfusion 125I-factor-IX could be detected by radioautography of plasma samples run on polyacrylamide gels or on crossed-immunoelectrophoresis. Label was excreted into the urine as free 125I-iodide. Kinetics were similar when the labeled preparation was infused alone or with a commercial concentrate containing unlabeled factor IX. Infusion of factor IX in man is best described by a two-compartment open pharmacokinetic model where factor IX is distributed in a space larger than the plasma volume

LAMMPS Project Report for the Trinity KNL Open Science Period.

Energy Technology Data Exchange (ETDEWEB)

Moore, Stan Gerald [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Thompson, Aidan P. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wood, Mitchell [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-08-01

LAMMPS is a classical molecular dynamics code (lammps.sandia.gov) used to model materials science problems at Sandia National Laboratories and around the world. LAMMPS was one of three Sandia codes selected to participate in the Trinity KNL (TR2) Open Science period. During this period, three different problems of interest were investigated using LAMMPS. The first was benchmarking KNL performance using different force field models. The second was simulating void collapse in shocked HNS energetic material using an all-atom model. The third was simulating shock propagation through poly-crystalline RDX energetic material using a coarse-grain model, the results of which were used in an ACM Gordon Bell Prize submission. This report describes the results of these simulations, lessons learned, and some hardware issues found on Trinity KNL as part of this work.

Calendar Year 2008 Program Benefits for ENERGY STAR Labeled Products

Energy Technology Data Exchange (ETDEWEB)

Homan, GregoryK; Sanchez, Marla; Brown, RichardE; Lai, Judy

2010-08-24

This paper presents current and projected savings for ENERGY STAR labeled products, and details the status of the model as implemented in the September 2009 spreadsheets. ENERGY STAR is a voluntary energy efficiency labeling program operated jointly by the Environmental Protection Agency (US EPA) and the U.S. Department of Energy (US DOE), designed to identify and promote energy-efficient products, buildings and practices. Since the program inception in 1992, ENERGY STAR has become a leading international brand for energy efficient products, and currently labels more than thirty products, spanning office equipment, heating, cooling and ventilation equipment, commercial and residential lighting, home electronics, and major appliances. ENERGY STAR's central role in the development of regional, national and international energy programs necessitates an open process whereby its program achievements to date as well as projected future savings are shared with stakeholders. This report presents savings estimates for ENERGY STAR labeled products. We present estimates of energy, dollar, and carbon savings achieved by the program in the year 2008, annual forecasts for 2009 and 2010, and cumulative savings estimates for the period 1993 through 2008 and cumulative forecasts for the period 2009 through 2015. Through 2008 the program saved 8.8 Quads of primary energy and avoided the equivalent of 158 metric tones carbon (MtC). The forecast for the period 2009-2015 is 18.1 Quads or primary energy saved and 316 MtC emissions avoided. The sensitivity analysis bounds the best estimate of carbon avoided between 104 MtC and 213 MtC (1993 to 2008) and between 206 MtC and 444 MtC (2009 to 2015). In this report we address the following questions for ENERGY STAR labeled products: (1) How are ENERGY STAR impacts quantified; (2) What are the ENERGY STAR achievements; and (3) What are the limitations to our method?

Antihyperalgesic efficacy of 5% lidocaine medicated plaster in capsaicin and sunburn pain models--two randomized, double-blinded, placebo-controlled crossover trials in healthy volunteers.

Science.gov (United States)

Gustorff, Burkhard; Hauer, David; Thaler, Johannes; Seis, Astrid; Draxler, Julia

2011-12-01

The aim of this research is to analyze analgesic efficacy of the 5% lidocaine medicated plaster in two randomized, double-blinded, placebo-controlled, crossover studies in 16 healthy volunteers using capsaicin and sunburn pain models. Lidocaine and placebo plasters were simultaneously applied to forearms and thighs at contralateral body sites for three alternating 12-h plaster-on/plaster-off periods. Between the second and third plaster-on period, 4.2-cm circular spots on both pretreated thighs were irradiated with three times the individual minimal erythema dose of UVB light. After the last plaster-on period, 20 μl of 0.1% capsaicin was injected intradermally into both forearms. The study was repeated using a single 12-h plaster application. The area of pinprick hyperalgesia was diminished by 53% (p sunburn model; the intensity of mechanical hyperalgesia to rigid filaments (8 - 512 mN) was reduced in both models. Cold pain perception threshold was reduced (19.7°C ± 8.0 vs 21.8°C ± 6.8 for placebo, p sunburn). Similar effects were observed in the 12-h exposure study. No effect was seen on capsaicin-induced spontaneous pain and flare size, or blood flow in the sunburn area, and heat hyperalgesia in either study. Lidocaine plaster effectively treats mechanical hyperalgesia and cold pain.

Iron-59 absorption from soy hulls: intrinsic vs extrinsic labeling

International Nuclear Information System (INIS)

Lykken, G.I.; Mahalko, J.R.; Nielsen, E.J.; Dintzis, F.R.

1986-01-01

As part of an evaluation of the validity of the extrinsic labeling technique for measuring iron absorption, absorption from soy hulls extrinsically labeled ( 59 Fe added to bread dough) was compared with that from soy hulls intrinsically labeled ( 59 Fe incorporated into the soy plant during growth). Century soybeans were grown in a greenhouse. After pods had formed and were filling, each plant was stem injected twice, at 3 day intervals, with 22 μCi 59 Fe as FeCl 2 in 25 μl of 0.5 M HCl solution. After the plants had senesced, the soybeans were harvested, dried, shelled and the hulls removed. Standard meals containing 3.5 mg Fe/meal and up to 0.06 μCi 59 Fe in a soy hull bun were fed on 2 consecutive days to free-living volunteers in a crossover design. Absorption of 59 Fe was greater from intrinsically labeled soy hulls than from extrinsically labeled soy hulls, 20 +/- 20% vs 15 +/- 11% (n=14, p > 0.05 by paired t-test). Apparent absorption ranged from 1.3% to 77% from intrinsically labeled soy hulls and .5% to 29% from extrinsically labeled soy hulls with the highest absorption occurring in persons with low serum ferritin (S.F. < 8 ng/ml). These findings provide additional evidence that the extrinsic labeling method is a valid measure of iron bioavailability to humans

Crossover from quantum tunneling to classical hopping of domain walls in ferromagnets

Science.gov (United States)

Zhou, Bin; Liang, Jiu-Qing; Pu, Fu-Cho

2001-09-01

In the model of quantum tunneling of domain walls in ferromagnets given by Chudnovsky et al., the crossover from quantum tunneling to classical hopping is investigated. Considering the periodical boundary condition of spatial coordinate, the type of transition depends critically on the length of ferromagnet along the Y-axis.

Probiotics in diverticular disease of the colon: an open label study.

Science.gov (United States)

Lamiki, Pepu; Tsuchiya, Junji; Pathak, Surajit; Okura, Ruichi; Solimene, Umberto; Jain, Shalini; Kawakita, Shichiro; Marotta, Francesco

2010-03-01

To investigate the effectiveness and safety of a symbiotic mixture in preventing recurrence of constipation-related abdominal pain in patients with uncomplicated diverticular disease of the colon. Forty-six consecutive patients (10 men, 36 women, mean age 62.5 years, range 49 to 77 years), previously affected by symptomatic uncomplicated diverticular disease of the colon, were enrolled in a 6-month follow-up study in a prospective, randomized, open-label study. The following symptoms were assessed at entry and through follow-up by using a quantitative scale: constipation, diarrhoea and abdominal pain. After recruitment, the patients were assigned to the following treatment: SCM-III symbiotic mixture, 10 ml three times a day. The colonization of ingested Lactobacillus acidophilus 145 and Bifidobacterium spp. 420 was assessed by species-specific PCR. Forty-five patients completed the study (97%). Thirty-one patients (68%) were still symptom free after the 6th month of treatment. Treatment with SCM-III was regarded as "effective" or "very effective" in more than 78% of the patients altogether (pdiverticular disease of the colon, especially in those patients with constipation-predominant features.

Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: Results from a multicenter, open-label trial.

Science.gov (United States)

Vossler, David G; Wechsler, Robert T; Williams, Paulette; Byrnes, William; Therriault, Sheila

2016-10-01

To assess long-term use and safety of lacosamide (LCM) ≤800 mg/day monotherapy in patients with partial-onset seizures (POS) enrolled previously in a historical-controlled, conversion-to-monotherapy study (SP902; NCT00520741). Patients completing or exiting SP902 with LCM as monotherapy or as adjunctive therapy were eligible to enter this 2-year open-label extension (OLE) trial (SP904; NCT00530855) at a starting dose ±100 mg/day of their final SP902 dose. Investigators could adjust the LCM dose to 100-800 mg/day and add up to two antiepileptic drugs to optimize tolerability and seizure reduction. Three hundred twenty-two patients received LCM: 210 patients (65.2%) completed and 112 (34.8%) discontinued, most commonly owing to withdrawal of consent (9.3%). Two hundred fifty-eight patients (80.1%) had ≥1 year of and 216 (67.1%) had ≥2 years of LCM exposure, of whom 179/258 (69.4%) achieved LCM monotherapy lasting for any 12-month period, and 126/216 (58.3%) patients exposed for ≥24 months achieved LCM monotherapy for any 24-month period. Total exposure = 525.5 patient-years. The median modal dose was 500 mg/day. Two hundred ninety-two patients (90.7%) achieved LCM monotherapy at some point during the study. Sixty-five of 87 patients who exited and 193/235 who completed SP902 were exposed for ≥12 months, and 43.1% and 78.2%, respectively, achieved LCM monotherapy for ≥12 months. Median LCM monotherapy duration was 587.0 days (2-791 days); 91.0% of patients reported treatment-emergent adverse events, of which the most common were dizziness (27.3%), headache (17.1%), and nausea (14.3%). Compared with the SP902 study baseline, 74.2% of patients had a ≥50% seizure reduction and 5.6% were seizure-free at 24 months. The majority of patients were receiving LCM monotherapy at 0, 12, and 24 months in this OLE. Lacosamide monotherapy (median dose of 500 mg/day) had a safety profile similar to that of adjunctive therapy studies. These results support the use of

Size dependent thermal hysteresis in spin crossover nanoparticles reflected within a Monte Carlo based Ising-like model

International Nuclear Information System (INIS)

Atitoaie, Alexandru; Tanasa, Radu; Enachescu, Cristian

2012-01-01

Spin crossover compounds are photo-magnetic bistable molecular magnets with two states in thermodynamic competition: the diamagnetic low-spin state and paramagnetic high-spin state. The thermal transition between the two states is often accompanied by a wide hysteresis, premise for possible application of these materials as recording media. In this paper we study the influence of the system's size on the thermal hysteresis loops using Monte Carlo simulations based on an Arrhenius dynamics applied for an Ising like model with long- and short-range interactions. We show that using appropriate boundary conditions it is possible to reproduce both the drop of hysteresis width with decreasing particle size, the hysteresis shift towards lower temperatures and the incomplete transition, as in the available experimental data. The case of larger systems composed by several sublattices is equally treated reproducing the shrinkage of the hysteresis loop's width experimentally observed. - Highlights: ► A study concerning size effects in spin crossover nanoparticles hysteresis is presented. ► An Ising like model with short- and long-range interactions and Arrhenius dynamics is employed. ► In open boundary system the hysteresis width decreases with particle size. ► With appropriate environment, hysteresis loop is shifted towards lower temperature and transition is incomplete.

Use of Vitex agnus-castus in migrainous women with premenstrual syndrome: an open-label clinical observation.

Science.gov (United States)

Ambrosini, Anna; Di Lorenzo, Cherubino; Coppola, Gianluca; Pierelli, Francesco

2013-03-01

Premenstrual syndrome (PMS) affects most women during their reproductive life. Headache is regarded as a typical symptom of PMS and, close to menses, migrainous women could experience their worst migraine attacks. Vitex agnus-castus (VAC) is a phytopharmaceutical compound, considered worldwide to be a valid tool to treat PMS. Aim of this study is to explore if headache is ameliorate in migrainous women treated with VAC for PMS by an open-label clinical observation. Migrainous women with PMS were enrolled in the study and advised to assume a treatment with VAC (40 mg/day) for PMS for a 3-month period. Effects both on PMS and headache were assessed. Out of 107 women, 100 completed the 3-month treatment for PMS. Out of them, 66 women reported a dramatic reduction of PMS symptoms, 26 a mild reduction, and 8 no effect. Concerning migraine, 42 % of patients experienced a reduction higher than 50 % in frequency of monthly attacks, and 57 % of patients experienced a reduction higher than 50 % in monthly days with headache. No patients reported remarkable side effects. Pending a placebo-controlled trial to confirm our results, we observed that the use of VAC in migrainous women affected by PMS resulted to be safe and well tolerated, and may positively influence the frequency and duration of migraine attacks.

Bidirectional Active Learning: A Two-Way Exploration Into Unlabeled and Labeled Data Set.

Science.gov (United States)

Zhang, Xiao-Yu; Wang, Shupeng; Yun, Xiaochun

2015-12-01

In practical machine learning applications, human instruction is indispensable for model construction. To utilize the precious labeling effort effectively, active learning queries the user with selective sampling in an interactive way. Traditional active learning techniques merely focus on the unlabeled data set under a unidirectional exploration framework and suffer from model deterioration in the presence of noise. To address this problem, this paper proposes a novel bidirectional active learning algorithm that explores into both unlabeled and labeled data sets simultaneously in a two-way process. For the acquisition of new knowledge, forward learning queries the most informative instances from unlabeled data set. For the introspection of learned knowledge, backward learning detects the most suspiciously unreliable instances within the labeled data set. Under the two-way exploration framework, the generalization ability of the learning model can be greatly improved, which is demonstrated by the encouraging experimental results.

Bioavailability of ibuprofen following oral administration of standard ibuprofen, sodium ibuprofen or ibuprofen acid incorporating poloxamer in healthy volunteers

OpenAIRE

Dewland, Peter M; Reader, Sandie; Berry, Phillip

2009-01-01

Background The aim of this study was to compare the pharmacokinetic properties of sodium ibuprofen and ibuprofen acid incorporating poloxamer with standard ibuprofen acid tablets. Methods Twenty-two healthy volunteers were enrolled into this randomised, single-dose, 3-way crossover, open-label, single-centre, pharmacokinetic study. After 14 hours' fasting, participants received a single dose of 2 × 200 mg ibuprofen acid tablets (standard ibuprofen), 2 × 256 mg ibuprofen sodium dihydrate table...

Two-phase opening of Andaman Sea: a new seismotectonic insight

Science.gov (United States)

Khan, P. K.; Chakraborty, Partha Pratim

2005-01-01

High-resolution reconstruction of Benioff zone depth-dip angle trajectory for Burma-Java subduction margin between 2° and 17°N Lat. reveals two major episodes of plate geometry change expressed as abrupt deviation in subduction angle. Estimation of effective rate of subduction in different time slices (and then length of subducted slab) allowed drawing of isochrones in Ma interval through these trajectories for the time period 5-12 Ma. With these isochrones, the deformation events on the subducting Indian plate are constrained in time as of 4-5 and 11 Ma old. This well-constrained time connotation offered scope for the correlation of slab deformation events with the well-established two-phase opening history of the Andaman Sea. While the 11 Ma event recorded from southern part of the study area is correlated with early stretching and rifting phase, the 4-5 Ma event is interpreted as major forcing behind the spreading phase of the Andaman Sea. Systematic spatio-temporal evaluation of Indian plate obliquity on the Andaman Sea evolution shows its definite control on the early rifting phase, initiated towards south near northwest Sumatra. The much young spreading phase recorded towards north of 7° Lat. is possibly the result of late Miocene-Pliocene trench retreat and follow-up transcurrent movement (along Sagaing and Sumatran fault system) with NW-SE pull-apart extension. Nonconformity between plate shape and subduction margin geometry is interpreted as the causative force behind Mid-Miocene intraplate extension and tearing. Enhanced stretching in the overriding plate consequently caused active forearc subsidence, recorded all along this plate margin. Initial phase of the Andaman Sea opening presumably remains concealed in this early-middle Miocene forearc subsidence history. The late Miocene-Pliocene pull-apart opening and spreading was possibly initiated near the western part of the Mergui-Sumatra region and propagated northward in subsequent period. A temporary

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study.

Science.gov (United States)

Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

2015-06-01

The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration "time t" was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients' adherence to the treatment and quality of life.

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

Directory of Open Access Journals (Sweden)

André Daher

2015-06-01

Full Text Available The recommended treatment for latent tuberculosis (TB infection in adults is a daily dose of isoniazid (INH 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.

Three-way, three-period, crossover bioequivalence study of single oral dose of three brands of 300 mg phenytoin sodium tablets marketed in India, on healthy Indian human volunteers.

Science.gov (United States)

Doshi, Maulik S; Naik, Anuja A; Mehta, Mohit R; Gogtay, Nithya J; Thatte, Urmila M; Menon, Mala D

2013-10-01

To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin™ as the reference. A randomized, assessor-blind, three-way crossover design study was carried out over a period of 6 months after approval from the Institutional Review Board (IRB). Twenty-two healthy male participants received a single oral 300 mg oral tablet of either of the formulations with a 2-week washout. Blood samples were collected predose and at regular intervals postdose. Plasma phenytoin levels were estimated by high-performance liquid chromatography. Calculation of Cmax, AUC0-t, and AUC0-∞ was done by the linear trapezoidal rule and 90-110% margin (90% confidence interval (CI)) was used to assess bioequivalence. Twenty volunteers completed the study. It was seen that the log-transformed values of Cmax, AUC0-t, and AUC0-∞ of the test formulations were not within the specified limits. Bioinequivalence of available phenytoin brands indicates that switching brands could lead to variations in blood concentrations and thus impact safety and efficacy. If a brand switch is done for any reason, stringent drug-level monitoring is advised.

Effect of quetiapine vs. placebo on response to two virtual public speaking exposures in individuals with social phobia.

Science.gov (United States)

Donahue, Christopher B; Kushner, Matt G; Thuras, Paul D; Murphy, Tom G; Van Demark, Joani B; Adson, David E

2009-04-01

Clinical practice and open-label studies suggest that quetiapine (an atypical anti-psychotic) might improve symptoms for individuals with social anxiety disorder (SAD). The purpose of this study was to provide a rigorous test of the acute impact of a single dose of quetiapine (25mg) on SAD symptoms. Individuals with SAD (N=20) were exposed to a 4-min virtual reality (VR) public speaking challenge after having received quetiapine or placebo (double-blind) 1h earlier. A parallel VR challenge occurred 1 week later using a counter-balanced cross-over (within subject) design for the medication-placebo order between the two sessions. There was no significant drug effect for quetiapine on the primary outcome measures. However, quetiapine was associated with significantly elevated heart rate and sleepiness compared with placebo. Study findings suggest that a single dose of 25mg quetiapine is not effective in alleviating SAD symptoms in individuals with fears of public speaking.

Prospective, randomized, open-label, blinded-endpoint (PROBE) designed trials yield the same results as double-blind, placebo-controlled trials with respect to ABPM measurements.

Science.gov (United States)

Smith, David H; Neutel, Joel M; Lacourcière, Yves; Kempthorne-Rawson, Joan

2003-07-01

This meta-analysis aimed to determine whether ambulatory blood pressure monitoring (ABPM) results from double-blind, placebo-controlled (DBPC) and prospective, randomized, open-label, blinded-endpoint (PROBE) hypertension trials are statistically comparable. Two DBPC and three PROBE parallel-group studies were selected from an angiotensin II receptor blocker clinical programme. These were fixed-dose studies involving similar mild to moderate hypertensive patient populations. All used SpaceLabs 90207 ABPM devices, and each comprised a 4-week placebo period and a 4-8-week treatment period. Data from patients receiving telmisartan 80 mg were used to compare the results of DBPC (126 patients) and PROBE (734 patients) trials. The analysis had approximately 87% power to show equivalence between the two design types in terms of ruling out differences of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. Office blood pressure was also compared. The change from baseline in mean 24-h ambulatory SBP was -12.2 mmHg in DBPC trials and -12.3 mmHg in PROBE trials, a rounded difference of 0.2 mmHg [95% confidence interval (CI): -1.8, 2.1]. The change from baseline in mean 24-h ambulatory DBP was -7.7 mmHg in DBPC trials versus -7.9 mmHg in PROBE trials, a difference of 0.2 mmHg (95% CI: -1.1, 1.5). Ambulatory pulse pressure results were identical. Thus, changes in mean 24-h ambulatory blood pressure from the DBPC and PROBE trials in this meta-analysis are statistically equivalent in terms of ruling out a difference of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. This supports the validity of the PROBE design in assessing antihypertensive efficacy based on blinded ABPM measurements.

Effect of comorbid tics on a clinically meaningful response to 8-week open-label trial of fluoxetine in obsessive compulsive disorder.

Science.gov (United States)

Husted, David S; Shapira, Nathan A; Murphy, Tanya K; Mann, Giselle D; Ward, Herbert E; Goodman, Wayne K

2007-01-01

Currently, there are limited published data evaluating the effects of tics on serotonin reuptake inhibitor (SRI) monotherapy responses in treating obsessive-compulsive disorder (OCD). One retrospective case-controlled analysis of OCD patients treated with SRI monotherapy showed lesser improvement in OCD symptoms in patients with tics than those without. However, more recently there were preliminary reports of OCD subjects treated with SRI monotherapy which did not demonstrate poorer response in subjects with tics or Tourette's Syndrome (TS). The specific aim of this study was to investigate whether the presence of comorbid chronic tics affected "clinically meaningful improvement" [McDougle, C.J., Goodman, W.K., Leckman, J.F., Barr, L.C., Heninger, G.R., Price, L.H., 1993. The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. Journal of Clinical Psychopharmacology 13, 354-358] of OCD in an 8-week open-label trial of fluoxetine monotherapy. Seventy-four adult subjects (13 patients with comorbid chronic tics and 61 patients without tics) with a primary DSM-IV OCD diagnosis were treated with up to 40mg fluoxetine for 8 weeks and had at least one post-baseline evaluation. The results indicate that there was a significant response by time in both fluoxetine-with-tic subjects and fluoxetine-without-tic subjects. Additionally, there were 3 (23.0%) OCD subjects with tics who had clinically meaningful improvement versus 16 (26.2%) OCD subjects without tics that demonstrated similar levels of improvement. These findings indicate that OCD patients with or without chronic tic disorders did not have a differential response to an 8-week open-label trial of fluoxetine. Limitations include the relatively low number of tic subjects and the open-label nature of the study. Additional data are needed on how comorbid tics may affect SRI treatment response in OCD.

Copper absorption from foods labelled intrinsically and extrinsically with Cu-65 stable isotope.

Science.gov (United States)

Harvey, L J; Dainty, J R; Beattie, J H; Majsak-Newman, G; Wharf, S G; Reid, M D; Fairweather-Tait, S J

2005-03-01

To determine copper absorption from copper containing foods labelled either intrinsically or extrinsically with a highly enriched Cu-65 stable isotope label. A longitudinal cross-over study. The study was conducted at the Institute of Food Research, Human Nutrition Unit, Norwich, UK. Subjects were recruited locally via advertisements placed around the Norwich Research Park. A total of 10 volunteers (nine female, one male) took part in the study, but not all volunteers completed each of the test meals. A highly enriched Cu-65 stable isotope label was administered to volunteers in the form of a reference dose or in breakfast test meals consisting of red wine, soya beans, mushrooms or sunflower seeds. Faecal monitoring and mass spectrometry techniques were used to estimate the relative quantities of copper absorbed from the different test meals. True copper absorption from the reference dose (54%) was similar to extrinsically labelled red wine (49%) and intrinsically labelled sunflower seeds (52%), but significantly higher than extrinsically labelled mushrooms (35%), intrinsically (29%) and extrinsically (15%) labelled soya beans and extrinsically labelled sunflower seed (32%) test meals. The use of Cu-65 extrinsic labels in copper absorption studies requires validation according to the food being examined; intrinsic and extrinsic labelling produced significantly different results for sunflower seeds.

[Preliminary results of an open-label observational study evaluating the efficacy and safety of Prolia used in women with postmenopausal osteoporosis].

Science.gov (United States)

Ershova, O B; Lesniak, O M; Belova, K Iu; Nazarova, A V; Manovitskaia, A V; Musaeva, T M; Musraev, R M; Nurlygaianov, R Z; Rozhinskaia, L Ia; Skripnikova, I A; Toroptsova, N V

2014-01-01

To evaluate the efficacy and safety of Denosumab (Prolia), a first-line osteoporosis (OP) medication that is a fully human monoclonal antibody to the receptor activator of nuclear factor xB ligand (RANKL), within an open-label observational study. Patients aged 50 years or older with postmenopausal OP, who were treated with Prolia in clinical practice, were examined. The concentrations of the bone resorption (BR) marker of C-terminal telopeptide and other laboratory indicators (total serum calcium, total alkaline phosphatase, and creatinine) were measured following 3 months. Adverse drug reactions were recorded. Three months after initiation of the investigation, there was a significant decrease in the BR marker C-terminal telopeptide (by 89%; p<0.0001). There were rare adverse reactions: hypocalcemia in 3 (5.9%) patients, arthralgias in 2 (3.9%), and eczema in 1 (1.9%). There were neither serious adverse events nor study withdrawal cases. The preliminary results of the open-label study of Prolia in postmenopausal OP suggest that the significantly lower BR activity determines the efficacy of this drug and its high safety.

High-level production of C-11-carboxyl-labeled amino acids

International Nuclear Information System (INIS)

Washburn, L.C.; Sun, T.T.; Byrd, B.L.; Hayes, R.L.; Butler, T.A.; Callahan, A.P.

1979-01-01

Carbon-11-labeled amino acids have significant potential as agents for positron tomographic functional imaging. We have developed a rapid, high-temperature, high-pressure modification of the Buecherer--Strecker amino acid synthesis and found it to be quite general for the production of C-11-carboxyl-labeled neutral amino acids. Production of C-11-carboxyl-labeled DL-tryptophan requires certain modifications in the procedure. Twelve different amino acids have been produced to date by this technique. Synthesis and chromatographic purification require approximately 40 min, and C-11-carboxyl-labeled amino acids have been produced in yields of up to 425 mCi. Two C-11-carboxyl-labeled amino acids are being investigated clinically for tumor scanning and two others for pancreatic imaging. Over 120 batches of the various agents have been produced for clinical use over a three-year period

Crossover between the Gaussian orthogonal ensemble, the Gaussian unitary ensemble, and Poissonian statistics.

Science.gov (United States)

Schweiner, Frank; Laturner, Jeanine; Main, Jörg; Wunner, Günter

2017-11-01

Until now only for specific crossovers between Poissonian statistics (P), the statistics of a Gaussian orthogonal ensemble (GOE), or the statistics of a Gaussian unitary ensemble (GUE) have analytical formulas for the level spacing distribution function been derived within random matrix theory. We investigate arbitrary crossovers in the triangle between all three statistics. To this aim we propose an according formula for the level spacing distribution function depending on two parameters. Comparing the behavior of our formula for the special cases of P→GUE, P→GOE, and GOE→GUE with the results from random matrix theory, we prove that these crossovers are described reasonably. Recent investigations by F. Schweiner et al. [Phys. Rev. E 95, 062205 (2017)2470-004510.1103/PhysRevE.95.062205] have shown that the Hamiltonian of magnetoexcitons in cubic semiconductors can exhibit all three statistics in dependence on the system parameters. Evaluating the numerical results for magnetoexcitons in dependence on the excitation energy and on a parameter connected with the cubic valence band structure and comparing the results with the formula proposed allows us to distinguish between regular and chaotic behavior as well as between existent or broken antiunitary symmetries. Increasing one of the two parameters, transitions between different crossovers, e.g., from the P→GOE to the P→GUE crossover, are observed and discussed.

Improving Genetic Algorithm with Fine-Tuned Crossover and Scaled Architecture

Directory of Open Access Journals (Sweden)

Ajay Shrestha

2016-01-01

Full Text Available Genetic Algorithm (GA is a metaheuristic used in solving combinatorial optimization problems. Inspired by evolutionary biology, GA uses selection, crossover, and mutation operators to efficiently traverse the solution search space. This paper proposes nature inspired fine-tuning to the crossover operator using the untapped idea of Mitochondrial DNA (mtDNA. mtDNA is a small subset of the overall DNA. It differentiates itself by inheriting entirely from the female, while the rest of the DNA is inherited equally from both parents. This unique characteristic of mtDNA can be an effective mechanism to identify members with similar genes and restrict crossover between them. It can reduce the rate of dilution of diversity and result in delayed convergence. In addition, we scale the well-known Island Model, where instances of GA are run independently and population members exchanged periodically, to a Continental Model. In this model, multiple web services are executed with each web service running an island model. We applied the concept of mtDNA in solving Traveling Salesman Problem and to train Neural Network for function approximation. Our implementation tests show that leveraging these new concepts of mtDNA and Continental Model results in relative improvement of the optimization quality of GA.

Does crossover innervation really affect the clinical outcome? A comparison of outcome between unilateral and bilateral digital nerve repair

Directory of Open Access Journals (Sweden)

Melike Oruç

2016-01-01

Full Text Available Digital nerve injuries are the mostly detected nerve injury in the upper extremity. However, since the clinical phenomenon of crossover innervation at some degree from uninjured digital nerve to the injured side occurs after digital nerve injuries is sustained, one could argue that this concept might even result in the overestimation of the outcome of the digital nerve repair. With this knowledge in mind, this study aimed to present novel, pure, focused and valuable clinical data by comparing the outcomes of bilateral and unilateral digital nerve repair. A retrospective review of 28 fingers with unilateral or bilateral digital nerve repair using end-to-end technique in 19 patients within 2 years was performed. Weber′s two-point discrimination, sharp/dull discrimination, warm/cold sensation and Visual Analog Scale scoring were measured at final 12-month follow ups in all patients. There was no significant difference in recovery of sensibility after unilateral and bilateral digital nerve repairs. Though there is crossover innervation microscopically, it is not important in the clinical evaluation period. According to clinical findings from this study, crossover innervations appear to be negligible in the estimation of outcomes of digital neurorrhaphy.

The BCS-BEC Crossover

Science.gov (United States)

Parish, Meera M.

2015-09-01

This chapter presents the crossover from the Bardeen-Cooper-Schrieffer (BCS) state of weakly correlated pairs of fermions to the Bose-Einstein condensation (BEC) of diatomic molecules in the atomic Fermi gas. Our aim is to provide a pedagogical review of the BCS-BEC crossover, with an emphasis on the basic concepts, particularly those that are not generally known or are difficult to find in the literature. We shall not attempt to give an exhaustive survey of current research in the limited space here; where possible, we will direct the reader to more extensive reviews.

Multi-label Learning with Missing Labels Using Mixed Dependency Graphs

KAUST Repository

Wu, Baoyuan

2018-04-06

This work focuses on the problem of multi-label learning with missing labels (MLML), which aims to label each test instance with multiple class labels given training instances that have an incomplete/partial set of these labels (i.e., some of their labels are missing). The key point to handle missing labels is propagating the label information from the provided labels to missing labels, through a dependency graph that each label of each instance is treated as a node. We build this graph by utilizing different types of label dependencies. Specifically, the instance-level similarity is served as undirected edges to connect the label nodes across different instances and the semantic label hierarchy is used as directed edges to connect different classes. This base graph is referred to as the mixed dependency graph, as it includes both undirected and directed edges. Furthermore, we present another two types of label dependencies to connect the label nodes across different classes. One is the class co-occurrence, which is also encoded as undirected edges. Combining with the above base graph, we obtain a new mixed graph, called mixed graph with co-occurrence (MG-CO). The other is the sparse and low rank decomposition of the whole label matrix, to embed high-order dependencies over all labels. Combining with the base graph, the new mixed graph is called as MG-SL (mixed graph with sparse and low rank decomposition). Based on MG-CO and MG-SL, we further propose two convex transductive formulations of the MLML problem, denoted as MLMG-CO and MLMG-SL respectively. In both formulations, the instance-level similarity is embedded through a quadratic smoothness term, while the semantic label hierarchy is used as a linear constraint. In MLMG-CO, the class co-occurrence is also formulated as a quadratic smoothness term, while the sparse and low rank decomposition is incorporated into MLMG-SL, through two additional matrices (one is assumed as sparse, and the other is assumed as low

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study.

Science.gov (United States)

Tahara, Shigeyuki; Murakami, Mami; Kaneko, Tomomi; Shimatsu, Akira

2017-07-28

A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levelsacromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GHacromegaly or pituitary gigantism.

Daily consumption of fermented soymilk helps to improve facial wrinkles in healthy postmenopausal women in a randomized, parallel-group, open-label trial

Directory of Open Access Journals (Sweden)

Mitsuyoshi Kano

2018-02-01

Full Text Available Background: Soymilk fermented by lactobacilli and/or bifidobacteria is attracting attention due to the excellent bioavailability of its isoflavones. We investigated the effects of fermented soymilk containing high amounts of isoflavone aglycones on facial wrinkles and urinary isoflavones in postmenopausal women in a randomized, parallel-group, open-label trial. Healthy Japanese women were randomly divided into active (n = 44, mean age 56.3 ± 0.5 or control (n = 44, mean age 56.1 ± 0.5 groups, who consumed or did not consume a bottle of soymilk fermented by Bifidobacterium breve strain Yakult and Lactobacillus mali for 8 weeks. Maximum depth of wrinkles around the crow’s feet area and other wrinkle parameters were evaluated as primary and secondary endpoints respectively at weeks 0, 4, and 8 during the consumption period. Urinary isoflavone levels were determined by liquid chromatography-mass spectrometry. Results: The active group demonstrated significant improvements in the maximum depth (p=0.015 and average depth (p=0.04 of wrinkles, and significantly elevated urinary isoflavones (daidzein, genistein, and glycitein; each p < 0.001 compared with the control during the consumption period. No serious adverse effects were recorded. Conclusion: These findings suggest that fermented soymilk taken daily may improve facial wrinkles and elevate urinary isoflavones in healthy postmenopausal women.

Calendar Year 2009 Program Benefits for ENERGY STAR Labeled Products

Energy Technology Data Exchange (ETDEWEB)

Homan, Gregory K; Sanchez, Marla C.; Brown, Richard E.

2010-11-15

ENERGY STAR is a voluntary energy efficiency labeling program operated jointly by the Environmental Protection Agency (US EPA) and the U.S. Department of Energy (US DOE), designed to identify and promote energy-efficient products, buildings and practices. Since the program inception in 1992, ENERGY STAR has become a leading international brand for energy efficient products, and currently labels more than thirty products, spanning office equipment, heating, cooling and ventilation equipment, commercial and residential lighting, home electronics, and major appliances. ENERGY STAR's central role in the development of regional, national and international energy programs necessitates an open process whereby its program achievements to date as well as projected future savings are shared with stakeholders. This report presents savings estimates from the use ENERGY STAR labeled products. We present estimates of energy, dollar, and carbon savings achieved by the program in the year 2009, annual forecasts for 2010 and 2011, and cumulative savings estimates for the period 1993 through 2009 and cumulative forecasts for the period 2010 through 2015. Through 2009 the program saved 9.5 Quads of primary energy and avoided the equivalent of 170 million metric tons carbon (MMTC). The forecast for the period 2009-2015 is 11.5 Quads or primary energy saved and 202 MMTC emissions avoided. The sensitivity analysis bounds the best estimate of carbon avoided between 110 MMTC and 231 MMTC (1993 to 2009) and between 130 MMTC and 285 MMTC (2010 to 2015).

Esophageal transit and in vivo disintegration of branded risedronate sodium tablets and two generic formulations of alendronic acid tablets: a single-center, single-blind, six-period crossover study in healthy female subjects.

Science.gov (United States)

Perkins, Alan C; Blackshaw, P Elaine; Hay, Peter D; Lawes, Simon C; Atherton, Clare T; Dansereau, Richard J; Wagner, Leigh K; Schnell, Dan J; Spiller, Robin C

2008-05-01

Delayed esophageal transit or disintegration of oral bisphosphonate tablets before they enter the stomach may be of concern with respect to iatrogenic complications among patients receiving longterm treatment. Different formulations of generic bisphosphonate tablets meeting regulatory requirements may have substantial differences in pharmaceutical attributes from the branded product that may result in different characteristics during esophageal transit. The primary objective of this study was to evaluate and compare esophageal transit times and in vivo disintegration of 3 bisphosphonate formulations, one branded and the others generic, that are commercially available in Canada and the United Kingdom. This was a single-center, randomized, singleblind, 6-period crossover study in healthy postmenopausal women aged >50 years. Each subject received a single oral dose of a branded risedronate sodium 35-mg tablet and 2 generic formulations of alendronic acid 70-mg tablets (Novopharm Limited, Toronto, Canada, and Teva UK Limited, Morley, United Kingdom) in both the erect and semisupine (45 degrees ) positions. Although the products are labeled to be taken in the erect position, the semisupine position was included to simulate dosing in bedridden patients. Subjects took tablets with 30 mL of water in the morning after an overnight fast. The tablets were radiolabeled with technetium-99m ion-exchange resins to enable visualization and measurement of esophageal transit time and disintegration using a gamma camera. Dynamic scintigraphic images were obtained for a total of 10 minutes: 2 images per second for the first 30 seconds and 1 image every 15 seconds for 9.5 minutes. This was a mechanistic study and tolerability was not assessed. The study was conducted in 20 healthy white female subjects with a mean age of 62 years (range, 51-77 years). The effect of body position was statistically significant (P = 0.043), with the estimated hazard ratio (HR) of 0.74 indicating longer

Intercomparison of open-path trace gas measurements with two dual-frequency-comb spectrometers

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E. M. Waxman

2017-09-01

Full Text Available We present the first quantitative intercomparison between two open-path dual-comb spectroscopy (DCS instruments which were operated across adjacent 2 km open-air paths over a 2-week period. We used DCS to measure the atmospheric absorption spectrum in the near infrared from 6023 to 6376 cm−1 (1568 to 1660 nm, corresponding to a 355 cm−1 bandwidth, at 0.0067 cm−1 sample spacing. The measured absorption spectra agree with each other to within 5 × 10−4 in absorbance without any external calibration of either instrument. The absorption spectra are fit to retrieve path-integrated concentrations for carbon dioxide (CO2, methane (CH4, water (H2O, and deuterated water (HDO. The retrieved dry mole fractions agree to 0.14 % (0.57 ppm for CO2, 0.35 % (7 ppb for CH4, and 0.40 % (36 ppm for H2O at  ∼  30 s integration time over the 2-week measurement campaign, which included 24 °C outdoor temperature variations and periods of strong atmospheric turbulence. This agreement is at least an order of magnitude better than conventional active-source open-path instrument intercomparisons and is particularly relevant to future regional flux measurements as it allows accurate comparisons of open-path DCS data across locations and time. We additionally compare the open-path DCS retrievals to a World Meteorological Organization (WMO-calibrated cavity ring-down point sensor located along the path with good agreement. Short-term and long-term differences between the open-path DCS and point sensor are attributed, respectively, to spatial sampling discrepancies and to inaccuracies in the current spectral database used to fit the DCS data. Finally, the 2-week measurement campaign yields diurnal cycles of CO2 and CH4 that are consistent with the presence of local sources of CO2 and absence of local sources of CH4.

Relativistic BCS-BEC crossover at finite temperature and its application to color superconductivity

International Nuclear Information System (INIS)

He Lianyi; Zhuang Pengfei

2007-01-01

The nonrelativistic G 0 G formalism of BCS-BEC crossover at finite temperature is extended to relativistic fermion systems. The uncondensed pairs contribute a pseudogap to the fermion excitations. The theory recovers the BCS mean field approximation at zero temperature and the nonrelativistic results in a proper limit. For massive fermions, when the coupling strength increases, there exist two crossovers from the weak coupling BCS superfluid to the nonrelativistic BEC state and then to the relativistic BEC state. For color superconductivity at moderate baryon density, the matter is in the BCS-BEC crossover region, and the behavior of the pseudogap is quite similar to that found in high temperature superconductors

Numerical simulation of a device with two spin crossover complexes: application for temperature and pressure sensors

Science.gov (United States)

Linares, Jorge; Eddine Allal, Salah; Dahoo, Pierre Richard; Garcia, Yann

2017-12-01

The spin-crossover (SCO) phenomenon is related to the ability of a transition metal to change its spin state vs. a given perturbation. For an iron(II) SCO complexes the reversible changes involve the diamagnetic low-spin (S = 0) and the paramagnetic high-spin (HS S = 2) states [1,2,3]. In this contribution we simulate the HS Fraction (nHS) for different set values of temperature and pressure for a device using two SCO complexes with weak elastic interactions. We improve the calculation given by Linares et al. [4], taking also into account different volume (VHS, VLS) changes of the SCO. We perform all the calculation in the frame work of an Ising-like model solved in the mean-field approximation. The two SCO show in the case of “weak elastic interactions”, gradual spin transitions such that both temperature and pressure values can be obtained from the optical observation in the light of calculations discussed in this article.

Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study

Directory of Open Access Journals (Sweden)

Jenkins TM

2012-07-01

Full Text Available Tim M Jenkins, Trevor S Smart, Frances Hackman, Carol Cooke, Keith KC TanClinical Research, Pfizer Worldwide Research and Development, Sandwich, Kent, UKBackground: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population.Methods: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study.Results: Twenty-five adults (20–70 years of age with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1 pregabalin followed by placebo or (2 placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5–15. In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint were significantly reduced for pregabalin versus placebo, with a mean treatment difference of -0.81 (95% confidence interval: -1.45 to -0.17; P = 0.015.Conclusion: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain.Keywords: pregabalin, post-traumatic peripheral neuropathic pain, randomized

Two major open days this spring

CERN Document Server

2008-01-01

CERN will be organising two Open Days in April 2008, one for CERN employees and their families from 9 a.m. to 3 p.m. on Saturday, 5 April, and another for the general public from 9 a.m. to 7 p.m. on Sunday, 6 April.

The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study.

Science.gov (United States)

Chasset, François; Arnaud, Laurent; Costedoat-Chalumeau, Nathalie; Zahr, Noel; Bessis, Didier; Francès, Camille

2016-04-01

Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE. We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders. The main limitations of the study are its open-label design and the limited number of patients included. Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A comparison of two methods of labelling autologous platelets with 111In-oxine in five different species

International Nuclear Information System (INIS)

Christenson, J.T.; Arvidsson, D.; Thoerne, J.; Norgren, L.; Olsson, P.I.; Strand, S.E.

1983-01-01

Several different methods for labelling autologous platelets with 111 In-oxine have been described. However, no comparative study has been reported. In the present investigation two different labelling methods were compared in terms of labelling efficiency and platelet function in five species: human, dog, pig, rabbit and rat. One of the labelling methods, utilising among other things a serum albumin gradient separation fo platelets and incubation of 111 In-oxine in a water bath at 37 0 C, was superior in all species with significantly higher labelling efficiency and unchanged platelet function. (orig.)

An Analysis of Patient Adherence to Treatment during a 1-Year, Open-Label Study of OROS[R] Methylphenidate in Children with ADHD

Science.gov (United States)

Faraone, Stephen V.; Biederman, Joseph; Zimmerman, Brenda

2007-01-01

Objective: Treatment adherence is an important aspect of ADHD symptom management, but there are many factors that may influence adherence. Method: This analysis assessed adherence to OROS methylphenidate during a 1-year, open-label study in children. Adherence was defined as the number of days medication was taken divided by the number of days in…

Hyperon puzzle, hadron-quark crossover and massive neutron stars

Energy Technology Data Exchange (ETDEWEB)

Masuda, Kota [The University of Tokyo, Department of Physics, Tokyo (Japan); Nishina Center, RIKEN, Theoretical Research Division, Wako (Japan); Hatsuda, Tetsuo [Nishina Center, RIKEN, Theoretical Research Division, Wako (Japan); The University of Tokyo, Kavli IPMU (WPI), Chiba (Japan); Takatsuka, Tatsuyuki [Nishina Center, RIKEN, Theoretical Research Division, Wako (Japan)

2016-03-15

Bulk properties of cold and hot neutron stars are studied on the basis of the hadron-quark crossover picture where a smooth transition from the hadronic phase to the quark phase takes place at finite baryon density. By using a phenomenological equation of state (EOS) ''CRover'', which interpolates the two phases at around 3 times the nuclear matter density (ρ{sub 0}), it is found that the cold NSs with the gravitational mass larger than 2M {sub CircleDot} can be sustained. This is in sharp contrast to the case of the first-order hadron-quark transition. The radii of the cold NSs with the CRover EOS are in the narrow range (12.5 ± 0.5) km which is insensitive to the NS masses. Due to the stiffening of the EOS induced by the hadron-quark crossover, the central density of the NSs is at most 4 ρ{sub 0} and the hyperon-mixing barely occurs inside the NS core. This constitutes a solution of the long-standing hyperon puzzle. The effect of color superconductivity (CSC) on the NS structures is also examined with the hadron-quark crossover. For the typical strength of the diquark attraction, a slight softening of the EOS due to two-flavor CSC (2SC) takes place and the maximum mass is reduced by about 0.2M {sub CircleDot}. The CRover EOS is generalized to the supernova matter at finite temperature to describe the hot NSs at birth. The hadron-quark crossover is found to decrease the central temperature of the hot NSs under isentropic condition. The gravitational energy release and the spin-up rate during the contraction from the hot NS to the cold NS are also estimated. (orig.)

Hyperon puzzle, hadron-quark crossover and massive neutron stars

International Nuclear Information System (INIS)

Masuda, Kota; Hatsuda, Tetsuo; Takatsuka, Tatsuyuki

2016-01-01

Bulk properties of cold and hot neutron stars are studied on the basis of the hadron-quark crossover picture where a smooth transition from the hadronic phase to the quark phase takes place at finite baryon density. By using a phenomenological equation of state (EOS) ''CRover'', which interpolates the two phases at around 3 times the nuclear matter density (ρ 0 ), it is found that the cold NSs with the gravitational mass larger than 2M CircleDot can be sustained. This is in sharp contrast to the case of the first-order hadron-quark transition. The radii of the cold NSs with the CRover EOS are in the narrow range (12.5 ± 0.5) km which is insensitive to the NS masses. Due to the stiffening of the EOS induced by the hadron-quark crossover, the central density of the NSs is at most 4 ρ 0 and the hyperon-mixing barely occurs inside the NS core. This constitutes a solution of the long-standing hyperon puzzle. The effect of color superconductivity (CSC) on the NS structures is also examined with the hadron-quark crossover. For the typical strength of the diquark attraction, a slight softening of the EOS due to two-flavor CSC (2SC) takes place and the maximum mass is reduced by about 0.2M CircleDot . The CRover EOS is generalized to the supernova matter at finite temperature to describe the hot NSs at birth. The hadron-quark crossover is found to decrease the central temperature of the hot NSs under isentropic condition. The gravitational energy release and the spin-up rate during the contraction from the hot NS to the cold NS are also estimated. (orig.)

Within-Subject Mediation Analysis in AB/BA Crossover Designs.

Science.gov (United States)

Josephy, Haeike; Vansteelandt, Stijn; Vanderhasselt, Marie-Anne; Loeys, Tom

2015-05-01

Crossover trials are widely used to assess the effect of a reversible exposure on an outcome of interest. To gain further insight into the underlying mechanisms of this effect, researchers may be interested in exploring whether or not it runs through a specific intermediate variable: the mediator. Mediation analysis in crossover designs has received scant attention so far and is mostly confined to the traditional Baron and Kenny approach. We aim to tackle mediation analysis within the counterfactual framework and elucidate the assumptions under which the direct and indirect effects can be identified in AB/BA crossover studies. Notably, we show that both effects are identifiable in certain statistical models, even in the presence of unmeasured time-independent (or upper-level) confounding of the mediator-outcome relation. Employing the mediation formula, we derive expressions for the direct and indirect effects in within-subject designs for continuous outcomes that lend themselves to linear modelling, under a large variety of settings. We discuss an estimation approach based on regressing differences in outcomes on differences in mediators and show how to allow for period effects as well as different types of moderation. The performance of this approach is compared to other existing methods through simulations and is illustrated with data from a neurobehavioural study. Lastly, we demonstrate how a sensitivity analysis can be performed that is able to assess the robustness of both the direct and indirect effect against violation of the "no unmeasured lower-level mediator-outcome confounding" assumption.

The usefulness of two-port video-assisted thoracosopic surgery in low-risk patients with secondary spontaneous pneumothorax compared with open thoracotomy

Directory of Open Access Journals (Sweden)

Kyoung Taek Park

2014-01-01

Conclusion: In selected patients with secondary spontaneous pneumothorax treated with surgical approach, two-port VATS resulted in shorter postoperative drainage period and hospital stay compared with open thoracotomy.

Two new French quality labels

Energy Technology Data Exchange (ETDEWEB)

Bresler, Ines

2012-07-01

'Origine France Garantie' and 'AQPV' are the new product labels that were presented in France in 2011. While the first is aimed at the entire industry, the latter is an effort to strengthen the PV industry. By raising the enthusiasm for local products, the French government hopes to keep the flood of foreign imports at bay. (orig.)

Hysteretic behavior of spin-crossover noise driven system

Energy Technology Data Exchange (ETDEWEB)

Gudyma, Iurii [Department of General Physics, Chernivtsi National University, Chernivtsi 58012 (Ukraine); Maksymov, Artur, E-mail: maxyartur@gmail.com [Department of General Physics, Chernivtsi National University, Chernivtsi 58012 (Ukraine); Advanced Materials Research Institute, University of New Orleans, LA 70148 (United States); Dimian, Mihai [Department of Electrical and Computer Engineering, Howard University, Washington DC, 20059 (United States); Faculty of Electrical Engineering and Computer Science, Stefan cel Mare University, Suceava 720229 (Romania)

2016-04-01

The influence of white Gaussian noise on hysteretic behavior of spin-crossover system is analyzed in the framework of stochastic Langevin dynamics. Various stochastic simulations are performed and several important properties of spin-transition in spin-crossover system driven by noise are reproduced. The numerical results are tested against the stationary probability function and the associated dynamic potential obtained from Fokker–Planck equation corresponding to spin-crossover Langevin dynamics. The dependence of light-induced optical hysteresis width and non-hysteretic transition curve slope on the noise intensity is illustrated. The role of low-spin and high-spin phase stabilities in the hysteretic behavior of noise-driven spin-crossover system is discussed.

LFQProfiler and RNP(xl): Open-Source Tools for Label-Free Quantification and Protein-RNA Cross-Linking Integrated into Proteome Discoverer.

Science.gov (United States)

Veit, Johannes; Sachsenberg, Timo; Chernev, Aleksandar; Aicheler, Fabian; Urlaub, Henning; Kohlbacher, Oliver

2016-09-02

Modern mass spectrometry setups used in today's proteomics studies generate vast amounts of raw data, calling for highly efficient data processing and analysis tools. Software for analyzing these data is either monolithic (easy to use, but sometimes too rigid) or workflow-driven (easy to customize, but sometimes complex). Thermo Proteome Discoverer (PD) is a powerful software for workflow-driven data analysis in proteomics which, in our eyes, achieves a good trade-off between flexibility and usability. Here, we present two open-source plugins for PD providing additional functionality: LFQProfiler for label-free quantification of peptides and proteins, and RNP(xl) for UV-induced peptide-RNA cross-linking data analysis. LFQProfiler interacts with existing PD nodes for peptide identification and validation and takes care of the entire quantitative part of the workflow. We show that it performs at least on par with other state-of-the-art software solutions for label-free quantification in a recently published benchmark ( Ramus, C.; J. Proteomics 2016 , 132 , 51 - 62 ). The second workflow, RNP(xl), represents the first software solution to date for identification of peptide-RNA cross-links including automatic localization of the cross-links at amino acid resolution and localization scoring. It comes with a customized integrated cross-link fragment spectrum viewer for convenient manual inspection and validation of the results.

Brimonidine 0.2% given two or three times daily versus timolol maleate 0.5% in primary open-angle glaucoma.

Science.gov (United States)

Konstas, A G; Stewart, W C; Topouzis, F; Tersis, I; Holmes, K T; Stangos, N T

2001-06-01

To evaluate the efficacy and safety of brimonidine 0.2% two or three times daily versus timolol maleate 0.5% solution twice daily. Patients with primary open-angle glaucoma were randomized by Latin square technique to one of the three treatment sequences in this crossover, prospective double-masked trial. Each treatment period consisted of 6 weeks of chronic dosing followed by a diurnal curve for the intraocular pressure measured at 08:00, 10:00, 16:00, 18:00, 20:00, 22:00, and 24:00 hours. Intraocular pressure was measured by applanation tonometry. Thirty patients completed this trial. The average diurnal intraocular pressures in the trial were measured for timolol maleate (17.7 +/- 2.7 mm Hg), brimonidine given three times daily (18.0 +/- 2.2 mm Hg), and brimonidine given twice daily (19.2 +/- 2.4 mm Hg). There was a statistical difference between groups (P <.005). When groups were compared by pairs, three times daily dosing with brimonidine and timolol maleate both reduced the pressure more than twice daily brimonidine at every time point past 10:00 hours and for the diurnal curve (P <.05). In contrast, three times daily brimonidine and timolol maleate were statistically similar for the diurnal pressure, and each time point, except timolol maleate, decreased the pressure more at 16:00 (P =.042). Safety was similar between groups. This study demonstrated that both timolol maleate twice daily and brimonidine three times daily provide a similar intraocular pressure reduction to each other. Timolol maleate twice daily and brimonidine three times daily provide a greater decrease in pressure in the late afternoon and nighttime hours, compared with brimonidine twice daily.

Energy momentum tensor and marginal deformations in open string field theory

International Nuclear Information System (INIS)

Sen, Ashoke

2004-01-01

Marginal boundary deformations in a two dimensional conformal field theory correspond to a family of classical solutions of the equations of motion of open string field theory. In this paper we develop a systematic method for relating the parameter labelling the marginal boundary deformation in the conformal field theory to the parameter labelling the classical solution in open string field theory. This is done by first constructing the energy-momentum tensor associated with the classical solution in open string field theory using Noether method, and then comparing this to the answer obtained in the conformal field theory by analysing the boundary state. We also use this method to demonstrate that in open string field theory the tachyon lump solution on a circle of radius larger than one has vanishing pressure along the circle direction, as is expected for a co-dimension one D-brane. (author)

Current density waves in open mesoscopic rings driven by time-periodic magnetic fluxes

International Nuclear Information System (INIS)

Yan Conghua; Wei Lianfu

2010-01-01

Quantum coherent transport through open mesoscopic Aharonov-Bohm rings (driven by static fluxes) have been studied extensively. Here, by using quantum waveguide theory and the Floquet theorem we investigate the quantum transport of electrons along an open mesoscopic ring threaded by a time-periodic magnetic flux. We predicate that current density waves could be excited along such an open ring. As a consequence, a net current could be generated along the lead with only one reservoir, if the lead additionally connects to such a normal-metal loop driven by the time-dependent flux. These phenomena could be explained by photon-assisted processes, due to the interaction between the transported electrons and the applied oscillating external fields. We also discuss how the time-average currents (along the ring and the lead) depend on the amplitude and frequency of the applied oscillating fluxes.

Selective labeling of a single organelle by using two-photon conversion of a photoconvertible fluorescent protein

Science.gov (United States)

Watanabe, Wataru; Shimada, Tomoko; Matsunaga, Sachihiro; Kurihara, Daisuke; Arimura, Shin-ichi; Tsutsumi, Nobuhiro; Fukui, Kiichi; Itoh, Kazuyoshi

2008-02-01

We present space-selective labeling of organelles by using two-photon conversion of a photoconvertible fluorescent protein with near-infrared femtosecond laser pulses. Two-photon excitation of photoconvertible fluorescent-protein, Kaede, enables space-selective labeling of organelles. We alter the fluorescence of target mitochondria in a tobacco BY-2 cell from green to red by focusing femtosecond laser pulses with a wavelength of 750 nm.

Crossover And MTF Characteristics Of A Tabular-Grain X-Ray Film

Science.gov (United States)

Huff, K. E.; Wagner, P. W.

1984-08-01

An orthochromatic x-ray film made with tabular silver halide grains has a significantly higher MTF when exposed with green-emitting intensifying screens than do conventional films with similar sensitometric properties. The primary reason for the improved MTF is a decrease in the amount of crossover exposure, i.e., exposure by light that has crossed the support one or more times. Two well-established sensitometric procedures for measuring crossover have been compared. One produces results accurate enough for calculations of MTF relationships. Calculated MTF relationships for tabulargrain and conventional films are compared with measured values.

Open-label pilot study of memantine in the treatment of compulsive buying.

Science.gov (United States)

Grant, Jon E; Odlaug, Brian L; Mooney, Marc; O'Brien, Robert; Kim, Suck Won

2012-05-01

Although compulsive buying (CB) is relatively common, pharmacotherapy research for CB is limited. Memantine, an N-methyl-D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive behaviors, suggesting it may help individuals with CB. Nine patients (8 females) with CB were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/d). Participants were enrolled from December 2008 until May 2010. The primary outcome measure was change from baseline to study endpoint on the Yale-Brown Obsessive Compulsive Scale-Shopping Version (Y-BOCS-SV). Of the 9 participants, 8 (88.9%) completed the 10-week study. Y-BOCS-SV scores decreased from a mean of 22.0 ± 1.3 at baseline to 11.0 ± 5.3 at endpoint (P impulsive buying and improvements on cognitive tasks of impulsivity. In addition, the medication was well-tolerated. These findings suggest that pharmacologic manipulation of the glutamate system may target the impulsive behavior underlying CB. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

A Prospective Randomized, Double-Blind, Two-Period Crossover Pharmacokinetic Trial Comparing Green Coffee Bean Extract-A Botanically Sourced Caffeine-With a Synthetic USP Control.

Science.gov (United States)

Morton, Kayce; Knight, Katelin; Kalman, Douglas; Hewlings, Susan

2018-04-16

Coffee is a primary dietary source of the chlorogenic acids (CGAs) of phenolic compounds. Coffee contains caffeine and other phytonutrients, including CGAs. Caffeine on its own has been well characterized and descried pharmacokinetically in the literature, less so for CGAs. The purpose of this double-blind crossover study was to determine the comparative pharmacokinetics of CGAs with caffeine (natural extract) with synthetic caffeine (US Pharmacopeia [USP] standard). Sixteen healthy male subjects were randomly assigned to take 1 dose of product 1, 60 mg of botanically sourced caffeine from 480 mg of green coffee bean extract, or product 2, 60 mg of synthetic USP caffeine, with 5 days between. Blood analysis was done to determine the levels of CGA compounds, more specifically 3-, 4-, and 5-caffeoylquinic acid (CQA), and serum caffeine. The natural caffeine extract exhibited mean peak concentrations (C max ) of 3-CQA (11.4 ng/mL), 4-CQA (6.84 ng/mL), and 5-CQA (7.20 ng/mL). The mean systemic 4-hour exposure (AUC 0-4 h ) was 3-CQA (27.3 ng·h/mL), 4-CQA (16.1 ng·h/mL), and 5-CQA (15.7 ng·h/mL). The median t max was 3-CQA (1.00 hour), 4-CQA (1.00 hour), and 5-CQA (1.50 hours). The t max of caffeine was 0.75 hours (natural extract) and 0.63 hours (synthetic caffeine). C max and AUC 0-4 h of serum caffeine were statistically equivalent between products. The geometric least-squares mean ratios (GMRs) of C max and AUC 0-4 h of caffeine were 97.77% (natural extract) and 98.33% (synthetic caffeine). It would appear that CGA compounds from the natural caffeine extract are bioavailable, and 3-CGA may be the compound most absorbed. In addition, caffeine sourced from natural extract versus synthetic were statistically similar for pharmacokinetic parameters. There were no adverse events or safety concerns. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Effect of Micronutrients on Behavior and Mood in Adults with ADHD: Evidence from an 8-Week Open Label Trial with Natural Extension

Science.gov (United States)

Rucklidge, Julia; Taylor, Mairin; Whitehead, Kathryn

2011-01-01

Objective: To investigate the effect of a 36-ingredient micronutrient formula consisting mainly of minerals and vitamins in the treatment of adults with both ADHD and severe mood dysregulation (SMD). Method: 14 medication-free adults (9 men, 5 women; 18-55 years) with ADHD and SMD completed an 8-week open-label trial. Results: A minority reported…

Local and sex-specific biases in crossover vs. noncrossover outcomes at meiotic recombination hot spots in mice

Science.gov (United States)

de Boer, Esther; Jasin, Maria; Keeney, Scott

2015-01-01

Meiotic recombination initiated by programmed double-strand breaks (DSBs) yields two types of interhomolog recombination products, crossovers and noncrossovers, but what determines whether a DSB will yield a crossover or noncrossover is not understood. In this study, we analyzed the influence of sex and chromosomal location on mammalian recombination outcomes by constructing fine-scale recombination maps in both males and females at two mouse hot spots located in different regions of the same chromosome. These include the most comprehensive maps of recombination hot spots in oocytes to date. One hot spot, located centrally on chromosome 1, behaved similarly in male and female meiosis: Crossovers and noncrossovers formed at comparable levels and ratios in both sexes. In contrast, at a distal hot spot, crossovers were recovered only in males even though noncrossovers were obtained at similar frequencies in both sexes. These findings reveal an example of extreme sex-specific bias in recombination outcome. We further found that estimates of relative DSB levels are surprisingly poor predictors of relative crossover frequencies between hot spots in males. Our results demonstrate that the outcome of mammalian meiotic recombination can be biased, that this bias can vary depending on location and cellular context, and that DSB frequency is not the only determinant of crossover frequency. PMID:26251527

The Effect of Medicinal Cannabis on Pain and Quality-of-Life Outcomes in Chronic Pain: A Prospective Open-label Study.

Science.gov (United States)

Haroutounian, Simon; Ratz, Yael; Ginosar, Yehuda; Furmanov, Karina; Saifi, Fayez; Meidan, Ronit; Davidson, Elyad

2016-12-01

The objective of this prospective, open-label study was to determine the long-term effect of medicinal cannabis treatment on pain and functional outcomes in participants with treatment-resistant chronic pain. The primary outcome was the change in the pain symptom score on the S-TOPS (Treatment Outcomes in Pain Survey-Short Form) questionnaire at the 6-month follow-up in an intent-to-treat population. Secondary outcomes included the change in S-TOPS physical, social, and emotional disability scales, the pain severity, and pain interference on the Brief Pain Inventory, sleep problems, and the change in opioid consumption. A total of 274 participants were approved for treatment; complete baseline data were available for 206 (intent-to-treat), and complete follow-up data for 176 participants. At follow-up, the pain symptom score improved from median 83.3 (95% confidence interval [CI], 79.2-87.5) to 75.0 (95% CI, 70.8-79.2) (Pmedicinal cannabis in this open-label, prospective cohort resulted in improved pain and functional outcomes, and a significant reduction in opioid use. Results suggest long-term benefit of cannabis treatment in this group of patients, but the study's noncontrolled nature should be considered when extrapolating the results.

Dimensional BCS-BEC crossover in ultracold Fermi gases

Energy Technology Data Exchange (ETDEWEB)

Boettcher, Igor

2014-12-10

We investigate thermodynamics and phase structure of ultracold Fermi gases, which can be realized and measured in the laboratory with modern trapping techniques. We approach the subject from a both theoretical and experimental perspective. Central to the analysis is the systematic comparison of the BCS-BEC crossover of two-component fermions in both three and two dimensions. A dimensional reduction can be achieved in experiments by means of highly anisotropic traps. The Functional Renormalization Group (FRG) allows for a description of both cases in a unified theoretical framework. In three dimensions we discuss with the FRG the influence of high momentum particles onto the density, extend previous approaches to the Unitary Fermi Gas to reach quantitative precision, and study the breakdown of superfluidity due to an asymmetry in the population of the two fermion components. In this context we also investigate the stability of the Sarma phase. For the two-dimensional system scattering theory in reduced dimension plays an important role. We present both the theoretically as well as experimentally relevant aspects thereof. After a qualitative analysis of the phase diagram and the equation of state in two dimensions with the FRG we describe the experimental determination of the phase diagram of the two-dimensional BCS-BEC crossover in collaboration with the group of S. Jochim at PI Heidelberg.

A Case Study of Controlling Crossover in a Selection Hyper-heuristic Framework Using the Multidimensional Knapsack Problem.

Science.gov (United States)

Drake, John H; Özcan, Ender; Burke, Edmund K

2016-01-01

Hyper-heuristics are high-level methodologies for solving complex problems that operate on a search space of heuristics. In a selection hyper-heuristic framework, a heuristic is chosen from an existing set of low-level heuristics and applied to the current solution to produce a new solution at each point in the search. The use of crossover low-level heuristics is possible in an increasing number of general-purpose hyper-heuristic tools such as HyFlex and Hyperion. However, little work has been undertaken to assess how best to utilise it. Since a single-point search hyper-heuristic operates on a single candidate solution, and two candidate solutions are required for crossover, a mechanism is required to control the choice of the other solution. The frameworks we propose maintain a list of potential solutions for use in crossover. We investigate the use of such lists at two conceptual levels. First, crossover is controlled at the hyper-heuristic level where no problem-specific information is required. Second, it is controlled at the problem domain level where problem-specific information is used to produce good-quality solutions to use in crossover. A number of selection hyper-heuristics are compared using these frameworks over three benchmark libraries with varying properties for an NP-hard optimisation problem: the multidimensional 0-1 knapsack problem. It is shown that allowing crossover to be managed at the domain level outperforms managing crossover at the hyper-heuristic level in this problem domain.

Engineering of spatial solitons in two-period QPM structures

DEFF Research Database (Denmark)

Johansen, Steffen Kjær; Carrasco, Silvia; Torner, Lluis

2002-01-01

We report on a scheme which might make it practically possible to engineer the effective competing nonlinearities that on average govern the light propagation in quasi-phase-matching (QPM) gratings. Modulation of the QPM period with a second longer period, introduces an extra degree of freedom...... relative lengths of the two periods and we consider the effect on solitons and the bandwidth for their generation. We derive an expression for the bandwidth of multicolor soliton generation in two-period QPM samples and we predict and confirm numerically that the bandwidth is broader in the two-period QPM...

Double-label autoradiographic deoxyglucose method for sequential measurement of regional cerebral glucose utilization

Energy Technology Data Exchange (ETDEWEB)

Redies, C; Diksic, M; Evans, A C; Gjedde, A; Yamamoto, Y L

1987-08-01

A new double-label autoradiographic glucose analog method for the sequential measurement of altered regional cerebral metabolic rates for glucose in the same animal is presented. This method is based on the sequential injection of two boluses of glucose tracer labeled with two different isotopes (short-lived /sup 18/F and long-lived /sup 3/H, respectively). An operational equation is derived which allows the determination of glucose utilization for the time period before the injection of the second tracer; this equation corrects for accumulation and loss of the first tracer from the metabolic pool occurring after the injection of the second tracer. An error analysis of this operational equation is performed. The double-label deoxyglucose method is validated in the primary somatosensory (''barrel'') cortex of the anesthetized rat. Two different rows of whiskers were stimulated sequentially in each rat; the two periods of stimulation were each preceded by an injection of glucose tracer. After decapitation, dried brain slices were first exposed, in direct contact, to standard X-ray film and then to uncoated, ''tritium-sensitive'' film. Results show that the double-label deoxyglucose method proposed in this paper allows the quantification and complete separation of glucose utilization patterns elicited by two different stimulations sequentially applied in the same animal.

Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial

OpenAIRE

Locatelli, Franco; Bernardo, Maria Ester; Bertaina, Alice; Rognoni, Carla; Comoli, Patrizia; Rovelli, Attilio; Pession, Andrea; Fagioli, Franca; Favre, Claudio; Lanino, Edoardo; Giorgiani, Giovanna; Merli, Pietro; Pagliara, Daria; Prete, Arcangelo; Zecca, Marco

2017-01-01

Background Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immunemediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II–IV acute graft-versus-host disease (GVHD). Methods We conducted a multicentre, randomised, open-label, p...

Solid state NMR and bioequivalence comparison of the pharmacokinetic parameters of two formulations of clindamycin

KAUST Repository

Al-Talla, Zeyad

2011-01-01

Objective: The purpose of this study was to compare the pharmacokinetic parameters and determine the bioequivalence of a generic formulation of clindamycin that is sold in the local markets in the Middle East (Clindox® 150 mg capsule; test) with a reference formulation (Dalacin C® 150 mg capsule) in healthy adult male volunteers. Methods: A single-dose, open-label, 2-period crossover study was conducted. Healthy male volunteers were randomly assigned to oral administration of a single treatment of the reference and test formulations. The same groups were given the alternate formulation. After dosing, serial blood samples were withdrawn for a period of 24 h. Serum harvested from the blood samples was analyzed for clindamycin by high performance liquid chromatography (HPLC) with ultraviolet detection. Pharmacokinetic parameters, including AUC0-∞, AUC 0-t, Cmax, Ke, tmax and t 1/2 were determined from the serum concentrations for both formulations (test and reference). The products were tested for bioequivalence after log-transformation of the data. Results: 24 healthy adult male volunteers from Jordan (mean [SD] age, 28.8 (7.7) years (range 19-45 years); height, 175.8 (10.6) cm (range 159.0-192.0 cm); weight, 75.6 (11.0) kg (range 58-101 kg); and body mass index, 24.4 (1.8) kg/m2 (range 21.3-28 kg/m2)) were enrolled in and completed the study. The 13C NMR spectra for both Dalacin C® and Clindox® showed 18 distinct lines associated with the 18 different carbon atoms. Conclusion: The statistical comparison suggested that Clindox® capsules are bioequivalent to Dalacin C® capsules. The 13C CPMAS results confirmed that the two drugs exhibit typical clindamycin spectra. ©2011 Dustri-Verlag Dr. K. Feistle.

Development of methanol evaporation plate to reduce methanol crossover in a direct methanol fuel cell

Science.gov (United States)

Zhang, Ruiming

This research focuses on methanol crossover reduction in direct methanol fuel cells (DMFC) through separating the methanol vapor from its liquid phase and feeding the vapor passively at low temperature range. Membrane electrode assemblies (MEAs) were fabricated by using commercial available membrane with different thickness at different anode catalyst loading levels, and tested under the operating conditions below 100°C in cell temperature and cathode exit open to ambient pressure. Liquid methanol transport from the anode through the membrane into cathode ("methanol crossover") is identified as one of the major efficiency losses in a DMFC. It is known that the methanol crossover rate in the vapor phase is much lower than in liquid phase. Vapor feed can be achieved by heating the liquid methanol to elevated temperatures (>100°C), but other issues limit the performance of the cell when operating above 100°C. High temperature membranes and much more active cathode catalyst structures are required, and a complex temperature control system must be employed. However, methanol vapor feed can also occur at a lower temperature range (evaporation through a porous body. The methanol crossover with this vapor feed mode is lower compared with the direct liquid methanol feed. A new method of using a methanol evaporation plate (MEP) to separate the vapor from its liquid phase to reduce the liquid methanol crossover at low temperature range is developed. A MEP plays the roles of liquid/vapor methanol phase separation and evaporation in a DMFC. The goal of this study is to develop a MEP with the proper properties to achieve high methanol phase separation efficiency and fast methanol evaporation rate over a wide range of temperature, i.e., from room temperature up to near boiling temperature (100°C). MEP materials were selected and characterized. MEPs made from three different types were tested extensively with different MEA and porous back layer configurations. The benefits of

A microscopic model of ballistic-diffusive crossover

International Nuclear Information System (INIS)

Bagchi, Debarshee; Mohanty, P K

2014-01-01

Several low-dimensional systems show a crossover from diffusive to ballistic heat transport when system size is decreased. Although there is some phenomenological understanding of this crossover phenomenon at the coarse-grained level, a microscopic picture that consistently describes both the ballistic and the diffusive transport regimes has been lacking. In this work we derive a scaling form for the thermal current in a class of one dimensional systems attached to heat baths at boundaries and rigorously show that the crossover occurs when the characteristic length scale of the system competes with the system size. (paper)

A two emulsion autoradiographic technique and the discriminating of the three different types of labelling after double labelling with 3H- and 14C-thymidine

International Nuclear Information System (INIS)

Schultze, B.; Maurer, W.; Hagenbusch, H.

1976-01-01

The first part of the paper deals with a two emulsion autoradiographic technique for double labelling experiments with 3 H- and 14 C-thymidine which permits a clear discrimination of the different types of labelling. In the second part the application of this technique to cell kinetics studies is discussed. Accurate discrimination between the different types of labelling, namely purely 3 H-, purely 14 C- and double ( 3 H + 14 C) labelling, is only possible if the activity ratio of 3 H- to 14 C-thymidine is sufficiently high. This condition is necessary for a reliable distinction between those grains in the first emulsion which are due to true 3 H-labelling and spurious grains which are simultaneously produced in the same emulsion by 14 C-β- particles. Experiments are described to determine the required activity ratio of 3 H- to 14 C-thymidine. (author)

Exploration of two-dimensional bio-functionalized phosphorene nanosheets (black phosphorous) for label free haptoglobin electro-immunosensing applications

Science.gov (United States)

Tuteja, Satish K.; Neethirajan, Suresh

2018-04-01

We report on the development of an antibody-functionalized interface based on electrochemically active liquid-exfoliated two-dimensional phosphorene (Ph) nanosheets—also known as black phosphorous nanosheets—for the label-free electrochemical immunosensing of a haptoglobin (Hp) biomarker, a clinical marker of severe inflammation. The electrodeposition has been achieved over the screen-printed electrode (SPE) using liquid-assisted ultrasonically exfoliated black phosphorus nanosheets. Subsequently, Ph-SPEs bioconjugated with Hp antibodies (Ab), using electrostatic interactions via a poly-L-lysine linker for biointerface development. Electrochemical analysis demonstrates that the Ab-modified Ph-SPEs (Ab@Ph-SPE) exhibit enhanced electroconducting behavior as compared to the pristine electrodes. This Ab-functionalized phosphorene-based electrochemical immunosensor platform has demonstrated remarkable sensitivity and specificity, having a dynamic linear response range from 0.01-10 mg ml-1 for Hp in standard and serum samples with a low detection limit (˜0.011 mg ml-1) using the label-free electrochemical technique. The sensor electrodes were also studied with other closely relative interferents to investigate cross reactivity and specificity. This strategy opens up avenues to POC (point-of-care) and on-farm livestock disease monitoring technologies for multiplexed diagnosis in complex biological samples such as serum. The technique is simple in fabrication and provides an analytical response in less than 60 s.

Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study.

Science.gov (United States)

Lotan, Itay; Treves, Therese A; Roditi, Yaniv; Djaldetti, Ruth

2014-01-01

The use of cannabis as a therapeutic agent for various medical conditions has been well documented. However, clinical trials in patients with Parkinson disease (PD) have yielded conflicting results. The aim of the present open-label observational study was to assess the clinical effect of cannabis on motor and non-motor symptoms of PD. Twenty-two patients with PD attending the motor disorder clinic of a tertiary medical center in 2011 to 2012 were evaluated at baseline and 30 minutes after smoking cannabis using the following battery: Unified Parkinson Disease Rating Scale, visual analog scale, present pain intensity scale, Short-Form McGill Pain Questionnaire, as well as Medical Cannabis Survey National Drug and Alcohol Research Center Questionnaire. Mean (SD) total score on the motor Unified Parkinson Disease Rating Scale score improved significantly from 33.1 (13.8) at baseline to 23.2 (10.5) after cannabis consumption (t = 5.9; P effects of the drug were observed. The study suggests that cannabis might have a place in the therapeutic armamentarium of PD. Larger, controlled studies are needed to verify the results.

Six week open-label reboxetine treatment in children and adolescents with attention deficit hyperactivity disorder

Directory of Open Access Journals (Sweden)

Arabgol F

2007-10-01

Full Text Available Background: Attention Deficit Hyperactivity Disorder (ADHD is a common psychiatric disorder among children and adolescents. This disorder causes difficulties in academic, behavioral, emotional, social and family performance. Stimulants show robust efficacy and a good safety profile in children with this disorder, but a significant percent of ADHD children do not respond adequately or cannot tolerate the associated adverse effects with stimulants. Such difficulties highlight the need for alternative safe and effective medications in the treatment of this disorder. This open-label study assessed the effectiveness of reboxetine, a selective norepinephrine reuptake inhibitor, in children and adolescents with attention deficit hyperactivity disorder (ADHD."nMethods: Fifteen child and adolescent outpatients, aged 7 to 16 (Mean± SD=9.72±2.71 years, diagnosed with ADHD were enrolled in a six open-label study with reboxetine 4-6 mg/d. The principal measure of the outcome was the teacher and parent Attention Deficit Hyperactive Disorder Rating Scale (ADHD Rating Scale. Patients were assessed by a child psychiatrist at baseline, 2, 4 and 6 weeks of the medication started. Side effects questionnaire was used to detect side effects of reboxetine. Repeated measures Analysis of variance (ANOVA was done for comparison of Teacher and Parent ADHD Rating Scale scores during the intervention."nResults: Twelve of 15 (80% participants completed the treatment protocol. A significant decrease in ADHD symptoms on teacher (p=0.04 and parent (p=0.003 ADHD rating scale was noted. Adverse effects were mild to moderate in severity. The most common adverse effects were drowsiness/sedation and appetite decrease."nConclusion: The results of the current study suggest the effectiveness of reboxetine in the treatment of ADHD in children and adolescents. Double-blind, placebo-controlled studies and larger sample size with long duration of intervention are indicated to rigorously

Topical Ketamine 10% for Neuropathic Pain in Spinal Cord Injury Patients: An Open-Label Trial.

Science.gov (United States)

Rabi, Joseph; Minori, Joshua; Abad, Hasan; Lee, Ray; Gittler, Michelle

2016-01-01

Topical ketamine, an N-methyl-D-aspartate antagonist, has been shown to be effective in certain neuropathic pain syndromes. The objective of this study was to determine the efficacy of topical ketamine in spinal cord injury patients with neuropathic pain. An open label trial enrolled five subjects at an outpatient rehabilitation hospital with traumatic spinal cord injuries who had neuropathic pain at or below the level of injury. Subjects applied topical ketamine 10% three times a day for a two-week duration. Subjects recorded their numerical pain score-ranging from 0 to 10, with 0 representing "no pain, 5 representing "moderate pain," and 10 being described as "worst possible pain"-in a journal at the time of application of topical ketamine and one hour after application. Using a numerical pain scale allows for something as subjective as pain to be given an objective quantification. Subjects also recorded any occurrence of adverse events and level of satisfaction. All five subjects had a decrease in their numerical pain scale by the end of two weeks, ranging from 14% to 63%. The duration ranged from one hour in one subject to the next application in other subjects. There were no adverse effects. Overall, four out of the five subjects stated they were satisfied. Topical ketamine 10% is an effective neuropathic pain medicine in patients with spinal cord injuries; however, further studies need to be done with a placebo and larger sample size. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Phase transformations of under-cooled austenite of new bainitic materials for scissors crossovers

Directory of Open Access Journals (Sweden)

J. Pacyna

2008-07-01

Full Text Available The paper contains CCT diagrams presenting a transformation kinetics of under-cooled austenite from two new bainitic cast steels which the scissors crossovers for heavy-duty railway tracks (min. 230kN/axle at the speed up to 200 km/h are made of. The cooling ranges of UIC60 type railway tracks plot on the CCT diagrams indicate that there is a 100% bainitic structure in the scissors crossovers made of these cast steels as well, but mainly it would be a favourable for cracking resistance lower bainite. The achievable hardness of scissors crossovers made of new materials make it possible to use high–temperature tempering resulting in obtaining of good crack resistance. However one should provide a good quality of castings made.

Testing Two Nutrient Profiling Models of Labelled Foods and Beverages Marketed in Turkey.

Science.gov (United States)

Dikmen, Derya; Kızıl, Mevlüde; Uyar, Muhemmet Fatih; Pekcan, Gülden

2015-06-01

The objective of this study was to evaluate the nutrient profile of labelled foods and also understand the application of two international nutrient profiling models of labelled foods and beverages. WXYfm and NRF 9.3 nutrient profiling models were used to evaluate 3,171 labelled foods and beverages of 38 food categories and 500 different brands. According to the WXYfm model, pasta, grains and legumes and frozen foods had the best scores whereas oils had the worst scores. According to the NRF 9.3 model per 100 kcal, the best scores were obtained for frozen foods, grains and legumes and milk products whereas the confectionery foods had the worst scores. According to NRF 9.3 per serving size, grains and legumes had the best scores and flavoured milks had the worst scores. A comparison of WXYfm and NRF 9.3 nutrient profiling models ranked scores showed a high positive correlation (p=0.01). The two nutrient models evaluated yielded similar results. Further studies are needed to test other category specific nutrient profiling models in order to understand how different models behave. Copyright© by the National Institute of Public Health, Prague 2015.

Fundamentos y aplicaciones del diseño de casos cruzados Case-crossover design: Basic essentials and applications

Directory of Open Access Journals (Sweden)

Eduardo Carracedo-Martínez

2009-04-01

short-term, acute event. The present article outlines the basics of case-crossover designs, as well as their applications and limitations. The case-crossover design is based on exclusively selecting case subjects. To calculate relative risk, exposure during the period of time prior to the event (case period is compared against the same subject's exposure during one or more control periods. This method is only appropriate when the exposures are transient in time and have acute short-term effects. For exposures in which there is no trend, a unidirectional approach is the most frequent and consists of selecting one or more control periods prior to the case period. When the exposure displays a time trend (e.g., air pollution, a unidirectional approach will yield biased estimates, and therefore bidirectional case-crossover designs are used, which select control time intervals preceding and subsequent to that of the event. The case-crossover design is being increasingly used across a wide range of fields, including factors triggering traffic, occupational and domestic accidents and acute myocardial infarction, and those involved in air pollution and health and pharmacoepidemiology, among others. Insofar as data-analysis is concerned, case-crossover designs can generally be regarded as matched case-control studies and consequently conditional logistic regression can be applied. Lastly, this study analyzes practical examples of distinct applications of the case-crossover design.

Comparison of application of various crossovers in solving inhomogeneous minimax problem modified by Goldberg model

Science.gov (United States)

Kobak, B. V.; Zhukovskiy, A. G.; Kuzin, A. P.

2018-05-01

This paper considers one of the classical NP complete problems - an inhomogeneous minimax problem. When solving such large-scale problem, there appear difficulties in obtaining an exact solution. Therefore, let us propose getting an optimum solution in an acceptable time. Among a wide range of genetic algorithm models, let us choose the modified Goldberg model, which earlier was successfully used by authors in solving NP complete problems. The classical Goldberg model uses a single-point crossover and a singlepoint mutation, which somewhat decreases the accuracy of the obtained results. In the article, let us propose using a full two-point crossover with various mutations previously researched. In addition, the work studied the necessary probability to apply it to the crossover in order to obtain results that are more accurate. Results of the computation experiment showed that the higher the probability of a crossover, the higher the quality of both the average results and the best solutions. In addition, it was found out that the higher the values of the number of individuals and the number of repetitions, the closer both the average results and the best solutions to the optimum. The paper shows how the use of a full two-point crossover increases the accuracy of solving an inhomogeneous minimax problem, while the time for getting the solution increases, but remains polynomial.

Cancer Prevention Fellowship Program Application Period is Open until August 25 | Division of Cancer Prevention

Science.gov (United States)

The application period for the NCI Cancer Prevention Fellowship Program (CPFP) is open. Since 1987, CPFP has provided funding support for post-doctoral Fellows to train the next generation of researchers and leaders in the field. |

Transmission of light through periodic arrays of square holes : from a metallic wire mesh to an array of tiny holes

NARCIS (Netherlands)

Bravo-Abad, J.; Martin-Moreno, L.; Garcia-Vidal, F.J.; Hendry, E.; Gómez Rivas, J.

2007-01-01

A complete landscape is presented of the electromagnetic coupling between square holes forming a two-dimensional periodic array in a metallic film. By combining both experimental and theoretical results along with a first-principles Fano model, we study the crossover between the physics of metallic

Efficacy of tiotropium and indacaterol monotherapy and their combination on dynamic lung hyperinflation in COPD: a random open-label crossover study

Directory of Open Access Journals (Sweden)

Fujimoto K

2017-11-01

Full Text Available Keisaku Fujimoto,1 Haruna Yamazaki,2 Midori Ura,2 Yoshiaki Kitaguchi3 1Department of Clinical Laboratory Sciences, School of Health Sciences, 2Department of Biomedical Laboratory Science, Graduate School of Medicine, 3First Department of Internal Medicine, School of Medicine, Shinshu University, Matsumoto, Japan Background and objective: The difference in efficacy of long-acting muscarinic antagonists (LAMAs and long-acting β2-agonists (LABAs for dynamic lung hyperinflation (DLH in COPD is unclear. The purpose of this study was to elucidate the difference in efficacy of LAMA and LABA alone and the combination thereof for DLH. Subjects and methods: Thirty stable patients were enrolled and randomly divided into two groups following baseline measurements. One group was treated with 5 µg tiotropium (Respimat inhaler for 4 weeks following a 4-week treatment with 150 µg indacaterol, while the other group was treated with indacaterol for 4 weeks following a 4-week treatment with tiotropium. For both groups, these treatments were followed by a combination of the two drugs for 4 weeks. Pulmonary function tests, including DLH evaluated by metronome-paced incremental hyperventilation and exercise tolerance evaluated by the shuttle-walk test, were performed at the end of each treatment period. Results: In total, 23 patients completed this study. Both tiotropium and indacaterol alone significantly increased forced expiratory volume in 1 second, exercise tolerance, and improved health status. Tiotropium significantly improved DLH, but indacaterol did not. The combination therapy resulted in further improvements in lung function and exercise tolerance, but not in DLH. Conclusion: The efficacy of tiotropium in inhibiting DLH following metronome-paced incremental hyperventilation may be superior to that of 150 µg indacaterol, although the effects on airflow obstruction were the same, and the combination therapy showed further improvement in airflow

Spin crossover in Fe(phen)2(NCS)2 complexes on metallic surfaces

Science.gov (United States)

Gruber, Manuel; Miyamachi, Toshio; Davesne, Vincent; Bowen, Martin; Boukari, Samy; Wulfhekel, Wulf; Alouani, Mebarek; Beaurepaire, Eric

2017-03-01

In this review, we give an overview on the spin crossover of Fe(phen)2(NCS)2 complexes adsorbed on Cu(100), Cu2N/Cu(100), Cu(111), Co/Cu(111), Co(100), Au(100), and Au(111) surfaces. Depending on the strength of the interaction of the molecules with the substrates, the spin crossover behavior can be drastically changed. Molecules in direct contact with non-magnetic metallic surfaces coexist in both the high- and low-spin states but cannot be switched between the two. Our analysis shows that this is due to a strong interaction with the substrate in the form of a chemisorption that dictates the spin state of the molecules through its adsorption geometry. Upon reducing the interaction to the surface either by adding a second molecular layer or inserting an insulating thin film of Cu2N, the spin crossover behavior is restored and molecules can be switched between the two states with the help of scanning tunneling microscopy. Especially on Cu2N, the two states of single molecules are stable at low temperature and thus allow the realization of a molecular memory. Similarly, the molecules decoupled from metallic substrates in the second or higher layers display thermally driven spin crossover as has been revealed by X-ray absorption spectroscopy. Finally, we discuss the situation when the complex is brought into contact with a ferromagnetic substrate. This leads to a strong exchange coupling between the Fe spin in the high-spin state and the magnetization of the substrate as deduced from spin-polarized scanning tunneling spectroscopy and ab initio calculation.

Seismic isolation of two dimensional periodic foundations

International Nuclear Information System (INIS)

Yan, Y.; Mo, Y. L.; Laskar, A.; Cheng, Z.; Shi, Z.; Menq, F.; Tang, Y.

2014-01-01

Phononic crystal is now used to control acoustic waves. When the crystal goes to a larger scale, it is called periodic structure. The band gaps of the periodic structure can be reduced to range from 0.5 Hz to 50 Hz. Therefore, the periodic structure has potential applications in seismic wave reflection. In civil engineering, the periodic structure can be served as the foundation of upper structure. This type of foundation consisting of periodic structure is called periodic foundation. When the frequency of seismic waves falls into the band gaps of the periodic foundation, the seismic wave can be blocked. Field experiments of a scaled two dimensional (2D) periodic foundation with an upper structure were conducted to verify the band gap effects. Test results showed the 2D periodic foundation can effectively reduce the response of the upper structure for excitations with frequencies within the frequency band gaps. When the experimental and the finite element analysis results are compared, they agree well with each other, indicating that 2D periodic foundation is a feasible way of reducing seismic vibrations.

Quantum phase crossovers with finite atom number in the Dicke model

International Nuclear Information System (INIS)

Hirsch, J G; Castaños, O; Nahmad-Achar, E; López-Peña, R

2013-01-01

Two-level atoms interacting with a one-mode cavity field at zero temperature have order parameters which reflect the presence of a quantum phase transition at a critical value of the atom–cavity coupling strength. Two popular examples are the number of photons inside the cavity and the number of excited atoms. Coherent states provide a mean field description, which becomes exact in the thermodynamic limit. Employing symmetry-adapted (SA) SU(2) coherent states the quantum crossover, precursor of the critical behavior, can be described for a finite number of atoms. A variation after projection treatment, involving a numerical minimization of the SA energy surface, associates the quantum crossover with a discontinuity in the order parameters, which originates from competition between two local minima in the SA energy surface. Although this discontinuity is not present in finite systems, it provides a good description of 1/N effects in the observables. (paper)

Periodic Scarred States in Open Quantum Dots as Evidence of Quantum Darwinism

Science.gov (United States)

Burke, A. M.; Akis, R.; Day, T. E.; Speyer, Gil; Ferry, D. K.; Bennett, B. R.

2010-04-01

Scanning gate microscopy (SGM) is used to image scar structures in an open quantum dot, which is created in an InAs quantum well by electron-beam lithography and wet etching. The scanned images demonstrate periodicities in magnetic field that correlate to those found in the conductance fluctuations. Simulations have shown that these magnetic transform images bear a strong resemblance to actual scars found in the dot that replicate through the modes in direct agreement with quantum Darwinism.

Lactitol, a second-generation disaccharide for treatment of chronic portal-systemic encephalopathy. A double-blind, crossover, randomized clinical trial.

Science.gov (United States)

Uribe, M; Toledo, H; Perez, F; Vargas, F; Gil, S; Garcia-Ramos, G; Ravelli, G P; Guevara, L

1987-12-01

A double-blind crossover trial was performed to test the therapeutic usefulness and safety of lactitol, a beta-galactoside sorbitol, against lactose in 18 patients with chronic portal-systemic encephalopathy (PSE). The study included four periods: two for washout and two for lactitol and lactose administration. During washout periods, which lasted two weeks each, patients were stabilized with neomycin plus milk of magnesia. Lactitol and lactose were administered during four weeks each. Ten patients were randomly assigned to receive lactose (group A) and eight patients to receive lactitol (group B) first. PSE parameters, ie, mental state, number connection test performance, asterixis and blood ammonia levels were assessed fortnightly. Electroencephalographic tracings and stool pHs were evaluated at the end of each study period. After the first administration of lactose and lactitol, no statistically significant differences in PSE parameters were found. At the same stage, a significant stool acidification (P less than 0.05) was detected. It is concluded that lactitol seems to be safe and efficacious in treating patients with chronic PSE.

Study of Λ parameters and crossover phenomena in SU(N) x SU(N) sigma models in two dimensions

International Nuclear Information System (INIS)

Shigemitsu, J.; Kogut, J.B.

1981-01-01

The spin system analogues of recent studies of the string tension and Λ parameters of SU(N) gauge theories in 4 dimensions are carried out for the SU(N) x SU(N) and O(N) models in 2 dimensions. The relations between the Λ parameters of both the Euclidean and Hamiltonian formulation of the lattice models and the Λ parameter of the continuum models are obtained. The one loop finite renormalization of the speed of light in the lattice Hamiltonian formulations of the O(N) and SU(N) x SU(N) models is calculated. Strong coupling calculations of the mass gaps of these spin models are done for all N and the constants of proportionality between the gap and the Λ parameter of the continuum models are obtained. These results are contrasted with similar calculations for the SU(N) gauge models in 3+1 dimensions. Identifying suitable coupling constants for discussing the N → infinity limits, the numerical results suggest that the crossover from weak to strong coupling in the lattice O(N) models becomes less abrupt as N increases while the crossover for the SU(N) x SU(N) models becomes more abrupt. The crossover in SU(N) gauge theories also becomes more abrupt with increasing N, however, at an even greater rate than in the SU(N) x SU(N) spin models

Edge Antimagic Total Labeling on Two Copies of Path

Science.gov (United States)

Nurdin; Abrar, A. M.; Bhayangkara, A. R. M.; Muliani; Samsir, A. U.; Nahdi, M. R. An

2018-03-01

A graph G = (V(G), E(G)) denotes the vertex set and the edge set, respectively. A (p,q)-graph G is a graph such that |V(G) | = p and |E(G) | = q. Graph of order p and size q is called (a,d)-edge-anti magic total if there exists a bijection f : V(G) U E(G)→ {1,2,..., p + q} such that the edge weights w(u,v) = f(u) + f(uv) + f(v) form an arithmetic sequence {a, a + d, a + 2d,...,a + (q - 1)d} with the first term a and common difference d. Two copies of path is disjoint union of two path graph with same order (Pn ∪Pn ) denoted by 2Pn . In this paper we construct the (a,d)-edge-anti magic total labeling in two copies of path for some differences d.

An open-label trial of L-5-hydroxytryptophan in subjects with romantic stress.

Science.gov (United States)

Emanuele, Enzo; Bertona, Marco; Minoretti, Piercarlo; Geroldi, Diego

2010-01-01

This open-label trial assessed the clinical efficacy of L-5-hydroxytryptophan (5-HTP), a natural serotonin precursor, in nondepressed young subjects with high levels of romantic stress. Since both neurotrophins and serotonin have been linked to human romantic attachment, we sought to investigate the changes in serum brain-derived neurotrophic factor (BDNF) levels and platelet serotonin content in relation to the changes in romantic stress throughout the study. A total of 15 healthy subjects (11 females and 4 males, mean age: 23.3 ± 2.1 years) who experienced a recent romantic break-up or reported recent romantic problems took part in the study. The participants were treated openly for 6 weeks with L-5-hydroxytryptophan (60 mg Griffonia simplicifolia extract containing 12.8 mg 5-HTP b.i.d., Amorex, Coropharm, Villach, Austria). The subjects were evaluated at baseline, at 3 weeks and at the end of the 6-week trial using an adapted version of the Seiffge-Krenke's Problem Questionnaire. BDNF and platelet serotonin content were determined at baseline, at 3 weeks, and after the completion of the 6-week trial. We observed significant improvements in romantic stress scores from weeks 0 through 3 (p=0.007) but no further significant improvement was evident from weeks 3 through 6 (p=0.19). At 6 weeks, subjects had a significant increase from baseline in both BDNF and platelet serotonin values. Our data suggest that direct modulation of the serotonergic system may have use for the treatment of psychological suffering associated with unreciprocated romantic love.

Speech perception with mono- and quadrupolar electrode configurations: a crossover study.

NARCIS (Netherlands)

Mens, L.H.M.; Berenstein, C.K.

2005-01-01

OBJECTIVE: To study the effect of two multipolar electrode configurations on speech perception, pitch perception, and the intracochlear electrical field. STUDY DESIGN: Crossover design; within subject. SETTING: Tertiary referral center. PATIENTS: Eight experienced adult cochlear implant users.

Effects of tetrahydrocannabinol on balance and gait in patients with dementia: A randomised controlled crossover trial.

Science.gov (United States)

van den Elsen, Geke Ah; Tobben, Lieke; Ahmed, Amir Ia; Verkes, Robbert Jan; Kramers, Cornelis; Marijnissen, Radboud M; Olde Rikkert, Marcel Gm; van der Marck, Marjolein A

2017-02-01

Oral tetrahydrocannabinol (THC) is currently studied for its possible efficacy on dementia-related neuropsychiatric symptoms (NPS), but might lead to increased risk of falling. This was a randomised, double-blind, crossover study to evaluate the effects of THC on mobility in dementia patients. Eighteen community-dwelling patients ( M age =77 years) received 1.5 mg of oral THC twice daily and placebo, in random order, for three days, separated by a four-day washout. Balance and gait were assessed using SwayStar TM and GAITRite TM within two hours after administration, in two consecutive intervention periods, under the following conditions: standing with eyes open (EO) and eyes closed (EC), preferred speed walking with and without a cognitive dual task. THC significantly increased sway during standing EC (roll angle 0.32[±0.6]°, p=0.05; pitch angle 1.04[±1.5]°, p=0.009; pitch velocity 1.96[±3.3]°/s, p=0.02), but not during standing EO. During preferred speed walking, THC increased stride length (4.3[±5.4] cm, p=0.005) and trunk sway (pitch angle 1.18[±1.6]°, p=0.005). No effects were observed during dual task walking. No differences in the number and type of adverse events were found, and no falls occurred after administration of THC. This study showed that 3 mg of THC per day has a benign adverse event profile regarding mobility and was well tolerated by community-dwelling dementia patients.

Conductance of partially disordered graphene: crossover from temperature-dependent to field-dependent variable-range hopping

International Nuclear Information System (INIS)

Cheah, C Y; Jaurigue, L C; Kaiser, A B; Gómez-Navarro, C

2013-01-01

We report an analysis of low-temperature measurements of the conductance of partially disordered reduced graphene oxide, finding that the data follow a simple crossover scenario. At room temperature, the conductance is dominated by two-dimensional (2D) electric field-assisted, thermally driven (Pollak–Riess) variable-range hopping (VRH) through highly disordered regions. However, at lower temperatures T, we find a smooth crossover to follow the exp(−E 0 /E) 1/3 field-driven (Shklovskii) 2D VRH conductance behaviour when the electric field E exceeds a specific crossover value E C (T) 2D =(E a E 0 1/3 /3) 3/4 determined by the scale factors E 0 and E a for the high-field and intermediate-field regimes respectively. Our crossover scenario also accounts well for experimental data reported by other authors for three-dimensional disordered carbon networks, suggesting wide applicability. (paper)

Graceful, harmonious and magic type labelings relations and techniques

CERN Document Server

López, Susana C

2017-01-01

Aimed toward upper undergraduate and graduate students in mathematics, this book examines the foremost forms of graph labelings including magic, harmonious, and graceful labelings. An overview of basic graph theory concepts and notation is provided along with the origins of graph labeling. Common methods and techniques are presented introducing readers to links between graph labels. A variety of useful techniques are presented to analyze and understand properties of graph labelings. The classical results integrated with new techniques, complete proofs, numerous exercises, and a variety of open problems, will provide readers with a solid understanding of graph labelings.

The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals

NARCIS (Netherlands)

van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Wit, F. W.; Lange, J. M.; Danner, S. A.; Foudraine, N. A.; Kwakkelstein, M. O.; Reiss, P.; Beijnen, J. H.; Hoetelmans, R. M.

2000-01-01

OBJECTIVE: To investigate and to compare the steady-state plasma pharmacokinetics of nevirapine in a dosing regimen of 400 mg once daily versus 200 mg twice daily in HIV-1-infected individuals. DESIGN: Open-label, randomized, cross-over study. METHODS: Twenty HIV-1-infected individuals who already

Pressure and Temperature Spin Crossover Sensors with Optical Detection

Science.gov (United States)

Linares, Jorge; Codjovi, Epiphane; Garcia, Yann

2012-01-01

Iron(II) spin crossover molecular materials are made of coordination centres switchable between two states by temperature, pressure or a visible light irradiation. The relevant macroscopic parameter which monitors the magnetic state of a given solid is the high-spin (HS) fraction denoted nHS, i.e., the relative population of HS molecules. Each spin crossover material is distinguished by a transition temperature T1/2 where 50% of active molecules have switched to the low-spin (LS) state. In strongly interacting systems, the thermal spin switching occurs abruptly at T1/2. Applying pressure induces a shift from HS to LS states, which is the direct consequence of the lower volume for the LS molecule. Each material has thus a well defined pressure value P1/2. In both cases the spin state change is easily detectable by optical means thanks to a thermo/piezochromic effect that is often encountered in these materials. In this contribution, we discuss potential use of spin crossover molecular materials as temperature and pressure sensors with optical detection. The ones presenting smooth transitions behaviour, which have not been seriously considered for any application, are spotlighted as potential sensors which should stimulate a large interest on this well investigated class of materials. PMID:22666041

Crossover Phenomena in Detrended Fluctuation Analysis Used in Financial Markets

International Nuclear Information System (INIS)

Ma Shihao

2009-01-01

A systematic analysis of Shanghai and Japan stock indices for the period of Jan. 1984 to Dec. 2005 is performed. After stationarity is verified by ADF (Augmented Dickey-Fuller) test, the power spectrum of the data exhibits a power law decay as a whole characterized by 1/f β processes with possible long range correlations. Subsequently, by using the method of detrended fluctuation analysis (DFA) of the general volatility in the stock markets, we find that the long-range correlations are occurred among the return series and the crossover phenomena exhibit in the results obviously. Further, Shanghai stock market shows long-range correlations in short time scale and shows short-range correlations in long time scale. Whereas, for Japan stock market, the data behaves oppositely absolutely. Last, we compare the varying of scale exponent in large volatility between two stock markets. All results obtained may indicate the possibility of characteristic of multifractal scaling behavior of the financial markets.

The joy of six: how to control your crossovers.

Science.gov (United States)

Globus, Samuel T; Keeney, Scott

2012-03-30

Meiotic cells tightly regulate the number and distribution of crossovers to promote accurate chromosome segregation. Yokoo and colleagues uncover a metazoan-specific, cyclin-like protein that is crucial for crossover formation. They utilize this protein's unique properties to explore a remarkable example of biological numerology, whereby nearly every meiotic cell in C. elegans makes precisely six crossovers, one for each of its six chromosome pairs. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinostatic rotation decreases crossover frequencies in the fungus Sordaria macrospora Auersw.

Science.gov (United States)

Henkel, J; Hock, B

1991-12-01

Two-factor crosses between the non-allelic spore colour mutants r2 and lu of the fungus Sordaria macrospora were used to investigate the effect of clinostatic rotation (= simulated weightlessness) on crossover frequencies. The experiment was carried out with different rotary directions at a rotary rate of 4 rpm. Second-division segregations of the gene lu, which result from crossover between the gene locus and centromere, are significantly smaller in the clinostat experiments than in the static controls. No differences were found between the two rotary directions. A similar influence of clinostatic rotation was not observed for the gene r2 which in contrast to the lu locus is located very close to the centromere. The suitability of this approach for the investigation of the effect of space flight conditions on cytogenetic processes is pointed out.

Crossover of burnout and engagement in work teams

NARCIS (Netherlands)

Bakker, A.B.; Van Emmerik, IJ.H.; Euwema, M.C.

2005-01-01

This study investigates the crossover of burnout and work engagement among 2,229 Royal Dutch constabulary officers, working in one of 85 teams. The authors hypothesized that both states may transfer from teams to individual team members. The results of multilevel analyses confirm this crossover

Ground-state fidelity in the BCS-BEC crossover

International Nuclear Information System (INIS)

Khan, Ayan; Pieri, Pierbiagio

2009-01-01

The ground-state fidelity has been introduced recently as a tool to investigate quantum phase transitions. Here, we apply this concept in the context of a crossover problem. Specifically, we calculate the fidelity susceptibility for the BCS ground-state wave function, when the intensity of the fermionic attraction is varied from weak to strong in an interacting Fermi system, through the BCS-Bose-Einstein Condensation crossover. Results are presented for contact and finite-range attractive potentials and for both continuum and lattice models. We conclude that the fidelity susceptibility can be useful also in the context of crossover problems.

NMR studies of two spliced leader RNAs using isotope labeling

Energy Technology Data Exchange (ETDEWEB)

Lapham, J.; Crothers, D.M. [Yale Univ., New Haven, CT (United States)

1994-12-01

Spliced leader RNAs are a class of RNA molecules (<200 nts) involved in the trans splicing of messenger RNA found in trypanosomes, nematodes, and other lower eukaryotes. The spliced leader RNA from the trypanosome Leptomonas Collosoma exists in two alternate structural forms with similar thermal stabilities. The 54 nucleotides on the 5{prime} end of the SL molecule is structurally independent from the 3{prime} half of the RNA, and displays the two structural forms. Furthermore, the favored of the two structures was shown to contain anomalous nuclease sensitivity and thermal stability features, which suggests that there may be tertiary interactions between the splice site and other nucleotides in the 5{prime} end. Multidimensional NMR studies are underway to elucidate the structural elements present in the SL RNAs that give rise to their physical properties. Two spliced leader sequences have been studied. The first, the 54 nucleotides on the 5{prime} end of the L. Collosoma sequence, was selected because of earlier studies in our laboratory. The second sequence is the 5{prime} end of the trypanosome Crithidia Fasciculata, which was chosen because of its greater sequence homology to other SL sequences. Given the complexity of the NMR spectra for RNA molecules of this size, we have incorporated {sup 15}N/{sup 13}C-labeled nucleotides into the RNA. One of the techniques we have developed to simplify the spectra of these RNA molecules is isotope labeling of specific regions of the RNA. This has been especially helpful in assigning the secondary structure of molecules that may be able to adopt multiple conformations. Using this technique one can examine a part of the molecule without spectral interference from the unlabeled portion. We hope this approach will promote an avenue for studying the structure of larger RNAs in their native surroundings.

Scalable In-Band Optical Notch-Filter Labeling for Ultrahigh Bit Rate Optical Packet Switching

DEFF Research Database (Denmark)

Medhin, Ashenafi Kiros; Galili, Michael; Oxenløwe, Leif Katsuo

2014-01-01

We propose a scalable in-band optical notch-filter labeling scheme for optical packet switching of high-bit-rate data packets. A detailed characterization of the notch-filter labeling scheme and its effect on the quality of the data packet is carried out in simulation and verified by experimental...... demonstrations. The scheme is able to generate more than 91 different labels that can be applied to 640-Gb/s optical time division multiplexed packets causing an eye opening penalty of $1.2-dB. Experimental demonstration shows that up to 256 packets can be uniquely labeled by employing up to eight notch filters...... with only 0.9-dB power penalty to achieve BER of 1E-9. Using the proposed labeling scheme, optical packet switching of 640 Gb/s data packets is experimentally demonstrated in which two data packets are labeled by making none and one spectral hole using a notch filter and are switched using a LiNbO$_3...

STAR POLYMERS IN GOOD SOLVENTS FROM DILUTE TO CONCENTRATED REGIMES: CROSSOVER APPROACH

Directory of Open Access Journals (Sweden)

S.B.Kiselev

2002-01-01

Full Text Available An introduction is given to the crossover theory of the conformational and thermodynamic properties of star polymers in good solvents. The crossover theory is tested against Monte Carlo simulation data for the structure and thermodynamics of model star polymers. In good solvent conditions, star polymers approach a "universal" limit as N → ∞, however, there are two types of approach towards this limit. In the dilute regime, a critical degree of polymerization N* is found to play a similar role as the Ginzburg number in the crossover theory for critical phenomena in simple fluids. A rescaled penetration function is found to control the free energy of star polymer solutions in the dilute and semidilute regions. This equation of state captures the scaling behaviour of polymer solutions in the dilute/semidilute regimes and also performs well in the concentrated regimes, where the details of the monomer-monomer interactions become important.

An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

DEFF Research Database (Denmark)

Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin

2013-01-01

This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

AAA-ATPase FIDGETIN-LIKE 1 and Helicase FANCM Antagonize Meiotic Crossovers by Distinct Mechanisms.

Directory of Open Access Journals (Sweden)

Chloe Girard

2015-07-01

Full Text Available Meiotic crossovers (COs generate genetic diversity and are critical for the correct completion of meiosis in most species. Their occurrence is tightly constrained but the mechanisms underlying this limitation remain poorly understood. Here we identified the conserved AAA-ATPase FIDGETIN-LIKE-1 (FIGL1 as a negative regulator of meiotic CO formation. We show that Arabidopsis FIGL1 limits CO formation genome-wide, that FIGL1 controls dynamics of the two conserved recombinases DMC1 and RAD51 and that FIGL1 hinders the interaction between homologous chromosomes, suggesting that FIGL1 counteracts DMC1/RAD51-mediated inter-homologue strand invasion to limit CO formation. Further, depleting both FIGL1 and the previously identified anti-CO helicase FANCM synergistically increases crossover frequency. Additionally, we showed that the effect of mutating FANCM on recombination is much lower in F1 hybrids contrasting from the phenotype of inbred lines, while figl1 mutation equally increases crossovers in both contexts. This shows that the modes of action of FIGL1 and FANCM are differently affected by genomic contexts. We propose that FIGL1 and FANCM represent two successive barriers to CO formation, one limiting strand invasion, the other disassembling D-loops to promote SDSA, which when both lifted, leads to a large increase of crossovers, without impairing meiotic progression.

Synthesizing labeled compounds

International Nuclear Information System (INIS)

London, R.E.; Matwiyoff, N.A.; Unkefer, C.J.; Walker, T.E.

1983-01-01

A metabolic study is presented of the chemical reactions provided by isotopic labeling and NMR spectroscopy. Synthesis of 13 C-labeled D-glucose, a 6-carbon sugar, involves adding a labeled nitrile group to the 5-carbon sugar D-arabinose by reaction with labeled hydrogen cyanide. The product of this reaction is then reduced and hydrolyzed to a mixture of the labeled sugars. The two sugars are separated by absorption chromotography. The synthesis of 13 C-labeled L-tyrosine, an amino acid, is also presented

A Bayesian analysis of the mixed labelling phenomenon in two-target tracking

NARCIS (Netherlands)

Aoki, E.H.; Boers, Y.; Svensson, L.; Mandal, Pranab K.; Bagchi, Arunabha

In mulit-target tracking and labelling (MTTL), mixed labelling corresponds to a situation where there is ambiguity in labelling, i.e. in the assignment of labels to locations (where a "location" here means simply an unlabelled single-target state. The phenomenon is well-known in literature, and

Pharmacokinetics of a telmisartan, amlodipine and ...

African Journals Online (AJOL)

Methods: This was a single-dose, randomized, open-label, replicate crossover study conducted in healthy male Korean ... FDCs containing the three drugs, and evaluate ... Subjects were forbidden from eating grape fruits ... who finished the study were used in the analysis ... regulations was conducted as an estimate of the.

Assessment of Relative Bioavailability of Moroctocog Alfa and Moroctocog Alfa (AF-CC) in Subjects With Severe Hemophilia A.

Science.gov (United States)

Korth-Bradley, Joan; Rupon, Jeremy; Plotka, Anna; Charnigo, Robert; Rendo, Pablo

2018-05-01

An open-label, single-dose, randomized, two-period, crossover study comparing the pharmacokinetics of factor VIII activity in plasma (FVIII:C) after administration of an albumin-free presentation of moroctocog alfa (test) and moroctocog alfa manufactured using the previous technique (reference) was conducted in 30 (25 evaluable) male subjects who had severe hemophilia A (FVIII:C < 1 IU/dL). Blood samples were collected for 48 h after administration of each dose. C was assayed using a chromogenic substrate assay. The FVIII:C pharmacokinetic parameters were calculated using noncompartmental analysis. The presentations would be bioequivalent if the 90% confidence limits of the ratio of the geometric mean values of AUC inf and recovery fell within the interval of 80-125%. The bioequivalence criteria were met. A total of 10 treatment-related adverse events were observed in a total of nine subjects. All were mild and none was determined to be related to administration of study medication. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design

Directory of Open Access Journals (Sweden)

Gao Joseph

2010-06-01

Full Text Available Abstract Background Duration of efficacy and safety of lisdexamfetamine dimesylate (LDX was assessed in adults (18-55 years with attention-deficit/hyperactivity disorder (ADHD using the simulated adult workplace environment. Methods After open-label dose optimization (4-week with LDX, 30-70 mg/d, subjects entered a 2-week randomized, double-blind, placebo-controlled crossover phase. Efficacy assessments included the Permanent Product Measure of Performance (PERMP total score (attempted+correct measured predose and from 2 to 14 hours postdose, averaged across postdose sessions (primary and at each time point vs placebo (secondary, and ADHD Rating Scale IV (ADHD-RS-IV with adult prompts at baseline and crossover visits. Safety assessments included treatment-emergent adverse events (TEAEs, vital signs, and electrocardiograms. Results Of 127 randomized subjects, 105 were in the intention-to-treat population and 103 completed the study. While receiving LDX vs placebo, adults had greater improvement (P P ≤ .0017 for each time point and change from predose (P P Conclusions LDX significantly improved PERMP scores vs placebo and maintained improvement throughout the day from the first (2 hours to last (14 hours postdose time point vs placebo in adults with ADHD. Trial Registration ClinicalTrials.gov Identifier: NCT00697515 Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX in Adults With Attention-Deficit Hyperactivity Disorder (ADHD http://www.clinicaltrials.gov/ct2/show/NCT00697515?term=NCT00697515&rank=1

Larmor labeling by time-gradient magnetic fields

International Nuclear Information System (INIS)

Ioffe, Alexander; Bodnarchuk, Victor; Bussmann, Klaus; Mueller, Robert

2007-01-01

The Larmor labeling of neutrons, due to the Larmor precession of neutron spin in a magnetic field, opens the unique possibility for the development of neutron spin-echo (NSE) based on neutron scattering techniques, featuring an extremely high energy (momentum) resolution. Here, we present the experimental proof of a new method of the Larmor labeling using time-gradient magnetic fields

Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a double-blind, randomized, open-label study [Corrigendum

Directory of Open Access Journals (Sweden)

Wani RA

2015-03-01

Full Text Available Wani RA, Dar MA, Chandel RK, et al Title of paper should have been “Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a randomized, open-label study”.  Read the original paper 

Eating marshmallows reduces ileostomy output: a randomized crossover trial.

Science.gov (United States)

Clarebrough, E; Guest, G; Stupart, D

2015-12-01

Anecdotally, many ostomates believe that eating marshmallows can reduce ileostomy effluent. There is a plausible mechanism for this, as the gelatine contained in marshmallows may thicken small bowel fluid, but there is currently no evidence that this is effective. This was a randomized crossover trial. Adult patients with well-established ileostomies were included. Ileostomy output was measured for 1 week during which three marshmallows were consumed three times daily, and for one control week where marshmallows were not eaten. There was a 2-day washout period. Patients were randomly allocated to whether the control or intervention week occurred first. In addition, a questionnaire was administered regarding patient's subjective experience of their ileostomy function. Thirty-one participants were recruited; 28 completed the study. There was a median reduction in ileostomy output volume of 75 ml per day during the study period (P = 0.0054, 95% confidence interval 23.4-678.3) compared with the control week. Twenty of 28 subjects (71%) experienced a reduction in their ileostomy output, two had no change and six reported an increase. During the study period, participants reported fewer ileostomy bag changes (median five per day vs six in the control period, P = 0.0255). Twenty of 28 (71%) reported that the ileostomy effluent was thicker during the study week (P = 0.023). Overall 19 (68%) participants stated they would use marshmallows in the future if they wanted to reduce or thicken their ileostomy output. Eating marshmallows leads to a small but statistically significant reduction in ileostomy output. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

The effect of physical training on patients with rheumatoid arthritis: changes in disease activity, muscle strength and aerobic capacity. A clinically controlled minimized cross-over study

DEFF Research Database (Denmark)

Lyngberg, K; Danneskiold-Samsøe, B; Halskov, O

1988-01-01

cross-over study the effect of graduated progressive training has been evaluated in 18 RA-patients with moderately active disease. The training was performed twice weekly with aerobic conditioning and strength exercises progressing to strenuous exercises over an 8-week period. The design was a crossover......For decades, physical training of rheumatoid arthritis (RA)-patients has been controversial, especially for patients with active disease. The aim of this study was to investigate whether RA-patients could receive graduated training without increasing the activity of the disease. In a controlled...... project with two groups obtained by minimisation. After training the patients had significantly fewer swollen joints than before. Training of the muscles acting over the swollen joints resulted in more than a 35% decrease in the number of swollen joints. The hemoglobin level increased significantly after...

An open-label, dose-titration tolerability study of atomoxetine hydrochloride in Japanese adults with attention-deficit/hyperactivity disorder.

Science.gov (United States)

Takahashi, Michihiro; Takita, Yasushi; Goto, Taro; Ichikawa, Hironobu; Saito, Kazuhiko; Matsumoto, Hideo; Tanaka, Yasuo

2011-02-01

The main purpose of this first atomoxetine study in Japanese adults with attention-deficit/hyperactivity disorder (ADHD) was to investigate the tolerability of an 8-week treatment regimen. This was an open-label, dose escalation study conducted in 45 Japanese patients aged at least 18 years with DSM-IV-defined ADHD. Patients received atomoxetine orally for 8 weeks. Atomoxetine administration was started at 40 mg/day (7 days), and subsequently increased to a maximum dose of 120 mg/day. Tolerability was assessed by discontinuation rate due to adverse events. Adverse events, laboratory tests, vital signs and electrocardiograms were collected. In addition, ADHD symptoms were assessed by using the Japanese version of the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) scores. Thirty-nine patients completed the study period. Atomoxetine was well tolerated with a 6.7% (3/45) discontinuation rate due to nausea, malaise and anorexia. The most commonly reported adverse events were nausea, nasopharyngitis and headache; there were no unexpected safety concerns. No deaths or serious adverse events were reported. Mean CAARS-Inv:SV-J total ADHD symptom scores decreased in a time-dependent manner; the mean change from baseline to endpoint was -15.0 (Patomoxetine was well tolerated in these patients and suggested that atomoxetine at a maximum dose of 120 mg/day would be safe in Japanese ADHD patients. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

The effects of a high protein diet on indices of health and body composition--a crossover trial in resistance-trained men.

Science.gov (United States)

Antonio, Jose; Ellerbroek, Anya; Silver, Tobin; Vargas, Leonel; Peacock, Corey

2016-01-01

Eight weeks of a high protein diet (>3 g/kg/day) coupled with a periodized heavy resistance training program has been shown to positively affect body composition with no deleterious effects on health. Using a randomized, crossover design, resistance-trained male subjects underwent a 16-week intervention (i.e., two 8-week periods) in which they consumed either their normal (i.e., habitual) or a higher protein diet (>3 g/kg/day). Thus, the purpose of this study was to ascertain if significantly increasing protein intake would affect clinical markers of health (i.e., lipids, kidney function, etc.) as well as performance and body composition in young males with extensive resistance training experience. Twelve healthy resistance-trained men volunteered for this study (mean ± SD: age 25.9 ± 3.7 years; height 178.0 ± 8.5 cm; years of resistance training experience 7.6 ± 3.6) with 11 subjects completing most of the assessments. In a randomized crossover trial, subjects were tested at baseline and after two 8-week treatment periods (i.e., habitual [normal] diet and high protein diet) for body composition, measures of health (i.e., blood lipids, comprehensive metabolic panel) and performance. Each subject maintained a food diary for the 16-week treatment period (i.e., 8 weeks on their normal or habitual diet and 8 weeks on a high protein diet). Each subject provided a food diary of two weekdays and one weekend day per week. In addition, subjects kept a diary of their training regimen that was used to calculate total work performed. During the normal and high protein phase of the treatment period, subjects consumed 2.6 ± 0.8 and 3.3 ± 0.8 g/kg/day of dietary protein, respectively. The mean protein intake over the 4-month period was 2.9 ± 0.9 g/kg/day. The high protein group consumed significantly more calories and protein (p protein group. There were no differences in dietary intake between the groups for any other measure

Synthesis of two tritium-labeled derivatives of a vasopressin antagonist peptide

International Nuclear Information System (INIS)

Landvatter, S.W.; Heys, J.R.

1986-01-01

SK and F 101926, a potent vasopressin antagonist, has been tritium labeled in the tyrosine residue via exchange followed by solid phase coupling to a hexapeptide. The peptide thus obtained was subsequently coupled with a PMP residue, cleaved from the resin with HF, oxidized by ferricyanide and purified by HPLC giving the desired cyclic peptide. Alternatively, a labeled PMP residue can be prepared via reduction starting from phenol. Conversion of the labeled cyclohexanone to PMP followed by solid phase coupling to a heptapeptide can then afford PMP labeled peptide. 3 refs

An Open-Label Evaluator Blinded Study of the Efficacy and Safety of a New Nutritional Supplement in Androgenetic Alopecia: A Pilot Study

OpenAIRE

Nichols, Anna J.; Hughes, Olivia Bosshardt; Canazza, Agnese; Zaiac, Martin N.

2017-01-01

Objective: To evaluate the effectiveness of a novel oral supplement, Forti5?, containing green tea extract, omega 3 and 6 fatty acids, cholecalciferol, melatonin, beta-sitosterol, and soy isoflavones, and in the management of subjects with androgenetic alopecia. Design: A prospective case series of 10 subjects. Setting: Open-label, evaluator-blinded, proof-of-concept study. Participants: Ten adult subjects with androgenetic alopecia completed the study. Subjects were not allowed to use oral o...

Effect of the Probiotic Saccharomyces boulardii on Cholesterol and Lipoprotein Particles in Hypercholesterolemic Adults: A Single-Arm, Open-Label Pilot Study.

Science.gov (United States)

Ryan, Jennifer Joan; Hanes, Douglas Allen; Schafer, Morgan Beth; Mikolai, Jeremy; Zwickey, Heather

2015-05-01

Elevated blood cholesterol levels are a major risk factor for coronary artery disease, the leading cause of death worldwide. Probiotics have been investigated as potential cholesterol-lowering therapies, but no previous studies have assessed the effect of the probiotic yeast Saccharomyces boulardii on cholesterol levels in human volunteers. The objective of this study was to examine the effect of S. boulardii on serum cholesterol and lipoprotein particles in hypercholesterolemic adults. This study was a single-arm, open-label pilot study. Twelve hypercholesterolemic participants were recruited into the study; one dropped out. Participants took 5.6×10(10) colony forming unit (CFU) encapsulated S. boulardii (Saccharomyces cerevisiae var. boulardii CNCM I-1079) twice daily for an 8-week period. Fasting concentrations of cholesterol (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], and triglycerides), lipoprotein particles (very-low-density lipoprotein-particle [VLDL-P], remnant lipoprotein particle [RLP-P], total LDL-P, LDL III-P, LDL IV-P, total HDL-P, and HDL 2b-P), and additional cardiovascular biomarkers (apo B-100, lipoprotein [a], high-sensitivity C-reactive protein, homocysteine, fibrinogen, and insulin) were measured at baseline, after 4 weeks, and after 8 weeks. Remnant lipoprotein particles decreased by 15.5% (p=0.03) over the 8-week period. The remaining outcome measures were not significantly altered. In this pilot study, 8 weeks of daily supplementation with S. boulardii lowered remnant lipoprotein, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease.

Effect of omega-3 polyunsaturated fatty acids on the cytoskeleton: an open-label intervention study.

Science.gov (United States)

Schmidt, Simone; Willers, Janina; Riecker, Sabine; Möller, Katharina; Schuchardt, Jan Philipp; Hahn, Andreas

2015-02-14

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) show beneficial effects on cardiovascular health and cognitive functions, but the underlying molecular mechanisms are not completely understood. Because of the fact that cytoskeleton dynamics affect almost every cellular process, the regulation of cytoskeletal dynamics could be a new pathway by which n-3 PUFAs exert their effects on cellular level. A 12-week open-label intervention study with 12 healthy men was conducted to determine the effects of 2.7 g/d n-3 PUFA on changes in mRNA expression of cytoskeleton-associated genes by quantitative real-time PCR in whole blood. Furthermore, the actin content in red blood cells was analyzed by immunofluorescence imaging. N-3 PUFA supplementation resulted in a significant down-regulation of cytoskeleton-associated genes, in particular three GTPases (RAC1, RHOA, CDC42), three kinases (ROCK1, PAK2, LIMK), two Wiskott-Aldrich syndrome proteins (WASL, WASF2) as well as actin related protein 2/3 complex (ARPC2, ARPC3) and cofilin (CFL1). Variability in F-actin content between subjects was high; reduced actin content was only reduced within group evaluation. Reduced cytoskeleton-associated gene expression after n-3 PUFA supplementation suggests that regulation of cytoskeleton dynamics might be an additional way by which n-3 PUFAs exert their cellular effects. Concerning F-actin, this analysis did not reveal unmistakable results impeding a generalized conclusion.

Synthetic food colourings and 'hyperactivity': a double-blind crossover study.

Science.gov (United States)

Rowe, K S

1988-04-01

Of 220 children referred for suspected 'hyperactivity', 55 were subjected to a 6 week trial of the Feingold diet. Forty (72.7%) demonstrated improved behaviour and 26 (47.3%) remained improved following liberalization of the diet over a period of 3-6 months. The parents of 14 children claimed that a particular cluster of behaviours was associated with the ingestion of foods containing synthetic colourings. A double-blind crossover study, employing a single-subject repeated measures design was conducted, using eight of these children. Subjects were maintained on a diet free from synthetic additives and were challenged daily for 18 weeks with either placebo (during lead-in and washout periods) or 50 mg of either tartrazine or carmoisine, each for 2 separate weeks. Two significant reactors were identified whose behavioural pattern featured extreme irritability, restlessness and sleep disturbance. One of the reactors did not have inattention as a feature. The findings raise the issue of whether the strict criteria for inclusion in studies concerned with 'hyperactivity' based on 'attention deficit disorder' may miss children who indicate behavioural changes associated with the ingestion of food colourings. Moreover, for further studies, the need to construct a behavioural rating instrument specifically validated for dye challenge is suggested.

Synthesis of two 14C-labeled catechol-o-methyltransferase inhibitors

International Nuclear Information System (INIS)

Karlsson, Carita; Honkanen, Erkki

1991-01-01

14 C-labelled 3-(3,4-dihydroxy-5-nitrophenylmethylidene)-2,4-pentanedione and 14 C-labelled E-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide have been synthesized from [carbonyl- 14 C]vanillin. (author)

Hydroxychloroquine treatment for primary Sjögren's syndrome: a two year double blind crossover trial

NARCIS (Netherlands)

Kruize, A. A.; Hené, R. J.; Kallenberg, C. G.; van Bijsterveld, O. P.; van der Heide, A.; Kater, L.; Bijlsma, J. W.

1993-01-01

In 1985 and 1988 a positive effect of treatment of primary Sjögren's syndrome with hydroxychloroquine was reported in two small open studies. To investigate further the clinical and laboratory effects of hydroxychloroquine in primary Sjögren's syndrome a two year study was performed. The design of

Two-step protein labeling by using lipoic acid ligase with norbornene substrates and subsequent inverse-electron demand Diels-Alder reaction.

Science.gov (United States)

Best, Marcel; Degen, Anna; Baalmann, Mathis; Schmidt, Tobias T; Wombacher, Richard

2015-05-26

Inverse-electron-demand Diels-Alder cycloaddition (DAinv ) between strained alkenes and tetrazines is a highly bio-orthogonal reaction that has been applied in the specific labeling of biomolecules. In this work we present a two-step labeling protocol for the site-specific labeling of proteins based on attachment of a highly stable norbornene derivative to a specific peptide sequence by using a mutant of the enzyme lipoic acid ligase A (LplA(W37V) ), followed by the covalent attachment of tetrazine-modified fluorophores to the norbornene moiety through the bio-orthogonal DAinv  . We investigated 15 different norbornene derivatives for their selective enzymatic attachment to a 13-residue lipoic acid acceptor peptide (LAP) by using a standardized HPLC protocol. Finally, we used this two-step labeling strategy to label proteins in cell lysates in a site-specific manner and performed cell-surface labeling on living cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantification and Sequencing of Crossover Recombinant Molecules from Arabidopsis Pollen DNA.

Science.gov (United States)

Choi, Kyuha; Yelina, Nataliya E; Serra, Heïdi; Henderson, Ian R

2017-01-01

During meiosis, homologous chromosomes undergo recombination, which can result in formation of reciprocal crossover molecules. Crossover frequency is highly variable across the genome, typically occurring in narrow hotspots, which has a significant effect on patterns of genetic diversity. Here we describe methods to measure crossover frequency in plants at the hotspot scale (bp-kb), using allele-specific PCR amplification from genomic DNA extracted from the pollen of F 1 heterozygous plants. We describe (1) titration methods that allow amplification, quantification and sequencing of single crossover molecules, (2) quantitative PCR methods to more rapidly measure crossover frequency, and (3) application of high-throughput sequencing for study of crossover distributions within hotspots. We provide detailed descriptions of key steps including pollen DNA extraction, prior identification of hotspot locations, allele-specific oligonucleotide design, and sequence analysis approaches. Together, these methods allow the rate and recombination topology of plant hotspots to be robustly measured and compared between varied genetic backgrounds and environmental conditions.

Effect of minoxidil topical foam on frontotemporal and vertex androgenetic alopecia in men: a 104-week open-label clinical trial.

Science.gov (United States)

Kanti, V; Hillmann, K; Kottner, J; Stroux, A; Canfield, D; Blume-Peytavi, U

2016-07-01

Topical minoxidil formulations have been shown to be effective in treating androgenetic alopecia (AGA) for 12 months. Efficacy and safety in both frontotemporal and vertex regions over longer application periods have not been studied so far. To evaluate the effect of 5% minoxidil topical foam (5% MTF) in the frontotemporal and vertex areas in patients with moderate AGA over 104 weeks. An 80-week, open-label extension phase was performed, following a 24-week randomized, double-blind, placebo-controlled study in men with AGA grade IIIvertex to VI. Group 1 (n = 22) received ongoing 5% MTF for 104 weeks, Group 2 (n = 23) received placebo topical foam (plaTF) until week 24, followed by 5% MTF until week 104 during the extension phase. Frontotemporal and vertex target area non-vellus hair counts (f-TAHC, v-TAHC) and cumulative hair width (f-TAHW, v-TAHW) were assessed at baseline and at weeks 24, 52, 76 and 104. In Group 1, f-TAHW and f-TAHC showed a statistically significant increase from baseline to week 52 and week 76, respectively, returning to values comparable to baseline at week 104. No significant differences were found between baseline and week 104 in v-TAHC in Group 1 as well as f-TAHC, v-TAHC, f-TAHW and v-TAHW values in Group 2. 5% MTF is effective in stabilizing hair density, hair width and scalp coverage in both frontotemporal and vertex areas over an application period of 104 weeks, while showing a good safety and tolerability profile with a low rate of irritant contact dermatitis. © 2015 European Academy of Dermatology and Venereology.

Assessment of inflammatory bowel disease with two different 99mTc-leucocytes labelling methods

International Nuclear Information System (INIS)

Cardoso, V.N.; Plaza, P.J.L.; Roca, M.; Armero, F.; Martin-Comin, J.

2002-01-01

Aim of this study was to retrospectively compare the diagnostic accuracy of 99mTc-HMPAO white blood cell scintigraphy using two different cell suspension mediums: leukocyte poor plasma (LPP) and Hanks' Balanced Salt Solution (HBSS) in patients with suspicion of active inflammatory bowel disease. Materials and Methods: Leukocytes from 30 patients were labelled using LPP and in 28 using HBSS . In LPP method the leukocytes were resuspended in 0,5 ml cell-free plasma while in HBSS method the cells were resuspended in 0,5 ml HBSS. Scintigraphic images were obtained at 30 min and 2 h after injection of 185-200 MBq 99mTc-HMPAO leukocytes. Results: Leukocytes labelling efficiency were 65,5%, and 89,0%, respectively for LPP and HBSS methods. There were 22 true-positive, 7 true-negative and 1 false-negative results in the LPP group, while in the HBSS group results were 18, 10 and 0, respectively. Diagnostic accuracy was similar with both methods though sensitivity was slightly higher in the HBSS group. Conclusion These date indicate that leukocytes scintigraphy labelled using HBSS as resuspension medium should be used as first option method for WBC labelling and diagnosis of inflammatory bowel disease

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial.

Science.gov (United States)

Tawbi, Hussein A; Burgess, Melissa; Bolejack, Vanessa; Van Tine, Brian A; Schuetze, Scott M; Hu, James; D'Angelo, Sandra; Attia, Steven; Riedel, Richard F; Priebat, Dennis A; Movva, Sujana; Davis, Lara E; Okuno, Scott H; Reed, Damon R; Crowley, John; Butterfield, Lisa H; Salazar, Ruth; Rodriguez-Canales, Jaime; Lazar, Alexander J; Wistuba, Ignacio I; Baker, Laurence H; Maki, Robert G; Reinke, Denise; Patel, Shreyaskumar

2017-11-01

Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. Chemotherapy and targeted therapies offer short-lived disease control. We assessed pembrolizumab, an anti-PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma. In this two-cohort, single-arm, open-label, phase 2 study, we enrolled patients with soft-tissue sarcoma or bone sarcoma from 12 academic centres in the USA that were members of the Sarcoma Alliance for Research through Collaboration (SARC). Patients with soft-tissue sarcoma had to be aged 18 years or older to enrol; patients with bone sarcoma could enrol if they were aged 12 years or older. Patients had histological evidence of metastatic or surgically unresectable locally advanced sarcoma, had received up to three previous lines of systemic anticancer therapy, had at least one measurable lesion according to the Response Evaluation Criteria In Solid Tumors version 1.1, and had at least one lesion accessible for biopsy. All patients were treated with 200 mg intravenous pembrolizumab every 3 weeks. The primary endpoint was investigator-assessed objective response. Patients who received at least one dose of pembrolizumab were included in the safety analysis and patients who progressed or reached at least one scan assessment were included in the activity analysis. Accrual is ongoing in some disease cohorts. This trial is registered with ClinicalTrials.gov, number NCT02301039. Between March 13, 2015, and Feb 18, 2016, we enrolled 86 patients, 84 of whom received pembrolizumab (42 in each disease cohort) and 80 of whom were evaluable for response (40 in each disease cohort). Median follow-up was 17·8 months (IQR 12·3-19·3). Seven (18%) of 40 patients with soft-tissue sarcoma had an objective response, including four (40%) of ten patients with undifferentiated pleomorphic sarcoma, two (20%) of ten patients with liposarcoma, and one (10%) of ten patients

A molecular beacon microarray based on a quantum dot label for detecting single nucleotide polymorphisms.

Science.gov (United States)

Guo, Qingsheng; Bai, Zhixiong; Liu, Yuqian; Sun, Qingjiang

2016-03-15

In this work, we report the application of streptavidin-coated quantum dot (strAV-QD) in molecular beacon (MB) microarray assays by using the strAV-QD to label the immobilized MB, avoiding target labeling and meanwhile obviating the use of amplification. The MBs are stem-loop structured oligodeoxynucleotides, modified with a thiol and a biotin at two terminals of the stem. With the strAV-QD labeling an "opened" MB rather than a "closed" MB via streptavidin-biotin reaction, a sensitive and specific detection of label-free target DNA sequence is demonstrated by the MB microarray, with a signal-to-background ratio of 8. The immobilized MBs can be perfectly regenerated, allowing the reuse of the microarray. The MB microarray also is able to detect single nucleotide polymorphisms, exhibiting genotype-dependent fluorescence signals. It is demonstrated that the MB microarray can perform as a 4-to-2 encoder, compressing the genotype information into two outputs. Copyright © 2015 Elsevier B.V. All rights reserved.

Do nutrition labels influence healthier food choices? Analysis of label viewing behaviour and subsequent food purchases in a labelling intervention trial.

Science.gov (United States)

Ni Mhurchu, Cliona; Eyles, Helen; Jiang, Yannan; Blakely, Tony

2018-02-01

There are few objective data on how nutrition labels are used in real-world shopping situations, or how they affect dietary choices and patterns. The Starlight study was a four-week randomised, controlled trial of the effects of three different types of nutrition labels on consumer food purchases: Traffic Light Labels, Health Star Rating labels, or Nutrition Information Panels (control). Smartphone technology allowed participants to scan barcodes of packaged foods and receive randomly allocated labels on their phone screen, and to record their food purchases. The study app therefore provided objectively recorded data on label viewing behaviour and food purchases over a four-week period. A post-hoc analysis of trial data was undertaken to assess frequency of label use, label use by food group, and association between label use and the healthiness of packaged food products purchased. Over the four-week intervention, study participants (n = 1255) viewed nutrition labels for and/or purchased 66,915 barcoded packaged products. Labels were viewed for 23% of all purchased products, with decreasing frequency over time. Shoppers were most likely to view labels for convenience foods, cereals, snack foods, bread and bakery products, and oils. They were least likely to view labels for sugar and honey products, eggs, fish, fruit and vegetables, and meat. Products for which participants viewed the label and subsequently purchased the product during the same shopping episode were significantly healthier than products where labels were viewed but the product was not subsequently purchased: mean difference in nutrient profile score -0.90 (95% CI -1.54 to -0.26). In a secondary analysis of a nutrition labelling intervention trial, there was a significant association between label use and the healthiness of products purchased. Nutrition label use may therefore lead to healthier food purchases. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Periodic trajectories for two-dimensional nonintegrable Hamiltonians

International Nuclear Information System (INIS)

Davies, K.T.R.

1990-02-01

I want to report on some calculations of classical periodic trajectories in a two-dimensional nonintegrable potential. After a brief introduction, I will present some details of the theory. The main part of this report will be devoted to showing pictures of the various families of trajectories and to discussing the topology (in E-τ space) and branching behavior of these families. Then I will demonstrate the connection between periodic trajectories and ''nearby'' nonperiodic trajectories, which nicely illustrates the relationship of this work to chaos. Finally, I will discuss very briefly how periodic trajectories can be used to calculate tori. 12 refs., 40 figs

Skating crossovers on a motorized flywheel: a preliminary experimental design to test effect on speed and on crossovers.

Science.gov (United States)

Smith, Aynsley M; Krause, David A; Stuart, Michael J; Montelpare, William J; Sorenson, Matthew C; Link, Andrew A; Gaz, Daniel V; Twardowski, Casey P; Larson, Dirk R; Stuart, Michael B

2013-12-01

Ice hockey requires frequent skater crossovers to execute turns. Our investigation aimed to determine the effectiveness of training crossovers on a motorized, polyethylene high-resistance flywheel. We hypothesized that high school hockey players training on the flywheel would perform as well as their peers training on ice. Participants were 23 male high-school hockey players (age 15-19 years). The study used an experimental prospective design to compare players who trained for 9 sessions on the 22-foot flywheel with players who trained for 9 sessions on a similarly sized on-ice circle. Both groups were compared with control subjects who were randomly selected from the same participant pool as those training on ice. All players were tested before and after their 3-week training regimens, and control subjects were asked to not practice crossovers between testing. Group 1 trained in a hockey training facility housing the flywheel, and group 2 trained in the ice hockey arena where testing occurred. Primary outcome measures tested in both directions were: (a) speed (time in seconds) required to skate crossovers for 3 laps of a marked face-off circle, (b) cadence of skating crossovers on the similarly sized circles, and (c) a repeat interval speed test, which measures anaerobic power. No significant changes were found between groups in on-ice testing before and after training. Among the group 1 players, 7 of 8 believed they benefited from flywheel training. Group 2 players, who trained on ice, did not improve performance significantly over group 1 players. Despite the fact that no significant on-ice changes in performance were observed in objective measures, players who trained on the flywheel subjectively reported that the flywheel is an effective cost-effective alternative to training on ice. This is a relevant finding when placed in context with limited availability of on-ice training.

Spin—Dependent Scattering Effects and Dimensional Crossover in a Quasi—Two—Dimensional Disordered Electron System

Institute of Scientific and Technical Information of China (English)

YANGYong－Hong; WANGYong－Gang; 等

2002-01-01

Two kinds of spin-dependent scattering effects (magnetic-impurity and spin-orbit scatterings) are investigated theoretically in a quasi-tow-dimensional (quasi-2D) disordered electron system.By making use of the diagrammatic techniques in perturbation theory,we have calculated the dc conductivity and magnetoresistance due to weak-localization effects,the analytical expressions of them are obtained as functions of the interlayer hopping energy and the characteristic times:elastic,inelastic,magnetic and spin-orbit scattering times.The relevant dimensional crossover behavior from 3D to 2D with decreasing the interlayer coupling is discussed,and the condition for the crossover is shown to be dependent on the aforementioned scattering times.At low temperature there exists a spin-dependent-scattering-induced dimensional crossover in this system.

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.

Science.gov (United States)

Spaeth, Michael; Alegre, Cayetano; Perrot, Serge; Wang, Youyu; Guinta, Diane R; Alvarez-Horine, Sarah; Russell, Irwin

2013-11-11

The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. ClinicalTrials.gov NCT00423605.

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

Science.gov (United States)

2013-01-01

Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. Conclusions The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. Trial registration ClinicalTrials.gov NCT00423605. PMID:24286114

A comparison of two procedures for labelling the surface of the hydatid disease organism, Echinococcus granulosus, with 125I

International Nuclear Information System (INIS)

McManus, D.P.; McLaren, D.J.; Clark, N.W.T.; Parkhouse, R.M.E.

1987-01-01

Living, intact protoscoleces of the British horse and sheep strains of Echinococcus granulosus were subjected to surface radioiodination procedures using 125 I and Iodogen and 125 I-Bolton Hunter reagent. Subsequent combined electron microscopy and autoradiography revealed specific surface membrane labelling with the Iodogen procedure, but significant tegumental labelling with the Bolton-Hunter reagent. The two parasite strains yielded different profiles of electrophoretically separated labelled proteins; the Iodogen method, not surprisingly, resulted in a less complex pattern of labelled polypeptides than the Bolton and Hunter reagent. (author)

Limit Cycles and Chaos via Quasi-periodicity in Two Coupled Ensembles of Ultra-cold Atoms.

Science.gov (United States)

Patra, Aniket; Yuzbashyan, Emil; Altshuler, Boris

We study the dynamics of two mesoscopic ensembles of ultra-cold two level atoms, which are collectively coupled to an optical cavity and are being pumped incoherently to the excited state. Whereas the time independent steady states are well understood, little is known about the time dependent ones. We explore and categorize various time dependent steady states, e.g. limit cycles and chaotic behavior. We draw a non-equilibrium phase diagram indicating different steady-state behaviors in different parts of the parameter space. We discuss the synchronization of the two ensembles in the time dependent steady states. We also show the onset of chaos via quasi-periodicity. The rich time dependent steady-state behavior, especially the existence of chaos, opens up possibilities for several engineering applications. Supported in part by the University and Louis Bevier Graduate Fellowship.

[Vaginitis and vaginosis. Comparison of two periods].

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Ceruti, M; Canestrelli, M; Piantelli, G; Amone, F; Condemi, V; De Paolis, P; Ludovici, G; Somenzi, P

1993-10-01

Vaginitis is the most frequent gynecological disease. It is characterized by objective and subjective signs of inflammation and differs from bacterial vaginosis (BV) which is an abnormal condition of the vaginal ecosystem caused by the excessive growth of aerobic and anaerobic flora normally present in the vagina with an increased risk of pelvic inflammatory disease (PID). The authors report the results of a study carried out at the Centre for Gynecological Infections at the Clinic of Obstetrics and Gynecology of the University of Parma. 828 patients were enrolled in the study during the period 1985-86 and 1559 patients during the two-year period 1991-92. The aim of the study was to evaluate variations in epidemiological data for vaginitis and bacterial vaginosis in the two periods examined. No significant changes were observed (p > 0.05) with regard to the prevalence of Ca, Tv and BV forms. On the other hand, there was a significant reduction (p vaginitis and BV showed a reduction of other microorganisms and an increase in negative vaginal swabs in adults (> 20 years old).

Individual and crossover effects of stress on adjustment in medical student marriages.

Science.gov (United States)

Katz, J; Monnier, J; Libet, J; Shaw, D; Beach, S R

2000-07-01

High-stress individuals may benefit from social support, although their support providers may be adversely affected via stress crossover effects. Individual and crossover effects of perceived stress within medical student marriages (n = 30) were investigated. Perceived spousal support was positively associated with individuals' own marital and emotional adjustment, attenuating stress effects. With regard to crossover effects, medical students' perceived stress was significantly associated with their spouses' emotional adjustment. Further, medical students' own emotional adjustment fully mediated this crossover effect. Results suggest that the contagion of negative affect may serve as a key mechanism through which stress crossover effects operate in marriage.

Treatment of a Common Iliac Aneurysm by Endovascular Exclusion Using the Amplatzer Vascular Plug and Femorofemoral Crossover Graft

International Nuclear Information System (INIS)

Coupe, Nicholas J.; Ling, Lynn; Cowling, Mark G.; Asquith, John R.; Hopkinson, Gregory B.

2009-01-01

We report our initial experience using the Amplatzer Vascular Plug II (AVP2) in the treatment of a left common iliac aneurysm. Following investigation by computerized tomographic angiography and catheter angiography, a 79-year-old man was found to have a markedly tortuous iliac system, with a left common iliac artery aneurysm that measured 48 mm in maximal diameter. Due to the patient's age and comorbidities the surgical opinion was that conventional open repair was not suitable. However, due to the tortuous nature of the aneurysm and iliac vessels, standard endovascular repair, using either a bifurcated or an aorto-uni-iliac stent graft, was also not possible. A combined approach was used by embolizing the ipsilateral internal iliac artery using coils and excluding the aneurysm using two AVP2 occlusion devices, followed by femorofemoral crossover grafting. Total aneurysm occlusion was achieved using this method and this allowed the patient to have a much less invasive surgical procedure than with conventional open repair of common iliac aneurysms, thus avoiding potential comorbidity and mortality.

A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

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Mason JW

2014-03-01

Full Text Available Jay W Mason,1 Thomas E Moon,2 Erin O’Boyle,3 Albert Dietz41Department of Medicine, University of Utah, Salt Lake City, UT, 2Tarizona eHealth Services, Inc., San Carlos, CA, 3AP Pharma, Redwood City, CA, 4Spaulding Clinical Research, West Bend, WI, USABackground: Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO, intravenous (IV, and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals.Methods: This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated.Results: The upper one-sided 95% confidence interval (CI for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36 at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours and slow elimination (mean half-life 18.6 hours

What's Mine Is Yours: The Crossover of Day-Specific Self-Esteem

Science.gov (United States)

Neff, Angela; Sonnentag, Sabine; Niessen, Cornelia; Unger, Dana

2012-01-01

This diary study examines the daily crossover of self-esteem within working couples. By integrating self-esteem research into the crossover framework, we hypothesized that the day-specific self-esteem experienced by one partner after work crosses over to the other partner. Furthermore, we proposed that this daily crossover process is moderated by…

Comparison of two procedures for labelling the surface of the hydatid disease organism, Echinococcus granulosus, with /sup 125/I

Energy Technology Data Exchange (ETDEWEB)

McManus, D.P.; McLaren, D.J.; Clark, N.W.T.; Parkhouse, R.M.E.

1987-03-01

Living, intact protoscoleces of the British horse and sheep strains of Echinococcus granulosus were subjected to surface radioiodination procedures using /sup 125/I and Iodogen and /sup 125/I-Bolton Hunter reagent. Subsequent combined electron microscopy and autoradiography revealed specific surface membrane labelling with the Iodogen procedure, but significant tegumental labelling with the Bolton-Hunter reagent. The two parasite strains yielded different profiles of electrophoretically separated labelled proteins; the Iodogen method, not surprisingly, resulted in a less complex pattern of labelled polypeptides than the Bolton and Hunter reagent.

A prospective, observational, open-label, multicentre study to investigate the daily treatment practice of ranibizumab in patients with neovascular age-related macular degeneration.

Science.gov (United States)

van Asten, Freekje; Evers-Birkenkamp, Kim U; van Lith-Verhoeven, Janneke J C; de Jong-Hesse, Yvonne; Hoppenreijs, Vincent P T; Hommersom, Richard F; Scholten, Agnes M; Hoyng, Carel B; Klaver, Johannes H J

2015-03-01

The HELIOS (Health Economics with Lucentis in Observational Settings) study was designed on request of the Dutch Health Authority for an observational study to assess the effectiveness and safety of ranibizumab for neovascular age-related macular degeneration (wet AMD) in daily practice. The HELIOS study was a 2-year prospective, observational, open-label, multicentre study involving 14 sites. Patients with wet AMD were enrolled and observed for a period of 24 months. The data were collected at baseline and at the visits closest around the time-points 3, 6, 12, 18 and 24 months after inclusion. Treatment with ranibizumab resulted in prevention of vision loss. The mean ETDRS score increased from 45.1 letters at baseline to 48.5 letters at 24 months. This was achieved with a mean of 7.8 injections over 24 months. Stabilization of visual acuity was also reflected by the scores on the quality of life EQ-5D questionnaire, which did not significantly change over the study period. The more subjective EQ-VAS questionnaire showed an overall improvement. The VFQ-25 questionnaire was also mostly stable over time. After 24 months, 32.2% of the patients gained ≥1 letter and 17.1% gained >15 letters. Patients completing the loading phase were better responders, as demonstrated by increased long-term visual acuity. In addition, ranibizumab was well tolerated and had a safety profile commonly seen in routine clinical practice. This study demonstrates that also in daily practice ranibizumab was effective in preventing vision loss over a period of 24 months. No new safety findings were identified. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Comparison of infrared-excited up-converting phosphors and europium nanoparticles as labels in a two-site immunoassay

International Nuclear Information System (INIS)

Ukonaho, Telle; Rantanen, Terhi; Jaemsen, Laura; Kuningas, Katri; Paekkilae, Henna; Loevgren, Timo; Soukka, Tero

2007-01-01

Research in the field of immunoassays and labels used in the detection has been recently focused on particulate reporters, which possess very high specific activity that excludes the label as a sensitivity limiting factor. However, the large size and shape of the particulate labels may produce additional problems to immunoassay performance. The aim of this work was to study with two identical non-competitive two-site immunoassays whether up-converting phosphor (UCP) particles are comparable in performance with europium(III) chelate-dyed nanoparticles as particulate labels. In addition we strived to verify the common assumption of the photostability of up-converting phosphor particles supporting their potential applicability in imaging. Detection limits in two-site immunoassay for free prostate-specific antigen (free-PSA) were 0.53 ng L -1 and 1.3 ng L -1 using two different up-converting phosphors and 0.16 ng L -1 using europium(III) nanoparticle. Large size distribution and non-specific binding of up-converting phosphor particles caused assay variation in low analyte concentrations and limited the analytical detection limit. The non-specific binding was the major factor limiting the analytical sensitivity of the immunoassay. The results suggests the need for nanoscaled and uniformely sized UCP-particles to increace the sensitivity and applicability of up-converting phosphor particles. Anti-Stokes photoluminescence of up-converting phosphor particles did not photobleach when measured repeatedly, on the contrary, the time-resolved fluorescence of europium nanoparticles photobleached relatively rapidly

An open-label pilot trial of alpha-lipoic acid for weight loss in patients with schizophrenia without diabetes.

Science.gov (United States)

Ratliff, Joseph C; Palmese, Laura B; Reutenauer, Erin L; Tek, Cenk

2015-01-01

A possible mechanism of antipsychotic-induced weight gain is activation of hypothalamic monophosphate-dependent kinase (AMPK) mediated by histamine 1 receptors. Alpha-lipoic acid (ALA), a potent antioxidant, counteracts this effect and may be helpful in reducing weight for patients taking antipsychotics. The objective of this open-label study was to assess the efficacy of ALA (1,200 mg) on twelve non-diabetic schizophrenia patients over ten weeks. Participants lost significant weight during the intervention (-2.2 kg±2.5 kg). ALA was well tolerated and was particularly effective for individuals taking strongly antihistaminic antipsychotics (-2.9 kg±2.6 kg vs. -0.5 kg±1.0 kg). NCT01355952.

Relative oral bioavailability of morphine and naltrexone derived from crushed morphine sulfate and naltrexone hydrochloride extended-release capsules versus intact product and versus naltrexone solution: a single-dose, randomized-sequence, open-label, three-way crossover trial in healthy volunteers.

Science.gov (United States)

Johnson, Franklin K; Stark, Jeffrey G; Bieberdorf, Frederick A; Stauffer, Joe

2010-06-01

Morphine sulfate/sequestered naltrexone hydrochloride (HCl) (MS-sNT) extended-release fixed-dose combination capsules, approved by the US Food and Drug Administration (FDA) in August 2009 for chronic moderate to severe pain, contain extended-release morphine pellets with a sequestered core of the opioid antagonist naltrexone. MS-sNT was designed so that if the product is tampered with by crushing, the naltrexone becomes bioavailable to mitigate morphine-induced subjective effects, rendering the product less attractive for tampering. The primary aim of this study was to compare the oral bioavailability of naltrexone and its metabolite 6-beta-naltrexol, derived from crushed pellets from MS-sNT capsules, to naltrexone solution. This study also assessed the relative bioavailability of morphine from crushed pellets from MS-sNT capsules and that from the whole, intact product. This single-dose, randomized-sequence, open-label, 3-period, 3-treatment crossover trial was conducted in healthy volunteers. Adults admitted to the study center underwent a 10-hour overnight fast before study drug administration. Each subject received all 3 of the following treatments, 1 per session, separated by a 14-day washout: tampered pellets (crushed for >or=2 minutes with a mortar and pestle) from a 60-mg MS-sNT capsule (60 mg morphine/2.4 mg naltrexone); 60-mg whole, intact MS-sNT capsule; and oral naltrexone HCl (2.4 mg) solution. Plasma concentrations of naltrexone and 6-beta-naltrexol were measured 0 to 168 hours after administration. Morphine pharmaco-kinetics of crushed and whole pellets were determined 0 to 72 hours after administration. The analysis of relative bioavailability was based on conventional FDA criteria for assuming bioequivalence; that is, 90% CIs for ratios of geometric means (natural logarithm [In]-transformed C(max) and AUC) fell within the range of 80% to 125%. Subjects underwent physical examinations, clinical laboratory tests, and ECG at screening and study

Eggshell membrane: A possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies

Directory of Open Access Journals (Sweden)

Kevin J Ruff

2009-05-01

Full Text Available Kevin J Ruff1, Dale P DeVore2, Michael D Leu3, Mark A Robinson41ESM Technologies, LLC, Carthage, MO, USA; 2Membrell, LLC, Carthage, MO, USA; 3Private Practice, Jenks, OK, USA; 4Robinson Family Health Center, Carthage, MO, USABackground: Natural Eggshell Membrane (NEM® is a novel dietary supplement that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy joint and connective tissues. Two single center, open-label human clinical studies were conducted to evaluate the efficacy and safety of NEM® as a treatment for pain and inflexibility associated with joint and connective tissue disorders. Methods: Eleven (single-arm trial and 28 (double-arm trial patients received oral NEM® 500 mg once daily for four weeks. The primary outcome measure was to evaluate the change in general pain associated with the treatment joints/areas (both studies. In the single-arm trial, range of motion (ROM and related ROM-associated pain was also evaluated. The primary treatment response endpoints were at seven and 30 days. Both clinical assessments were performed on the intent-to-treat (ITT population within each study.Results: Single-arm trial: Supplementation with NEM® produced a significant treatment response at seven days for flexibility (27.8% increase; P = 0.038 and at 30 days for general pain (72.5% reduction; P = 0.007, flexibility (43.7% increase; P = 0.006, and ROM-associated pain (75.9% reduction; P = 0.021. Double-arm trial: Supplementation with NEM® produced a significant treatment response for pain at seven days for both treatment arms (X: 18.4% reduction; P = 0.021. Y: 31.3% reduction; P = 0.014. There was no clinically meaningful difference between treatment arms at seven days, so the Y arm crossed over to the X formulation for the remainder of the study. The significant treatment response continued through 30 days for pain (30.2% reduction; P = 0.0001. There were no adverse events reported during either

No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a Phase I Open Label Study to assess safety, tolerability and cytokine responses

Science.gov (United States)

Although Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed since the mid 1990s by between 2 and 5 million people daily, the scientific literature lacks rigorous clinical trials that describe the potential harms of LGG, particularly in the elderly. The primary objective of this open label...

Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial.

Science.gov (United States)

Smith, Deidre J; Sarris, Jerome; Dowling, Nathan; O'Connor, Manjula; Ng, Chee H

2018-04-01

Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD). A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted. Primary outcomes of depression, clinical severity, and daytime sleepiness were measured. After 8 weeks, 54% of patients had a ≥50% reduction on the HAM-D, and 45% were in remission (HAM-D ≤ 7). The eta-squared statistic (0.59) indicated a large effect size for the reduction of depression (equivalent to Cohen's d of 2.4). However confidence in this effect size is tempered due to the lack of a placebo. The mean score for the Clinical Global Impression Severity Scale was significantly improved by 1.28 points (P depression.

Phase II open label study of valproic acid in spinal muscular atrophy.

Directory of Open Access Journals (Sweden)

Kathryn J Swoboda

Full Text Available Preliminary in vitro and in vivo studies with valproic acid (VPA in cell lines and patients with spinal muscular atrophy (SMA demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS, electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP amplitudes and motor unit number estimation (MUNE, body composition and bone density via dual-energy X-ray absorptiometry (DEXA, and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p

Should we use closed or open infusion containers for prevention of bloodstream infections?

Science.gov (United States)

Rangel-Frausto, Manuel S; Higuera-Ramirez, Francisco; Martinez-Soto, Jose; Rosenthal, Victor D

2010-02-02

Hospitalized patients in critical care settings are at risk for bloodstream infections (BSI). Most BSIs originate from a central line (CL), and they increase length of stay, cost, and mortality. Open infusion containers may increase the risk of contamination and administration-related (CLAB) because they allow the entry of air into the system, thereby also providing an opportunity for microbial entry. Closed infusion containers were designed to overcome this flaw. However, open infusion containers are still widely used throughout the world.The objective of the study was to determine the effect of switching from open (glass, burettes, and semi-rigid) infusion containers to closed, fully collapsible, plastic infusion containers (Viaflex) on the rate and time to onset of central line-associated bloodstream infections CLABs. An open label, prospective cohort, active healthcare-associated infection surveillance, sequential study was conducted in four ICUs in Mexico. Centers for Disease Control National Nosocomial Infections Surveillance Systems definitions were used to define device-associated infections. A total of 1,096 adult patients who had a central line in place for >24 hours were enrolled. The CLAB rate was significantly higher during the open versus the closed container period (16.1 versus 3.2 CLAB/1000 central line days; RR = 0.20, 95% CI = 0.11-0.36, P container period (1.4% Days 2-4 to 0.5% Days 8-10), but increased in the open container period (4.9% Days 2-4 to 5.4% Days 8-10). The chance of acquiring a CLAB was significantly decreased (81%) in the closed container period (Cox proportional hazard ratio 0.19, P container period (23.4% versus 16.1%; RR = 0.69, 95% CI = 0.54-0.88, P containers significantly reduced CLAB rate, the probability of acquiring CLAB, and mortality.

Augmentation of light therapy in difficult-to-treat depressed patients: an open-label trial in both unipolar and bipolar patients

Science.gov (United States)

Camardese, Giovanni; Leone, Beniamino; Serrani, Riccardo; Walstra, Coco; Di Nicola, Marco; Della Marca, Giacomo; Bria, Pietro; Janiri, Luigi

2015-01-01

Objectives We investigated the clinical benefits of bright light therapy (BLT) as an adjunct treatment to ongoing psychopharmacotherapy, both in unipolar and bipolar difficult-to-treat depressed (DTD) outpatients. Methods In an open-label study, 31 depressed outpatients (16 unipolar and 15 bipolar) were included to undergo 3 weeks of BLT. Twenty-five completed the treatment and 5-week follow-up. Main outcome measures Clinical outcomes were evaluated by the Hamilton Depression Rating Scale (HDRS). The Snaith–Hamilton Pleasure Scale and the Depression Retardation Rating Scale were used to assess changes in anhedonia and psychomotor retardation, respectively. Results The adjunctive BLT seemed to influence the course of the depressive episode, and a statistically significant reduction in HDRS scores was reported since the first week of therapy. The treatment was well-tolerated, and no patients presented clinical signs of (hypo)manic switch during the overall treatment period. At the end of the study (after 5 weeks from BLT discontinuation), nine patients (36%, eight unipolar and one bipolar) still showed a treatment response. BLT augmentation also led to a significant improvement of psychomotor retardation. Conclusion BLT combined with the ongoing pharmacological treatment offers a simple approach, and it might be effective in rapidly ameliorating depressive core symptoms of vulnerable DTD outpatients. These preliminary results need to be confirmed in placebo-controlled, randomized, double-blind clinical trial on larger samples. PMID:26396517

Multi-criteria decision making with linguistic labels: a comparison of two methodologies applied to energy planning

OpenAIRE

Afsordegan, Arayeh; Sánchez Soler, Monica; Agell Jané, Núria; Cremades Oliver, Lázaro Vicente; Zahedi, Siamak

2014-01-01

This paper compares two multi-criteria decision making (MCDM) approaches based on linguistic label assessment. The first approach consists of a modified fuzzy TOPSIS methodology introduced by Kaya and Kahraman in 2011. The second approach, introduced by Agell et al. in 2012, is based on qualitative reasoning techniques for ranking multi-attribute alternatives in group decision-making with linguistic labels. Both approaches are applied to a case of assessment and selection of the most suita...

Randomized Crossover Comparison of the Short-Term Efficacy and Safety of Single Half-Dose Silodosin and Tamsulosin Hydrochoride in Men With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

Science.gov (United States)

Takeshita, Hideki; Moriyama, Shingo; Arai, Yoshiaki; Washino, Satoshi; Saito, Kimitoshi; Chiba, Koji; Horiuchi, Susumu; Noro, Akira

2016-01-01

To compare the efficacy and safety of single half-dose silodosin and single full-dose tamsulosin in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Japanese men aged ≥50 years with LUTS/BPH and an International Prostate Symptom Score (IPSS) of ≥8 were enrolled in the randomized crossover study and divided into silodosin-preceding (S-T) and tamsulosin-preceding (T-S) groups. The S-T group received 4 mg silodosin once daily for 4 weeks followed by 0.2 mg tamsulosin once daily for 4 weeks. The T-S group received the reverse treatment sequence. A washout period prior to drug crossover was not included. Subjective and objective efficacy parameters including IPSS, quality of life (QOL) index, uroflowmetry, and safety were compared between the two groups. Thirty of 34 men (S-T group n = 16; T-S group n = 14) completed the study. Both drugs significantly improved all IPSS items and QOL index in the first treatment period. Subjective improvement in nocturia by silodosin was observed in both the first and crossover treatment periods. Objective improvement in maximum flow rate by silodosin was only observed in the first treatment period. Adverse events occurred more frequently with silodosin than with tamsulosin; however, none of the adverse events required treatment discontinuation. Ejaculation disorders occurred in three participants (10%) and were associated with silodosin use. Single half-dose silodosin has a similar efficacy to full-dose tamsulosin in Japanese men with LUTS/BPH and thus, may represent an effective, safe, and affordable treatment option. © 2015 Wiley Publishing Asia Pty Ltd.

A Randomized Study Comparing Outcomes of Stapled and Hand-Sutured Anastomoses in Patients Undergoing Open Gastrointestinal Surgery

OpenAIRE

Chandramohan, S. M.; Gajbhiye, Raj Narenda; Agwarwal, Anil; Creedon, Erin; Schwiers, Michael L.; Waggoner, Jason R.; Tatla, Daljit

2012-01-01

Although stapling is an alternative to hand-suturing in gastrointestinal surgery, recent trials specifically designed to evaluate differences between the two in surgery time, anastomosis time, and return to bowel activity are lacking. This trial compared the outcomes of the two in subjects undergoing open gastrointestinal surgery. Adult subjects undergoing emergency or elective surgery requiring a single gastric, small, or large bowel anastomosis were enrolled into this open-label, prospectiv...

An Intervention with Mineral Water Decreases Cardiometabolic Risk Biomarkers. A Crossover, Randomised, Controlled Trial with Two Mineral Waters in Moderately Hypercholesterolaemic Adults

Directory of Open Access Journals (Sweden)

Laura Toxqui

2016-06-01

Full Text Available Water intake is essential for health maintenance and disease prevention. The effects of an intervention with two mineral waters, sodium-bicarbonated mineral water (BW or control mineral water low in mineral content (CW, on cardiometabolic risk biomarkers were studied. In a randomised-controlled crossover-trial, sixty-four moderately hypercholesterolaemic adults were randomly assigned to consume 1 L/day of either BW (sodium, 1 g/L; bicarbonate, 2 g/L or CW with the main meals for eight weeks, separated by an eight-week washout period. Blood lipids, lipid oxidation, glucose, insulin, aldosterone, urine pH, urinary electrolytes, blood pressure, body weight, fluid intake, energy, and nutrients from total diet and beverages were determined. Total cholesterol, LDL cholesterol, and glucose decreased (p < 0.01, oxidised LDL tended to decrease (p = 0.073, and apolipoprotein B increased during the intervention, without water type effect. Energy and carbohydrates from beverages decreased since soft drinks and fruit juice consumptions decreased throughout the trial. BW increased urinary pH (p = 0.006 and reduced calcium/creatinine excretion (p = 0.011. Urinary potassium/creatinine decreased with both waters. Consumption of 1 L/day of mineral water with the main meals reduces cardiometabolic risk biomarkers, likely to be attributed to a replacement of soft drinks by water. In addition, BW does not affect blood pressure and exerts a moderate alkalizing effect in the body.

An open-label extension study of the safety and efficacy of risperidone in children and adolescents with autistic disorder.

Science.gov (United States)

Kent, Justine M; Hough, David; Singh, Jaskaran; Karcher, Keith; Pandina, Gahan

2013-12-01

The purpose of this study was to evaluate the long-term safety and efficacy of risperidone in treating irritability and related behaviors in children and adolescents with autistic disorders. In this 6 month (26 week) open-label extension (OLE) study, patients (5-17 years of age, who completed the previous fixed-dose, 6 week, double-blind [DB] phase) were flexibly dosed with risperidone based on body weight. The maximum allowed dose was 1.25 mg/day for those weighing 20 to autistic, psychiatric, and behavioral disorders. Patients experienced some additional improvement in irritability and related behaviors. This phase-4 study is registered at ClinicalTrials.gov (NCT00576732).

A randomized two-way crossover comparative pharmacokinetic study of two different tablet formulations containing ilaprazole in healthy human Indian volunteers

Directory of Open Access Journals (Sweden)

Shubhasis Dan

2014-01-01

Full Text Available Background: Proton Pump Inhibitors (PPI are observed to be great healer in gastroesophageal reflux disorder (GERD and duodenal ulcer. Quantification of the drugs in human plasma by validated bioanalytical method are very important to determine pharmacokinetic parameters for undergoing comparative study with standard available formulations to make the newer one commercially available. Objective: The objective of this study was to determine the relative bioavailability of Ilaprazole, a novel PPI comparing the test formulation to the reference one according to standard regulatory guidelines. Materials and Methods: The bioequivalence of two tablet formulations, one as reference and other as test containing 10 mg of ilaprazole [CAS No. 172152-36-2] was studied in 12 healthy Indian volunteers. This was a single dose, twoperiod and randomized crossover study separated with a washout period of one week. Plasma samples for pharmacokinetic analysis were collected before dosing and at pre-specified time points after dosing. The concentration of ilaprazole in plasma was determined by a validated HPLC-UV method using theophylline as internal standard. The formulations were compared using the parameters Area under the plasma concentration-time curve (AUC 0-t , Area under the plasma concentration-time curve from zero to infinity (AUC 0-͵, Peak plasma concentration (C max , and time to reach peak plasma concentration (t max . Results: Mean AUC 0-t of test and reference product were calculated to be 2627.793 ± 154.989 ng h ml−1 and 2555.905 ± 225.916 ng h ml−1 , with a C max of 347.459 ± 48.175 ng h ml−1 . While mean AUC 0-͵ of test and reference product were calculated to be 2733.334 ± 242.438 ng h ml−1 and 2728.716 ± 284.408 ng h ml−1 . Conclusion: The results of this investigation indicated no statistically significant differences between the logarithmic transformed AUC 0-͵ and C max values of the two preparations. The 90% confidence

Case-crossover study of Burkholderia cepacia complex bloodstream infection associated with contaminated intravenous bromopride.

Science.gov (United States)

Martins, Ianick Souto; Pellegrino, Flávia Lúcia Piffano Costa; Freitas, Andrea d'Avila; Santos, Marisa da Silva; Ferraiuoli, Giovanna Ianini d'Alemeida; Vasques, Márcia Regina Guimarães; Amorim, Efigenia Lourdes Teixeira; Oliveira, Sandra; Nouér, Simone Aranha; Cardoso, Fernando Luiz Lopes; Mascarenhas, Luiz Affonso; Magalhães, Ana Cristina Gouveia; Cleinman, Isabella Barbosa; Figueiredo, Agnes Marie Sá; Moreira, Beatriz Meurer

2010-05-01

To investigate an outbreak of healthcare-associated Burkholderia cepacia complex (BCC) primary bloodstream infections (BCC-BSI). Case-crossover study in a public hospital, a university hospital and a private hospital in Rio de Janeiro, Brazil, from March 2006 to May 2006. Twenty-five patients with BCC-BSI. After determining the date BCC-BSI symptoms started for each patient, 3 time intervals of data collection were defined, each one with a duration of 3 days: the case period, starting just before BCC-BSI symptoms onset; the control period, starting 6 days before BCC-BSI symptoms onset; and the washout period, comprising the 3 days between the case period and the control period. Exposures evaluated were intravascular solutions and invasive devices and procedures. Potential risk factors were identified by using the McNemar chi(2) adjusted test. Cultures of samples of potentially contaminated solutions were performed. BCC strain typing was performed by pulsed-field gel electrophoresis using SpeI. The statistical analysis revealed that the use of bromopride and dipyrone was associated with BCC-BSI. A total of 21 clinical isolates from 17 (68%) of the 25 patients and an isolate obtained from the bromopride vial were available for strain typing. Six pulsotypes were detected. A predominant pulsotype (A) accounted for 11 isolates obtained from 11 patients (65%) in the 3 study hospitals. Our investigation, using a case-crossover design, of an outbreak of BCC-BSI infections concluded it was polyclonal but likely caused by infusion of contaminated bromopride. The epidemiological finding was validated by microbiological analysis. After recall of contaminated bromopride vials by the manufacturer, the outbreak was controlled.

Examination of the evidence for off-label use of gabapentin.

Science.gov (United States)

Mack, Alicia

2003-01-01

(1) Describe the relevance of off-label use of gabapentin to managed care pharmacy; (2) summarize recent FDA warnings and media reports related to off-label gabapentin use; (3) review medical information pertaining to the off-label use of gabapentin; (4) outline alternatives to off-label use of gabapentin in an evidence-based fashion, where literature exists to support such alternatives; and (5) encourage key clinicians and decision makers in managed care pharmacy to develop and support programs that restrict the use of gabapentin to specific evidence-based situations. Gabapentin is approved by the U.S. Food and Drug Administration (FDA) for adjunctive therapy in treatment of partial seizures and postherpetic neuralgia. Various off-label (unapproved) uses have been reported, and the use of gabapentin for off-label purposes has reportedly exceeded use for FDAapproved indications. Pharmaceutical marketing practices and physician dissatisfaction with currently available pharmacological treatment options may be key factors that contribute to this prescribing trend. Recently, the media has focused on these issues, noting that many cases of reported safety and effectiveness of gabapentin for off-label use may have been fabricated. A thorough review of the medical and pharmacy literature related to off-label use of gabapentin was performed, and a summary of the literature for the following conditions is presented: bipolar disorder, peripheral neuropathy, diabetic neuropathy, complex regional pain syndrome, attention deficit disorder, restless legs syndrome, trigeminal neuralgia, periodic limb movement disorder of sleep, migraine headaches, and alcohol withdrawal syndrome. A common theme in the medical literature for gabapentin is the prevalence of open-label studies and a lack of randomized controlled clinical trials for all but a small number of indications. In the majority of circumstances where it has reported potential for.off-label. use, gabapentin is not the optimal

Effect of consuming a purple-fleshed sweet potato beverage on health-related biomarkers and safety parameters in Caucasian subjects with elevated levels of blood pressure and liver function biomarkers: a 4-week, open-label, non-comparative trial.

Science.gov (United States)

Oki, Tomoyuki; Kano, Mitsuyoshi; Watanabe, Osamu; Goto, Kazuhisa; Boelsma, Esther; Ishikawa, Fumiyasu; Suda, Ikuo

2016-01-01

An open-label study with one treatment arm was conducted to investigate changes in health-related biomarkers (blood pressure and liver enzyme activity) and the safety of 4 weeks of consuming a purple-fleshed sweet potato beverage in Caucasian subjects. Twenty healthy adults, 18-70 years of age, with a body mass index >25 kg/m(2), elevated blood pressure and elevated levels of liver function biomarkers consumed two cartons of purple-fleshed sweet potato beverage (125 ml, including 117 mg anthocyanin per carton) daily for 4 weeks. Hematology, serum clinical profile, dipstick urinalysis and blood pressure were determined before consumption, at 2 and 4 weeks of consumption and after a 2-week washout period. A trend was found toward lowering systolic blood pressure during the treatment period (p=0.0590). No significant changes were found in diastolic blood pressure throughout the study period. Systolic blood pressure was significantly lower after 4 weeks of consumption compared with before consumption (p=0.0125) and was significantly higher after the 2-week washout period compared with after consumption (p=0.0496). The serum alanine aminotransferase level significantly increased over time, but aspartate aminotransferase and γ-glutamyltransferase levels stayed within the normal range of reference values. Safety parameters of the blood and urine showed no clinically relevant changes. The consumption of a purple-fleshed sweet potato beverage for 4 weeks resulted in no clinically relevant changes in safety parameters of the blood and urine and showed a trend toward lowering systolic blood pressure.

Stress analysis of LOFT steam generator blowdown cross-over line

International Nuclear Information System (INIS)

Singh, J.N.

1978-01-01

The purpose of this report is to demonstrate compliance of the LOFT Steam Generator Blowdown Cross-Over Piping with the ASME Boiler and Pressure Vessel Code, Section III, Subsection NC. Deadweight, thermal expansion, seismic, LOCE, and LOCA loads have been considered. With the addition of two snubbers, as shown in this report, the system conforms to all requirements

Open-label taste-testing study to evaluate the acceptability of both strawberry-flavored and orange-flavored amylmetacresol/2,4-dichlorobenzyl alcohol throat lozenges in healthy children.

Science.gov (United States)

Thompson, Alex; Reader, Sandie; Field, Emma; Shephard, Adrian

2013-06-01

Acute sore throat (pharyngitis) is one of the most common illnesses for which children are seen by primary care physicians. Most cases are caused by viruses and are benign and self-limiting. Clinically proven, over-the-counter throat lozenges provide rapid and effective relief of acute sore throat symptoms, and are increasingly important in self-management of this condition. The purpose of this study (International Standard Randomized Controlled Trial Number: ISRCTN34958871) was to evaluate the acceptability of two licensed, commercially available sore throat lozenges containing amylmetacresol and 2,4-dichlorobenzyl (AMC/DCBA)--one strawberry flavored and the other orange flavored--in healthy children. This was an open-label, single-dose, crossover, taste-testing study in children recruited via a clinical database and advertisements over a 3.5-week period. Potentially eligible participants were invited to attend the taste-testing session at a clinic. At the screening session, which took place either before or on the day of taste testing, details of relevant medical history, medication, and demographics were recorded. Of the 108 screened subjects, 102 were recruited. These were healthy male and female children aged 6-12 years. Each child cleansed their palate with water and water biscuits before tasting a strawberry-flavored lozenge (Strepsils® strawberry sugar free, Reckitt Benckiser Healthcare Limited, Nottingham, UK; PL 00063/0395), which was sucked for 1 minute and then expelled. The orange-flavored lozenge (Strepsils® orange with vitamin C, Reckitt Benckiser Healthcare Limited, Nottingham, UK; PL 016242152) was tasted at least 15 minutes later following further cleansing of the palate. The spontaneous reaction of the child on tasting each lozenge was observed and recorded. Subjects were asked to indicate their liking for each lozenge, using a 7-point hedonic facial scale, and were required to answer a series of questions relating to what they liked and

Role of superconducting energy gap in extended BCS-Bose crossover theory

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Chávez, I.; García, L. A.; de Llano, M.; Grether, M.

2017-10-01

The generalized Bose-Einstein condensation (GBEC) theory of superconductivity (SC) is briefly surveyed. It hinges on three distinct new ingredients: (i) Treatment of Cooper pairs (CPs) as actual bosons since they obey Bose statistics, in contrast to BCS pairs which do not obey Bose commutation relations; (ii) inclusion of two-hole Cooper pairs (2hCPs) on an equal footing with two-electron Cooper pairs (2eCPs), thus making this a complete boson-fermion (BF) model; and (iii) inclusion in the resulting ternary ideal BF gas with particular BF vertex interactions that drive boson formation/disintegration processes. GBEC subsumes as special cases both BCS (having its 50-50 symmetry of both kinds of CPs) and ordinary BEC theories (having no 2hCPs), as well as the now familiar BCS-Bose crossover theory. We extended the crossover theory with the explicit inclusion of 2hCPs and construct a phase diagram of Tc/TF versus n/nf, where Tc and TF are the critical and Fermi temperatures, n is the total number density and nf that of unbound electrons at T = 0. Also, with this extended crossover one can construct the energy gap Δ(T)/Δ(0) versus T/Tc for some elemental SCs by solving at least two equations numerically: a gap-like and a number equation. In 50-50 symmetry, the energy gap curve agrees quite well with experimental data. But ignoring 2hCPs altogether leads to the gap curve falling substantially below that with 50-50 symmetry which already fits the data quite well, showing that 2hCPs are indispensable to describe SCs.

An Open-Label, Phase 1 Study to Assess the Effects of Hepatic Impairment on Pomalidomide Pharmacokinetics.

Science.gov (United States)

Li, Yan; Wang, Xiaomin; Liu, Liangang; Zhang, Chengyue; Gomez, Diana; Reyes, Josephine; Palmisano, Maria; Zhou, Simon

2018-05-10

Pomalidomide is an immunomodulatory drug and the dosage of 4 mg per day taken orally on days 1-21 of repeated 28-day cycles has been approved in the European Union and United States to treat patients with relapsed/refractory multiple myeloma. Because pomalidomide is extensively metabolized prior to excretion, a total of 32 subjects (8 healthy subjects in group 1; 8 subjects with severe hepatic impairment in group 2; 8 subjects with moderate hepatic impairment in group 3; and 8 subjects with mild hepatic impairment in group 4) were enrolled in a multicenter, open-label, single-dose study to assess the impact of hepatic impairment on pomalidomide exposure. Following administration of a single oral dose of 4-mg pomalidomide, the geometric mean ratios of pomalidomide total plasma exposures (AUC) were 171.5%, 157.5%, and 151.2% and the geometric mean ratios of pomalidomide plasma peak exposures (C max ) were 75.8%, 94.8%, and 94.2% for subjects with severe, moderate, or mild hepatic impairment, respectively, versus healthy subjects. Pomalidomide administered as a single oral 4-mg dose was safe and well tolerated by healthy subjects and subjects with severe, moderate, or mild hepatic impairment. Based on the pharmacokinetic results from this study, the pomalidomide prescribing information approved by the US Food and Drug Administration recommends for patients with mild or moderate hepatic impairment (Child-Pugh classes A or B), a 3-mg starting daily dose (25% dose reduction) and for patients with severe hepatic impairment (Child-Pugh class C), a 2-mg starting daily dose (50% dose reduction). © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Opening complete band gaps in two dimensional locally resonant phononic crystals

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Zhou, Xiaoling; Wang, Longqi

2018-05-01

Locally resonant phononic crystals (LRPCs) which have low frequency band gaps attract a growing attention in both scientific and engineering field recently. Wide complete locally resonant band gaps are the goal for researchers. In this paper, complete band gaps are achieved by carefully designing the geometrical properties of the inclusions in two dimensional LRPCs. The band structures and mechanisms of different types of models are investigated by the finite element method. The translational vibration patterns in both the in-plane and out-of-plane directions contribute to the full band gaps. The frequency response of the finite periodic structures demonstrate the attenuation effects in the complete band gaps. Moreover, it is found that the complete band gaps can be further widened and lowered by increasing the height of the inclusions. The tunable properties by changing the geometrical parameters provide a good way to open wide locally resonant band gaps.

Effects of rasagiline on freezing of gait in Parkinson's disease - an open-label, multicenter study.

Science.gov (United States)

Cibulcik, Frantisek; Benetin, Jan; Kurca, Egon; Grofik, Milan; Dvorak, Miloslav; Richter, Denis; Donath, Vladimir; Kothaj, Jan; Minar, Michal; Valkovic, Peter

2016-12-01

Freezing of gait is a disabling symptom in advanced Parkinson's disease. Positive effects have been suggested with MAO-B inhibitors. We report on an open label clinical study on the efficacy of rasagiline as add-on therapy on freezing of gait and quality of life in patients with Parkinson's disease. Forty two patients with freezing of gait were treated with 1 mg rasagiline daily as an add-on therapy. Patients were assessed at baseline and after 1, 2 and 3 months of treatment. Freezing of gait severity was assessed using the Freezing of Gait Questionnaire, motor impairment by the modified MDS UPDRS part III, and quality of life using the PDQ-39 questionnaire. Patients treated with rasagiline had a statistically significant decrease in FoG-Q score and modified MDS UPDRS score after 1, 2 and 3 months of therapy. A moderately strong (r = 0.686, P = 0.002) correlation between the effects on mobility and freezing of gait was found. We also observed a statistically significant improvement in global QoL and in the subscales mobility, ADL, stigma and bodily discomfort in patients after 3 months of rasagiline therapy. A significant correlation (r = 0.570, P = 0.02) between baseline FoG-Q score and the baseline score for the PDQ Mobility subscale was found. In our study rasagiline as add-on antiparkinsonian therapy significantly improved mobility, freezing of gait and quality of life. The positive effect on freezing of gait appears to be related to improvement of mobility.

Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial

NARCIS (Netherlands)

Marina, Neyssa M.; Smeland, Sigbjørn; Bielack, Stefan S.; Bernstein, Mark; Jovic, Gordana; Krailo, Mark D.; Hook, Jane M.; Arndt, Carola; van den Berg, Henk; Brennan, Bernadette; Brichard, Bénédicte; Brown, Ken L. B.; Butterfass-Bahloul, Trude; Calaminus, Gabriele; Daldrup-Link, Heike E.; Eriksson, Mikael; Gebhardt, Mark C.; Gelderblom, Hans; Gerss, Joachim; Goldsby, Robert; Goorin, Allen; Gorlick, Richard; Grier, Holcombe E.; Hale, Juliet P.; Hall, Kirsten Sundby; Hardes, Jendrik; Hawkins, Douglas S.; Helmke, Knut; Hogendoorn, Pancras C. W.; Isakoff, Michael S.; Janeway, Katherine A.; Jürgens, Heribert; Kager, Leo; Kühne, Thomas; Lau, Ching C.; Leavey, Patrick J.; Lessnick, Stephen L.; Mascarenhas, Leo; Meyers, Paul A.; Mottl, Hubert; Nathrath, Michaela; Papai, Zsuzsanna; Randall, R. Lor; Reichardt, Peter; Renard, Marleen; Safwat, Akmal Ahmed; Schwartz, Cindy L.; Stevens, Michael C. G.; Strauss, Sandra J.; Teot, Lisa; Werner, Mathias; Sydes, Matthew R.; Whelan, Jeremy S.

2016-01-01

We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. EURAMOS-1 was an open-label,

Novel Optical Labeling Scheme for Ultra-High Bit Rate Data Packets

DEFF Research Database (Denmark)

Medhin, Ashenafi Kiros; Galili, Michael; Oxenløwe, Leif Katsuo

2013-01-01

We propose and verify by simulations an optical in-band labeling scheme for ultra-fast optical switching. The scheme is able to label more than 60 different 640-Gbit/s OTDM packets with eye opening penalty <1 dB....

Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

Science.gov (United States)

Liu, Dongzhou J; Collaku, Agron

2018-01-01

Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

Distance labeling schemes for trees

DEFF Research Database (Denmark)

Alstrup, Stephen; Gørtz, Inge Li; Bistrup Halvorsen, Esben

2016-01-01

We consider distance labeling schemes for trees: given a tree with n nodes, label the nodes with binary strings such that, given the labels of any two nodes, one can determine, by looking only at the labels, the distance in the tree between the two nodes. A lower bound by Gavoille et al. [Gavoille...... variants such as, for example, small distances in trees [Alstrup et al., SODA, 2003]. We improve the known upper and lower bounds of exact distance labeling by showing that 1/4 log2(n) bits are needed and that 1/2 log2(n) bits are sufficient. We also give (1 + ε)-stretch labeling schemes using Theta...

Cross-Over Clinical Trials?

Directory of Open Access Journals (Sweden)

Latif Gachkar

2017-01-01

Full Text Available Abstract Cross-Over Clinical Trials in comparison with Parallel groups clinical trials have some advantages such as control of confounding variables, small sample size, and short time to implement the research project. But this type of research has few essential limitations that discusses in this monogram.

111In-labeled platelet scintigraphy and two-dimensional echocardiography for detection of left atrial appendage thrombi. Studies in a new canine model

International Nuclear Information System (INIS)

Vandenberg, B.F.; Seabold, J.E.; Conrad, G.R.; Kieso, R.; Johnson, J.; Fox-Eastham, K.; Ponto, J.; Bruch, P.; Kerber, R.E.

1988-01-01

111In-labeled platelet scintigraphy and two-dimensional echocardiography were performed in 40 dogs to determine the ability of the two techniques to detect left atrial appendage thrombi. Thrombi were induced in 33 dogs that were classified into two groups, acute or chronic, according to the time of labeled-platelet injection after thrombus induction. In the acute group (17 dogs), platelets were injected 24 hours after thrombus induction. In the chronic group (16 dogs), platelets were injected 4-8 days after thrombus induction. Sham thoracotomies were performed on seven additional control dogs who did not receive thrombin injections. Analog and blood pool-corrected 111In-labeled platelet scintigraphy images were obtained 4-72 hours later. Closed-chest two-dimensional echocardiography was performed before thoracotomy and repeated at the time of scintigraphy. The location and size of each thrombus were verified at autopsy. Two-dimensional echocardiography detected three of 17 acute (mean volume, 1.2 +/- 1.0 cc) and three of 10 chronic (mean volume, 0.4 +/- 0.3 cc; p less than 0.025) left atrial appendage thrombi. 111In-labeled platelet scintigraphy detected all 17 acute thrombi but only two of 10 chronic thrombi. The measured radioactivity levels of the excised thrombi were 1,949 +/- 1,665 cpm/clot/dose in group 1 and 228 +/- 213 cpm/clot/dose in group 2 (p less than 0.005). In this model, 111In-labeled platelet scintigraphy was able to detect acute left atrial appendage thrombi that could not be identified by two-dimensional echocardiography. Both techniques showed poor sensitivity for detection of chronic thrombi. The decline in sensitivity of 111In-labeled platelet scintigraphy for detection of older thrombi is probably due to diminished labeled-platelet incorporation

Comparative study of fixation of Co57 labelled bleomycin, labelled gallium citrate and Hg197 labelled mercury chloride, benign or malignant pulmonary lesions

International Nuclear Information System (INIS)

Bertrand, A.; Vaillant, G.; Robert, J.; Vaillant, D.; Nouel, J.P.; Delorme, J.; Lamy, P.

1975-01-01

Over the last ten years, numerous labelled molecules have been used in lung diseases, in order to attempt definite localisation of primary or secondary carcinoma. Three of these substances are now used: cobalt 57-labelled bleomycin, Hg 197 Cl 2 and Ga 67 citrate. A study of 34 patient with malignant or tuberculous lung disease with definite diagnosis, permitted demonstration of the fact that the highest uptake, or the best images, were obtained with labelled bleomycin. However, the long period of Co 57 limits its indications in young subjects and, in these cases, HgCl 2 is indicated [fr

Bloom syndrome helicase in meiosis: Pro-crossover functions of an anti-crossover protein.

Science.gov (United States)

Hatkevich, Talia; Sekelsky, Jeff

2017-09-01

The functions of the Bloom syndrome helicase (BLM) and its orthologs are well characterized in mitotic DNA damage repair, but their roles within the context of meiotic recombination are less clear. In meiotic recombination, multiple repair pathways are used to repair meiotic DSBs, and current studies suggest that BLM may regulate the use of these pathways. Based on literature from Saccharomyces cerevisiae, Arabidopsis thaliana, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans, we present a unified model for a critical meiotic role of BLM and its orthologs. In this model, BLM and its orthologs utilize helicase activity to regulate the use of various pathways in meiotic recombination by continuously disassembling recombination intermediates. This unwinding activity provides the meiotic program with a steady pool of early recombination substrates, increasing the probability for a DSB to be processed by the appropriate pathway. As a result of BLM activity, crossovers are properly placed throughout the genome, promoting proper chromosomal disjunction at the end of meiosis. This unified model can be used to further refine the complex role of BLM and its orthologs in meiotic recombination. © 2017 WILEY Periodicals, Inc.

Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study

Directory of Open Access Journals (Sweden)

Sasaki T

2014-01-01

Full Text Available Tsuyoshi Sasaki,1,2 Kenji Hashimoto,3 Masumi Tachibana,1 Tsutomu Kurata,1 Keiko Okawada,1 Maki Ishikawa,1 Hiroshi Kimura,2 Hideki Komatsu,2 Masatomo Ishikawa,2 Tadashi Hasegawa,2 Akihiro Shiina,1 Tasuku Hashimoto,2 Nobuhisa Kanahara,3 Tetsuya Shiraishi,2 Masaomi Iyo1–31Department of Child Psychiatry, Chiba University Hospital, 2Department of Psychiatry, Chiba University Graduate School of Medicine, 3Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, JapanBackground: Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD.Subjects and methods: This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0 received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS, Japanese version, and the Das–Naglieri Cognitive Assessment System (DN-CAS, Japanese version.Results: A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores

Comparison of the effect of a single dose of omeprazole or lansoprazole on intragastric pH in Japanese participants: a two-way crossover study.

Science.gov (United States)

Funaki, Yasushi; Tokudome, Kentaro; Izawa, Shinya; Tamura, Yasuhiro; Kondo, Yoshihiro; Iida, Akihito; Mizuno, Mari; Ogasawara, Naotaka; Sasaki, Makoto; Kasugai, Kunio

2013-03-01

It is known that the pharmacokinetic profile of proton pump inhibitors (PPIs) after postprandial administration may differ among PPIs. The purpose of this study was to compare the inhibitory effects of gastric acid secretion by PPIs administered after a meal, based on a 24-hour intragastric pH monitoring. Ten healthy men who provided written informed consent participated in the study. They were given a 20-mg omeprazole tablet and a 30-mg lansoprazole orally dispersing tablet in a two-way crossover manner. At baseline, the anti-HP-IgG antibody levels in blood and the pepsinogen (PG) I/II ratio were measured. Participants were given a standardized meal and 200 mL of water at 9:30 am, 13:30 pm, and 18.30 pm. Participants took the PPI after breakfast. Two of the ten participants tested positive for Helicobacter pylori infection. The PG I/II ratio indicated negative gastric atrophy in all the participants. The percentage 24-hour intragastric pH > 4 holding times (median, range) with omeprazole and lansoprazole were 29.3, 19.3-50.0% and 27.8, 13.0-42.3%, respectively, which shows that with the administration of omeprazole, the pH was maintained at >4 for a longer period (p lansoprazole (p lansoprazole, a single postprandial dose of omeprazole showed a more rapid and sustained acid-inhibitory effect. Copyright © 2012. Published by Elsevier B.V.

Synthesis of 14C-labeled and stable isotope-labeled CGS 16617

International Nuclear Information System (INIS)

Chaudhuri, N.K.; Markus, B.; Sung Mingsang

1988-01-01

The synthesis of a 14 C-labeled and two stable isotope-labeled analogs of CGS 16617 is described. The synthetic method involved the preparation of tetrahydro-3-bromo-1-benzazepin-2-one, labeled with a 14 C or four deuterium atoms, followed by introduction of two side chains at 1- and 3-positions. The labeled bromobenzazepinones were prepared by Beckmann rearrangement of bromo-oximes of α-tetralones, obtained by cyclization of labeled benzenebutanoic acids. The 14 C-labeled acid was prepared by hydrolysis of the nitrile, prepared by reaction of 3-bromopropylbenzene and K 14 CN. The tetradeutero acid was prepared from ethyl phenylpropynoate by catalytic reduction of the triple bond with deuterium gas, followed by reduction of the deuterated ester with lithium aluminium hydride and conversion of the resulting alcohol into the carboxylic acid. The acetic acid side chain was introduced by N-alkylation with ethyl bromoacetate or ethyl bromoacetate-1, 2- 13 C 2 followed by hydrolysis, and the L-lysine side chain, by reaction with L-(-)-3-amino-ε-caprolactam followed by hydrolysis of the caprolactam ring. (author)

A comparative pharmacokinetic study of a fixed dose combination for essential hypertensive patients: a randomized crossover study in healthy human volunteers.

Science.gov (United States)

Gorain, B; Choudhury, H; Halder, D; Sarkar, A K; Sarkar, P; Biswas, E; Ghosh, B; Pal, T K

2013-04-01

This study was aimed to investigate the relative bioavailability of fixed-dose-combination (FDC) product of amlodipine, telmisartan and hydrochlorothiazide with individual marketed products in healthy male volunteers. Control of blood pressure with fixed dose combination of the above drugs acting through different mechanism have a benefit of convenient dosing in terms of compliance, lower the dose and subsequently reduce the side effects. The authors investigated the relative bioavailability under a fasting state of the 3 drugs in a randomized, open-label, 2-treatment, 2-period, 2-sequence, crossover bioequivalence study with a washout period of 21 days. Plasma concentration of the analytes were assayed in timed samples with a simple, highly sensitive and rapid validated method using HPLC coupled to tandem mass spectrometry that had a lower limit of quantification of 1 ng/mL for all the 3 components. Test and reference formulations gave a mean Cmax of 5.234±0.914 ng/mL and 4.991±0.563 ng/mL, 108.839±13.601 ng/mL and 114.783±12.315 ng/mL and 97.814±10.779 ng/mL and 93.731±10.018 ng/mL for amlodipine, telmisartan and hydrochlorothiazide respectively. The AUC0-t of amlodipine, telmisartan and hydrochlorothiazide was 161.484 ng.h/mL, 1 917.644 ng.h/mL and 822.847 ng.h/mL for test formulation and 162.108 ng.h/mL, 2 014.764 ng.h/mL and 829.323 ng.h/mL for reference in the fasting state. The 90% confidence intervals for the test/reference ratio of the pharmacokinetic parameters in fasting state (mean Cmax, AUC0-t, and AUC0-∞) were within the acceptable range of 80.00-125.00. Thus, these findings clearly indicate that the FDC product is bioequivalent with the individual marketed products in terms of rate and extent of drug absorption and is well tolerated with no significant adverse reactions. © Georg Thieme Verlag KG Stuttgart · New York.

A Rotational Pressure-Correction Scheme for Incompressible Two-Phase Flows with Open Boundaries

Science.gov (United States)

Dong, S.; Wang, X.

2016-01-01

Two-phase outflows refer to situations where the interface formed between two immiscible incompressible fluids passes through open portions of the domain boundary. We present several new forms of open boundary conditions for two-phase outflow simulations within the phase field framework, as well as a rotational pressure correction based algorithm for numerically treating these open boundary conditions. Our algorithm gives rise to linear algebraic systems for the velocity and the pressure that involve only constant and time-independent coefficient matrices after discretization, despite the variable density and variable viscosity of the two-phase mixture. By comparing simulation results with theory and the experimental data, we show that the method produces physically accurate results. We also present numerical experiments to demonstrate the long-term stability of the method in situations where large density contrast, large viscosity contrast, and backflows occur at the two-phase open boundaries. PMID:27163909

Factors affecting the labeling efficiency and stability of technetium-99m-labeled glucoheptonate

International Nuclear Information System (INIS)

Zbrzeznj, D.J.; Khan, R.A.

1981-01-01

Factors influencing the labeling efficiency and in vitro stability of 99 mTc-labeled glucoheptonate (Tc-GH) were investigated. Using commercially available glucoheptonate kits (New England Nuclear), the following factors were studied: (1) amount of activity added to each kit vial, (2) different brands of 0.9% sodium chloride injection, (3) evaluation of eluates from three commercially available generators, (4) different chromatography systems, (5) storage of the preparation at room temperature and under refrigeration, and (6) labeling with eluates obtained at various times (6, 24, 48, 72, and 96 hours) since previous elution of the generator. Results showed that Tc-GH prepared using 100 mCi of sodium pertechnetate from a Mallinckrodt generator, low-dissolved-oxygen 0.9% sodium chloride injection to make up a constant 5-ml volume, and chromatography with methyl ethyl ketone/sodium chloride on an ITLC-SG system gave the best labeling efficiency over a 24-hour period. Storage temperature and time since previous elution had no effect on labeling efficiency or stability

76 FR 30051 - Food Labeling; Nutrition Labeling of Standard Menu Items in Restaurants and Similar Retail Food...

Science.gov (United States)

2011-05-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 11 and 101 [Docket No. FDA-2011-F-0172] RIN 0910-AG57 Food Labeling; Nutrition Labeling of Standard Menu Items in Restaurants and Similar Retail Food Establishments; Extension of Comment Period AGENCY: Food and Drug...

Technetium-99m labelled hydrazinonicotinamido human non-specific polyclonal immunoglobulin G for detection of infectious foci: a comparison with two other technetium-labelled immunoglobulin preparations

Energy Technology Data Exchange (ETDEWEB)

Claessens, R.A.M.J. [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Boerman, O.C. [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Koenders, E.B. [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Oyen, W.J.G. [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Meer, J.W.M. van der [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Corstens, F.H.M. [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands)

1996-04-01

In this study we compared the tissue distribution of three different {sup 99m}Tc-hIgG preparations in groups of five Wistar rats with a focal intramuscular infection with Staphylococcus aureus. We compared {sup 99m}Tc-HYNIC-hIgG with {sup 99m}Tc-hIgG labelled via the so-called Schwarz method (reduction of disulphide bonds) and with the {sup 99m}Tc-labelled commercially available Technescan-HIG. Unlike the HYNIC linker, in the two other labelling methods free sulph-hydryl groups are involved in the binding of {sup 99m}Tc. High-performance liquid chromatography analysis of the labelled preparations and of plasma samples revealed aggregate or polymer formation in all three agents; this was least pronounced in the product labelled by means of the Schwarz method. The tested preparations did not show signs of degradation in vitro. The difference in linker chemistry was reflected in the tissue distribution. Thus the biodistribution of {sup 99m}Tc-HYNIC-hIgG was significantly different from the distribution of the two other preparations: abscess (1.4%{+-}0.2%ID/g), muscle, liver, spleen, plasma, lung, bone marrow, and small intestine concentrations were higher at 24 h p.i.; kidney uptake (1.19%{+-}0.08%ID/g) was significantly lower. The abscess-to-plasma and the abscess-to-muscle ratios (0.5 and 11, respectively), however, were in the same range for the three preparations tested. Quantitative analysis of the scintigraphs revealed that the total body clearance of {sup 99m}Tc-HYNIC-hIgG was significantly slower than for the other agents. The abscess uptake of {sup 99m}Tc-HYNIC-hIgG as a percentage of the remaining body activity was significantly higher. Based on its high abscess uptake, its low uptake in the kidneys and the high percentage of its abscess uptake in relation to the remaining body activity, we conclude that {sup 99m}Tc-HYNIC-hIgG seems superior to the two other preparations tested for the detection of infections. (orig.). With 7 figs., 2 tabs.

The relationship among expressions, labels, and descriptions of contempt.

Science.gov (United States)

Matsumoto, David; Ekman, Paul

2004-10-01

This article reports 4 studies that demonstrate that the contempt expression is reliably associated with situations that elicit contempt and that the inability to label the contempt expression reflects a problem with its label or concept and not with the relationship between its expression and emotion. In Study I, the labeling of contempt in fixed-choice judgment tasks did not occur because of a process of elimination. In Studies 2 and 3, the contempt expression was associated with situations that elicit contempt, but participants did not label the situations in an open-ended response. In Study 3, participants also more reliably labeled the contempt expression with situations rather than with labels and did not generate contempt situations from labels. In Study 4, participants reported using, hearing, and reading about contempt the least among 7 emotions tested. (c) 2004 APA, all rights reserved

A Link between Meiotic Prophase Progression and CrossoverControl

Energy Technology Data Exchange (ETDEWEB)

Carlton, Peter M.; Farruggio, Alfonso P.; Dernburg, Abby F.

2005-07-06

During meiosis, most organisms ensure that homologous chromosomes undergo at least one exchange of DNA, or crossover, to link chromosomes together and accomplish proper segregation. How each chromosome receives a minimum of one crossover is unknown. During early meiosis in Caenorhabditis elegans and many other species, chromosomes adopt a polarized organization within the nucleus, which normally disappears upon completion of homolog synapsis. Mutations that impair synapsis even between a single pair of chromosomes in C. elegans delay this nuclear reorganization. We quantified this delay by developing a classification scheme for discrete stages of meiosis. Immunofluorescence localization of RAD-51 protein revealed that delayed meiotic cells also contained persistent recombination intermediates. Through genetic analysis, we found that this cytological delay in meiotic progression requires double-strand breaks and the function of the crossover-promoting heteroduplex HIM-14 (Msh4) and MSH-5. Failure of X chromosome synapsis also resulted in impaired crossover control on autosomes, which may result from greater numbers and persistence of recombination intermediates in the delayed nuclei. We conclude that maturation of recombination events on chromosomes promotes meiotic progression, and is coupled to the regulation of crossover number and placement. Our results have broad implications for the interpretation of meiotic mutants, as we have shown that asynapsis of a single chromosome pair can exert global effects on meiotic progression and recombination frequency.

Generalized periodic EEG activity in two cases of neurosyphilis

Directory of Open Access Journals (Sweden)

Anghinah Renato

2006-01-01

Full Text Available Neurosyphilis is a recognized cause of epileptic seizures and cognitive impairment, but is not usually associated with the finding of generalized periodic activity in the EEG. We report two similar cases characterized by progressive cognitive impairment followed by partial complex seizures, in whom the EEG showed generalized periodic activity. Both cerebrospinal fluid and the response to penicillin therapy confirmed the diagnoses of neurosyphilis in the two cases. The finding of EEG generalized periodic activity in patients with cognitive or behavioral disorders is usually associated with Creutzfeldt-Jakob disease, although there are other conditions, some of them potentially reversible, which may also present this EEG abnormality. Neurosyphilis has tended not to be included among them, and our present findings support the importance of first ruling out neurosyphilis in those patients with cognitive or behavioral disorders associated with generalized periodic epileptiform discharges.

99Tcsup(m)-HMPAO labelled leucocytes: comparison with 111In-tropolonate labelled granulocytes

International Nuclear Information System (INIS)

Peters, A.M.; Roddie, M.E.; Zacharopoulos, G.P.; George, P.; Stuttle, A.W.J.; Lavender, J.P.; Danpure, H.J.; Osman, S.

1988-01-01

The lipophilic complex, 99 Tcsup(m)-hexamethylpropyleneamine oxime (HMPAO) is an efficient leucocyte label, and labels granulocytes with more stability than mononuclear leucocytes. The recovery of 99 Tcsup(m)-HMPAO granulocytes was similar to 111 In-labelled granulocytes isolated and labelled in plasma using tropolone. The Tsub(1/2) of 99 Tcsup(m)-HMPAO labelled granulocytes in blood was less than that of 111 In-labelled granulocytes. The initial biodistribution of 99 Tcsup(m)-labelled leucocytes was similar to 111 In-labelled granulocytes, with a rapid initial lung transit, prominent splenic activity, bone marrow activity and minimal hepatic activity, although, unlike 111 In, 99 Tcsup(m) activity was also seen in urine, occasionally in the gallbladder, and, from about 4 h, consistently in the colon. Bone marrow activity was particularly prominent with 99 Tcsup(m). About 6% of 99 Tcsup(m) was excreted in the faeces up to 48 h after injection, and about 17% in urine up to 24 h. The time-activity curves of reticuloendothelial activity up to 24 h were broadly similar for the two labelled cell preparations. Clinical information given by the two agents was similar in 27 of 30 patients who received both. We conclude that with respect to granulocyte kinetics and clinical data, 99 Tcsup(m)-HMPAO labelled leucocytes are comparable with 111 In-tropolonate labelled granulocytes. (author)

Two Open-Ended, Experiential Learning Cases in Accounting

Science.gov (United States)

Fuglister, Jayne; Stegmoyer, Matthew; Castrigano, Renee

2010-01-01

The rapidly changing environment in international business provides an excellent opportunity for instructors to design timely, adaptable, experiential learning, and open-ended cases. This paper presents and discusses how to prepare and use two such cases in the areas of bank accounting and international accounting. The cases can be offered and…

Diets with high-fat cheese, high-fat meat, or carbohydrate on cardiovascular risk markers in overweight postmenopausal women

DEFF Research Database (Denmark)

Thorning, Tanja Kongerslev; Raziani, Farinaz; Bendsen, Nathalie Tommerup

2015-01-01

BACKGROUND: Heart associations recommend limited intake of saturated fat. However, effects of saturated fat on low-density lipoprotein (LDL)-cholesterol concentrations and cardiovascular disease risk might depend on nutrients and specific saturated fatty acids (SFAs) in food. OBJECTIVE: We explored...... the effects of cheese and meat as sources of SFAs or isocaloric replacement with carbohydrates on blood lipids, lipoproteins, and fecal excretion of fat and bile acids. DESIGN: The study was a randomized, crossover, open-label intervention in 14 overweight postmenopausal women. Three full-diet periods of 2-wk...... duration were provided separated by 2-wk washout periods. The isocaloric diets were as follows: 1) a high-cheese (96-120-g) intervention [i.e., intervention containing cheese (CHEESE)], 2) a macronutrient-matched nondairy, high-meat control [i.e., nondairy control with a high content of high-fat processed...

Gatifloxacin versus chloramphenicol for uncomplicated enteric fever: an open-label, randomised, controlled trial.

Science.gov (United States)

Arjyal, Amit; Basnyat, Buddha; Koirala, Samir; Karkey, Abhilasha; Dongol, Sabina; Agrawaal, Krishna Kumar; Shakya, Nikki; Shrestha, Kabina; Sharma, Manish; Lama, Sanju; Shrestha, Kasturi; Khatri, Nely Shrestha; Shrestha, Umesh; Campbell, James I; Baker, Stephen; Farrar, Jeremy; Wolbers, Marcel; Dolecek, Christiane

2011-06-01

We aimed to investigate whether gatifloxacin, a new generation and affordable fluoroquinolone, is better than chloramphenicol for the treatment of uncomplicated enteric fever in children and adults. We did an open-label randomised superiority trial at Patan Hospital, Kathmandu, Nepal, to investigate whether gatifloxacin is more effective than chloramphenicol for treating uncomplicated enteric fever. Children and adults clinically diagnosed with enteric fever received either gatifloxacin (10 mg/kg) once a day for 7 days, or chloramphenicol (75 mg/kg per day) in four divided doses for 14 days. Patients were randomly allocated treatment (1:1) in blocks of 50, without stratification. Allocations were placed in sealed envelopes opened by the study physician once a patient was enrolled into the trial. Masking was not possible because of the different formulations and ways of giving the two drugs. The primary outcome measure was treatment failure, which consisted of at least one of the following: persistent fever at day 10, need for rescue treatment, microbiological failure, relapse until day 31, and enteric-fever-related complications. The primary outcome was assessed in all patients randomly allocated treatment and reported separately for culture-positive patients and for all patients. Secondary outcome measures were fever clearance time, late relapse, and faecal carriage. The trial is registered on controlled-trials.com, number ISRCTN 53258327. 844 patients with a median age of 16 (IQR 9-22) years were enrolled in the trial and randomly allocated a treatment. 352 patients had blood-culture-confirmed enteric fever: 175 were treated with chloramphenicol and 177 with gatifloxacin. 14 patients had treatment failure in the chloramphenicol group, compared with 12 in the gatifloxacin group (hazard ratio [HR] of time to failure 0·86, 95% CI 0·40-1·86, p=0·70). The median time to fever clearance was 3·95 days (95% CI 3·68-4·68) in the chloramphenicol group and 3·90 days

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

Science.gov (United States)

Carhart-Harris, Robin L; Bolstridge, Mark; Rucker, James; Day, Camilla M J; Erritzoe, David; Kaelen, Mendel; Bloomfield, Michael; Rickard, James A; Forbes, Ben; Feilding, Amanda; Taylor, David; Pilling, Steve; Curran, Valerie H; Nutt, David J

2016-07-01

Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1

The efficacy of cetirizine hydrochloride on the pruritus of cats with atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover study.

Science.gov (United States)

Wildermuth, Kerstin; Zabel, Sonja; Rosychuk, Rod A W

2013-12-01

Various antihistamines have been used in the management of feline atopic dermatitis, with variable reported benefit. To date, there have been no randomized, double-blind, placebo-controlled, crossover clinical trials on the use of this drug class in cats. To evaluate the clinical efficacy of cetirizine hydrochloride for the control of pruritus and dermatitis in cats diagnosed with atopic dermatitis. In this randomized, double-blind, placebo-controlled crossover clinical trial, 21 client-owned cats diagnosed with mild to moderate nonseasonal atopic dermatitis were randomly assigned to two groups. Cats in each group received either 1 mg/kg cetirizine hydrochloride or placebo once daily per os for 28 days followed by a 14 day wash-out period. Treatments were then crossed over, and cats received placebo or cetirizine hydrochloride for another 28 days. Owners marked a pruritus severity scale before inclusion in the study and weekly throughout the entire study period. Lesions were scored by the clinician using a Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03 modified for the cat before enrolment and at day 28 of each treatment. Nineteen cats completed the study. There were no statistically significant differences between treatment with cetirizine hydrochloride and placebo for modified CADESI-03 or pruritus scores. This study suggests that cetirizine hydrochloride cannot be recommended for the management of feline atopic dermatitis. © 2013 ESVD and ACVD.

Ease of use and patient preference injection simulation study comparing two prefilled insulin pens.

Science.gov (United States)

Clark, Paula E; Valentine, Virginia; Bodie, Jennifer N; Sarwat, Samiha

2010-07-01

To determine patient ease of use and preference for the Humalog KwikPen* (prefilled insulin lispro [Humalog dagger] pen, Eli Lilly and Company, Indianapolis, IN, USA) (insulin lispro pen) versus the Next Generation FlexPen double dagger (prefilled insulin aspart [NovoRapid section sign ] pen, Novo Nordisk A/S, Bagsvaerd, Denmark) (insulin aspart pen). This was a randomized, open-label, 2-period, 8-sequence crossover study in insulin pen-naïve patients with diabetes. Randomized patients (N = 367) received device training, then simulated low- (15 U) and high- (60 U) dose insulin injections with an appliance. Patients rated pens using an ease of use questionnaire and were asked separately for final pen preferences. The Insulin Device 'Ease of Use' Battery is a 10-item questionnaire with a 7-point scale (higher scores reflect greater ease of use). The primary objective was to determine pen preference for 'easy to press to inject my dose' (by comparing composite scores [low- plus high-dose]). Secondary objectives were to determine pen preference on select questionnaire items (from composite scores), final pen preference, and summary responses for all questionnaire items. On the primary endpoint, 'easy to press to inject my dose,' a statistically significant majority of patients with a preference chose the insulin lispro pen over the insulin aspart pen (68.4%, 95% CI = 62.7-73.6%). Statistically significant majorities of patients with a preference also favored the insulin lispro pen on secondary items: 'easy to hold in my hand when I inject' (64.9%, 95% CI = 58.8-70.7%), 'easy to use when I am in a public place' (67.5%, 95% CI = 61.0-73.6%), and 'overall easy to use' (69.9%, 95% CI = 63.9-75.4%). A statistically significant majority of patients had a final preference for the insulin lispro pen (67.3%, 95% CI = 62.2-72.1%). Among pen-naïve patients with diabetes who had a preference, the majority preferred the insulin lispro pen over the insulin aspart pen with regard

Test Equality between Three Treatments under an Incomplete Block Crossover Design.

Science.gov (United States)

Lui, Kung-Jong

2015-01-01

Under a random effects linear additive risk model, we compare two experimental treatments with a placebo in continuous data under an incomplete block crossover trial. We develop three test procedures for simultaneously testing equality between two experimental treatments and a placebo, as well as interval estimators for the mean difference between treatments. We apply Monte Carlo simulations to evaluate the performance of these test procedures and interval estimators in a variety of situations. We note that the bivariate test procedure accounting for the dependence structure based on the F-test is preferable to the other two procedures when there is only one of the two experimental treatments has a non-zero effect vs. the placebo. We note further that when the effects of the two experimental treatments vs. a placebo are in the same relative directions and are approximately of equal magnitude, the summary test procedure based on a simple average of two weighted-least-squares (WLS) estimators can outperform the other two procedures with respect to power. When one of the two experimental treatments has a relatively large effect vs. the placebo, the univariate test procedure with using Bonferroni's equality can be still of use. Finally, we use the data about the forced expiratory volume in 1 s (FEV1) readings taken from a double-blind crossover trial comparing two different doses of formoterol with a placebo to illustrate the use of test procedures and interval estimators proposed here.

The insulin-like growth factor axis and collagen turnover in asthmatic children treated with inhaled budesonide

DEFF Research Database (Denmark)

Wolthers, O D; Juul, A; Hansen, M

1995-01-01

) and the amino terminal propeptide of type III procollagen (PIIINP) were studied in 14 prepubertal children with asthma (mean age 9.7 years) during treatment with inhaled budesonide. The study design was a randomized, crossover trial with two double-blind treatment periods (200 and 800 micrograms) and one open......, non-randomized treatment period (400 micrograms). All periods were 18 days' duration. Budesonide treatment was associated with a dose-related suppressive trend in serum concentrations of PIIINP when the 400 micrograms period was included (p

Two-period resource duopoly with endogenous intertemporal capacity constraints

International Nuclear Information System (INIS)

Berk, Istemi

2014-01-01

This paper analyzes the strategic firm behavior within the context of a two-period resource duopoly model in which firms face endogenous intertemporal capacity constraints. Firms are allowed to invest in capacity in between two periods in order to increase their initial endowment of exhaustible resource stocks. Using this setup, we nd that the equilibrium price weakly decreases over time. Moreover, asymmetric distribution of initial resource stocks leads to a significant change in equilibrium outcome, provided that firms do not have the same cost structure in capacity additions. It is also verified that if only one company is capable of investment in capacity, the market moves to a more concentrated structure in the second period.

Two-period resource duopoly with endogenous intertemporal capacity constraints

Energy Technology Data Exchange (ETDEWEB)

Berk, Istemi

2014-07-15

This paper analyzes the strategic firm behavior within the context of a two-period resource duopoly model in which firms face endogenous intertemporal capacity constraints. Firms are allowed to invest in capacity in between two periods in order to increase their initial endowment of exhaustible resource stocks. Using this setup, we nd that the equilibrium price weakly decreases over time. Moreover, asymmetric distribution of initial resource stocks leads to a significant change in equilibrium outcome, provided that firms do not have the same cost structure in capacity additions. It is also verified that if only one company is capable of investment in capacity, the market moves to a more concentrated structure in the second period.

The spatial regulation of meiotic recombination hotspots: are all DSB hotspots crossover hotspots?

Science.gov (United States)

Serrentino, Maria-Elisabetta; Borde, Valérie

2012-07-15

A key step for the success of meiosis is programmed homologous recombination, during which crossovers, or exchange of chromosome arms, take place. Crossovers increase genetic diversity but their main function is to ensure accurate chromosome segregation. Defects in crossover number and position produce aneuploidies that represent the main cause of miscarriages and chromosomal abnormalities such as Down's syndrome. Recombination is initiated by the formation of programmed double strand breaks (DSBs), which occur preferentially at places called DSB hotspots. Among all DSBs generated, only a small fraction is repaired by crossover, the other being repaired by other homologous recombination pathways. Crossover maps have been generated in a number of organisms, defining crossover hotspots. With the availability of genome-wide maps of DSBs as well as the ability to measure genetically the repair outcome at several hotspots, it is becoming more and more clear that not all DSB hotspots behave the same for crossover formation, suggesting that chromosomal features distinguish different types of hotspots. Copyright © 2012. Published by Elsevier Inc.

Microbial status and product labelling of 58 original tattoo inks.

Science.gov (United States)

Høgsberg, T; Saunte, D M; Frimodt-Møller, N; Serup, J

2013-01-01

European Council resolutions on tattoo ink introduce sterility and preservation of inks to protect customers. Inks used in Denmark are typically purchased over the internet from international suppliers and manufacturers from the US and the UK. In Denmark tattoo inks are regulated and labelled according to REACH as if they were plain chemicals. The objective of this study was to check the microbial product safety of unopened and opened tattoo ink stock bottles. Packaging, labelling, preservation, sterility and contamination with micro-organisms were studied. Physical inspection and culture of bacteria and fungi. Six of 58 unopened stock bottles (10%) were contaminated with bacteria and one of six samples (17%) of previously used stock bottles was contaminated. The bacterial species represented bacteria considered pathogenic in humans as well as non-pathogenic environmental bacteria. Yeast or moulds were detected in none of the samples. A total of 31% of the manufacturers informed only about the brand name. No information about content, sterility, risks or expiry date was indicated on the label. A total of 42% claimed sterility of their inks. A total of 54% labelled a maximum period of durability of typically 2-3 years. The physical sealing was leaking in 28% of the products. The European Council resolutions regarding safety of tattoo inks are not effective. Stock bottles of tattoo ink may contain bacteria pathogenic to humans and environmental bacteria, and packaging, labelling and preservation of inks are of inadequate quality. Claim of sterility can be erroneous. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Studies on processes of damage and the stability of two preparations of human growth hormone labelled with 125I

International Nuclear Information System (INIS)

Fonseca, M.L.C.Q.

1978-01-01

Two HGH preparations were studied to obtain stable 125 I labelled products, with high specific activity, good biding capacity and long shelf life. Alterations affecting unlabelled protein hormone were also considered. Modified polyacrylamide gel electrophoresis and gel filtration chromatography on Sephadex were studied. The preparations studied were: HGH (NIH) and HGH always freshly prepared at IEA. The detection, study on nature and elimination of the interference of 'damaged' radioactive components was done by checking their presence and behaviour during labelling, purification or storage and comparing with some 'false labelling' (without HGH). Both hormones were labelled with a high specific activity, with immunoactivity up to three months. Loss in binding happened during storage for radioactive products as well as for unlabelled proteins. The absence of Bovine Serum Albumine (BSA) used as protein carrier and protector, produced a peak of aggregate; when presented, BSA carried a large amount of radioactivity forming most of the 'peak of the damage product' eluting from Sephadex. These two peaks interfere negatively in RIA and can effect calculations on specific activity, yield and absolute amount in term of mass of the labelled product. The best conditions for storage are at-20 0 C in dry lyophilized powder or frozen solution; at 4 0 C in solution the product is inactivated. Both labelled products showed an increased mobility in comparison with the unlabelled done. This can be attributed to a decreased isoelectric point due to the iodination of tyrosine or to alterations in the structure caused by reagents used in the labelling [pt

Comparison of efficacy of transversus abdominis plane block and iliohypogastric/ilioinguinal nerve block for postoperative pain management in patients undergoing inguinal herniorrhaphy with spinal anesthesia: a prospective randomized controlled open-label study.

Science.gov (United States)

Okur, Onur; Tekgul, Zeki Tuncel; Erkan, Nazif

2017-10-01

The purpose of this study was to compare the effects of lateral abdominal transversus abdominis plane block (TAP block) and iliohypogastric/ilioinguinal nerve block (IHINB) under ultrasound guidance for postoperative pain management of inguinal hernia repair. Secondary purposes were to compare the complication rates of the two techniques and to examine the effects of TAP block and IHINB on chronic postoperative pain. This was a prospective randomized controlled open-label study. After approval of the Research Ethics Board, a total of 90 patients were allocated to three groups of 30 by simple randomized sampling as determined with a priori power analysis. Peripheral nerve blocks (TAP block or IHINB) were administered to patients following subarachnoid block according to their allocated group. Patient pain scores, additional analgesic requirements and complication rates were recorded periodically and compared. Pain scores were significantly lower in the study groups (p block group [GT] 266.6 ± 119.7 min; IHINB group [GI] 247.2 ± 128.7 min; and control group [GC] 79.1 ± 66.2 min; p block or IHINB for patients undergoing inguinal herniorrhaphy reduces the intensity of both acute and chronic postoperative pain and additional analgesic requirements.

The optimal injection technique for the osteoarthritic ankle: A randomized, cross-over trial

NARCIS (Netherlands)

Witteveen, Angelique G. H.; Kok, Aimee; Sierevelt, Inger N.; Kerkhoffs, Gino M. M. J.; van Dijk, C. Niek

2013-01-01

Background: To optimize the injection technique for the osteoarthritic ankle in order to enhance the effect of intra-articular injections and minimize adverse events. Methods: Randomized cross-over trial. Comparing two injection techniques in patients with symptomatic ankle osteoarthritis. Patients

N-Acetylcysteine for Nonsuicidal Self-Injurious Behavior in Adolescents: An Open-Label Pilot Study.

Science.gov (United States)

Cullen, Kathryn R; Klimes-Dougan, Bonnie; Westlund Schreiner, Melinda; Carstedt, Patricia; Marka, Nicholas; Nelson, Katharine; Miller, Michael J; Reigstad, Kristina; Westervelt, Ana; Gunlicks-Stoessel, Meredith; Eberly, Lynn E

2018-03-01

Nonsuicidal self-injury (NSSI) is common in adolescents and young adults, and few evidence-based treatments are available for this significant problem. N-acetylcysteine (NAC) is a widely available nutritional supplement that has been studied in some psychiatric disorders relevant to NSSI including mood and addictive disorders. This pilot study tested the use of NAC as a potential treatment for NSSI in youth. Thirty-five female adolescents and young adults with NSSI aged 13-21 years were enrolled in this study that had an open-label, single-arm study design. All participants were given oral NAC as follows: 600 mg twice daily (weeks 1-2), 1200 mg twice daily (weeks 3-4), and 1800 mg twice daily (weeks 5-8). Patients were seen every 2 weeks throughout the trial, at which time youth reported the frequency of NSSI episodes. Levels of depression, impulsivity, and global psychopathology were measured at baseline and at the end of the trial using the Beck Depression Inventory-II (BDI-II), Barratt Impulsivity Scale, and Symptoms Checklist-90 (SCL-90). About two-thirds of the enrolled female youth completed the trial (24/35). NAC was generally well tolerated in this sample. NAC treatment was associated with a significant decrease in NSSI frequency at visit 6 and visit 8 compared to baseline. We also found that depression scores and global psychopathology scores (but not impulsivity scores) decreased after NAC treatment. Decrease in NSSI was not correlated with decrease in BDI-II or SCL-90 scores, suggesting these might be independent effects. We provide preliminary evidence that NAC may have promise as a potential treatment option for adolescents with NSSI. The current results require follow-up with a randomized, placebo-controlled trial to confirm efficacy.

The German East-West Mortality Difference: Two Crossovers Driven by Smoking.

Science.gov (United States)

Vogt, Tobias; van Raalte, Alyson; Grigoriev, Pavel; Myrskylä, Mikko

2017-06-01

Before the fall of the Berlin Wall, mortality was considerably higher in the former East Germany than in West Germany. The gap narrowed rapidly after German reunification. The convergence was particularly strong for women, to the point that Eastern women aged 50-69 now have lower mortality despite lower incomes and worse overall living conditions. Prior research has shown that lower smoking rates among East German female cohorts born in the 1940s and 1950s were a major contributor to this crossover. However, after 1990, smoking behavior changed dramatically, with higher smoking intensity observed among women in the eastern part of Germany. We forecast the impact of this changing smoking behavior on East-West mortality differences and find that the higher smoking rates among younger East German cohorts will reverse their contemporary mortality advantage. Mortality forecasting methods that do not account for smoking would, perhaps misleadingly, forecast a growing mortality advantage for East German women. Experience from other countries shows that smoking can be effectively reduced by strict anti-smoking policies. Instead, East Germany is becoming an example warning of the consequences of weakening anti-smoking policies and changing behavioral norms.

A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women.

Science.gov (United States)

Brache, Vivian; Merkatz, Ruth; Kumar, Narender; Jesam, Cristian; Sussman, Heather; Hoskin, Elena; Roberts, Kevin; Alami, Mohcine; Taylor, Deshawn; Jorge, Aidelis; Croxatto, Horacio; Lorange, Ellen; Mishell, Daniel R; Sitruk-Ware, Regine

2015-10-01

This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95% of cycles. This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. Eighteen participants were randomized; 16 completed the study. Median NES C(max) values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7%) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods. Copyright © 2015 Elsevier Inc. All rights reserved.

The safety and effectiveness of open-label extended-release carbamazepine in the treatment of children and adolescents with bipolar I disorder suffering from a manic or mixed episode

Directory of Open Access Journals (Sweden)

Findling RL

2014-08-01

Full Text Available Robert L Findling,1,2 Lawrence D Ginsberg31Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, 2Kennedy Krieger Institute, Baltimore, MD, USA; 3Red Oak Psychiatry Associates, PA, Houston, TX, USAObjective: To assess the safety and effectiveness of open-label treatment with extended-release carbamazepine (ERC in pediatric subjects suffering from bipolar I disorder.Method: Medically healthy youths aged 10–17 years suffering from an acute manic or mixed episode were eligible. After screening for study eligibility, the youths began a 5-week titration period in which doses of ERC were adjusted in order to optimize benefit whilst minimizing adverse events, at doses between 200–1,200 mg/day. Thereafter, subjects could continue to receive treatment during a subsequent 21-week period. Safety measures included spontaneously reported adverse events (AEs and laboratory assessments. The primary efficacy measure was the Young Mania Rating Scale (YMRS.Results: A total of 60 children (ages 10–12 and 97 adolescents (ages 13–17, with an overall average age of 13.4 years (standard deviation [SD] 2.0 years received ERC. The mean duration of study participation was 109.6 days (SD 70.2 days, with 66 (42% completing the entire study. At end of study participation (end point, the most prevalent dose of ERC was 1,200 mg: 31.7% of children and 24.7% of adolescents reached the 1,200 mg dose. The YMRS decreased from a mean of 28.6 (SD 6.2 at baseline to a mean of 13.8 (SD 9.4 (P<0.0001 at end point. A total of 26 subjects discontinued study participation because of AEs, the most common of which were rash (n=6, white blood cell count decreased (n=5, nausea (n=3, and vomiting (n=3. No deaths were reported. The most commonly reported AEs were headache (n=41, somnolence (n=30, nausea (n=22, dizziness (n=21, and fatigue (n=19.Conclusions: Open-label administration of ERC might be a safe

Lung transit of /sup 111/Indium-labelled granulocytes. Relationship to labelling techniques

Energy Technology Data Exchange (ETDEWEB)

Saverymuttu, S.H.; Peters, A.M.; Danpure, H.J.; Reavy, H.J.; Osman, S.; Lavender, J.P. (Hammersmith Hospital, London, England)

1983-01-01

The early in vivo distribution of /sup 111/Indium-labelled granulocytes, recorded by dynamic imaging using a gamma camera and computer, varied according to the separation and labelling technique. Following i.v. bolus injection, 4 kinetic patterns could be identified: (A) rapid transit through the pulmonary vasculature, (B) delayed transit through the lung with clearance by about 30 min, (C) complete retention by the lung, for up to 10 min, followed by slow release over a period of 1 to 2 h, (D) delayed transit through the lung with a similar time course to (B) but with subsequent heavy liver uptake. Granulocytes labelled with /sup 111/In-tropolonate and maintained in plasma throughout the labelling procedure, whether injected as a 'pure' (separated by plasma-enriched density gradient centrifugation) or 'crude' (seprated by differential centrifugation) preparation, displayed type A kinetics, thought to most closely represent the normal behaviour of granulocytes. 'Crude' cells labelled in saline with /sup 111/In-acetylacetonate displayed type B kinetics. 'Pure' cells isolated on Percoll-saline and labelled in saline with /sup 111/In-acetylacetonate displayed type C kinetics, thought to represent granulocyte 'stimulation' and/or damage, or type D kientics, thought to represent severe damage. The importance is stressed of labelling granulocytes for kinetic studies with a technique that results in minimal alteration of cell behaviour.

A multicenter study benchmarks software tools for label-free proteome quantification.

Science.gov (United States)

Navarro, Pedro; Kuharev, Jörg; Gillet, Ludovic C; Bernhardt, Oliver M; MacLean, Brendan; Röst, Hannes L; Tate, Stephen A; Tsou, Chih-Chiang; Reiter, Lukas; Distler, Ute; Rosenberger, George; Perez-Riverol, Yasset; Nesvizhskii, Alexey I; Aebersold, Ruedi; Tenzer, Stefan

2016-11-01

Consistent and accurate quantification of proteins by mass spectrometry (MS)-based proteomics depends on the performance of instruments, acquisition methods and data analysis software. In collaboration with the software developers, we evaluated OpenSWATH, SWATH 2.0, Skyline, Spectronaut and DIA-Umpire, five of the most widely used software methods for processing data from sequential window acquisition of all theoretical fragment-ion spectra (SWATH)-MS, which uses data-independent acquisition (DIA) for label-free protein quantification. We analyzed high-complexity test data sets from hybrid proteome samples of defined quantitative composition acquired on two different MS instruments using different SWATH isolation-window setups. For consistent evaluation, we developed LFQbench, an R package, to calculate metrics of precision and accuracy in label-free quantitative MS and report the identification performance, robustness and specificity of each software tool. Our reference data sets enabled developers to improve their software tools. After optimization, all tools provided highly convergent identification and reliable quantification performance, underscoring their robustness for label-free quantitative proteomics.

The effect of reflexotherapy and massage therapy on vital signs and stress before coronary angiography: An open-label clinical trial.

Science.gov (United States)

Khaledifar, Ali; Nasiri, Marzeih; Khaledifar, Borzoo; Khaledifar, Arsalan; Mokhtari, Ali

2017-03-01

Complementary medicine interventions are now successfully used to reduce stress as well as to stabilize hemodynamic indices within different procedures. The present study aimed to examine the effect of massage therapy and reflexotherapy on reducing stress in patients before coronary angiography. In this open-label clinical trial, 75 consecutive patients who were candidate for coronary angiography were randomly assigned to receive reflexotherapy (n = 25), or massage therapy (n = 25), or routine care (n = 25) before angiography. The Spielberger State-Trait Anxiety Inventory was used to determine the stress level of patients before and after interventions and vital signs were also measured. Improvement in diastolic blood pressure, heart rate, and respiratory rate was shown in the reflexotherapy group, and similar effects were observed following other interventions including massage therapy and routine resting program. In subjects who received reflexotherapy the level of stress decreased slightly compared with the other two groups. However, following interventions the level of stress in reflexotherapy group was shown to be lower than other study groups. Reflexotherapy before coronary angiography can help to stabilize vital sign as well as reduce the level of stress. The effect of massage therapy was limited to reducing stress.

Comparison of several hydrological cycle parameters in Croatia for two periods

International Nuclear Information System (INIS)

Pandzic, Kreso; Trninic, Dusan

2004-01-01

Comparison of several hydrological cycle parameter averages for two periods in Croatia is considered. Parameters are: yearly averages of: 2m air temperature, precipitation amounts, potential and real evapotranspiration amounts. A basic period (1951-1980) and period for comparison (1981-1997) have been chosen. (These periods accepted at The First Sub-Regional Expert Meeting on the 'Assesment of Climate Change Impacts on the Hydrological Cycles in South-Eastern Europe' held in Sofia (Bulgaria) 17-20 February 1999.) Differences between two period averages for 30 weather stations have been calculated. Temperature differences and those for potential evaporation are positive while for precipitation they are mainly negative. Real evaporation differences for two periods are an exception i.e. they are positive in continental but negative in Mediterranean part of Croatia. These results agree with global warming trend. (Author)

Vortex profiles and vortex interactions at the electroweak crossover

OpenAIRE

Chernodub, M. N.; Ilgenfritz, E. -M.; Schiller, A.

1999-01-01

Local correlations of Z-vortex operators with gauge and Higgs fields (lattice quantum vortex profiles) as well as vortex two-point functions are studied in the crossover region near a Higgs mass of 100 GeV within the 3D SU(2) Higgs model. The vortex profiles resemble certain features of the classical vortex solutions in the continuum. The vortex-vortex interactions are analogous to the interactions of Abrikosov vortices in a type-I superconductor.

Menu labeling perception and health behaviors among immigrant and US born minority populations: assessment in two Los Angeles public markets.

Science.gov (United States)

Vargas-Bustamante, Arturo

2013-01-01

To analyze menu labeling perception and food choices/health behaviors in two Los Angeles public markets. Labels with food caloric content were displayed in the food court of one of these markets. Bivarate means analyses compared the surveyed population by market and by nativity status. The main predictors of menu-labeling influence were identified in the sample from the market that displayed labels. A separate analysis investigated food choices/health behaviors among immigrant cohorts by time of US residence. Reading labels when shopping was one of the main predictors associated with menu labeling influence. Longer-stayed immigrants were more likely to afford "balanced meals", but they were also more likely to eat in fast food restaurants and less likely to engage into moderate/intense physical activity. While nativity was not a significant predictor of menu labeling influence on food choices, our findings suggest food choices/behaviors convergence among immigrant and US-born populations.

Investigation of iron spin crossover pressure in Fe-bearing MgO using hybrid functional

Science.gov (United States)

Cheng, Ya; Wang, Xianlong; Zhang, Jie; Yang, Kaishuai; Zhang, Chuanguo; Zeng, Zhi; Lin, Haiqin

2018-04-01

Pressure-induced spin crossover behaviors of Fe-bearing MgO were widely investigated by using an LDA  +  U functional for describing the strongly correlated Fe–O bonding. Moreover, the simulated spin crossover pressures depend on the applied U values, which are sensitive to environments and parameters. In this work, the spin crossover pressures of (Mg1‑x ,Fe x )O are investigated by using the hybrid functional with a uniform parameter. Our results indicate that the spin crossover pressures increase with increasing iron concentration. For example, the spin crossover pressure of (Mg0.03125,Fe0.96875)O and FeO was 56 GPa and 127 GPa, respectively. The calculated crossover pressures agreed well with the experimental observations. Therefore, the hybrid functional should be an effective method for describing the pressure-induced spin crossover behaviors in transition metal oxides.

ML-MG: Multi-label Learning with Missing Labels Using a Mixed Graph

KAUST Repository

Wu, Baoyuan

2015-12-07

This work focuses on the problem of multi-label learning with missing labels (MLML), which aims to label each test instance with multiple class labels given training instances that have an incomplete/partial set of these labels (i.e. some of their labels are missing). To handle missing labels, we propose a unified model of label dependencies by constructing a mixed graph, which jointly incorporates (i) instance-level similarity and class co-occurrence as undirected edges and (ii) semantic label hierarchy as directed edges. Unlike most MLML methods, We formulate this learning problem transductively as a convex quadratic matrix optimization problem that encourages training label consistency and encodes both types of label dependencies (i.e. undirected and directed edges) using quadratic terms and hard linear constraints. The alternating direction method of multipliers (ADMM) can be used to exactly and efficiently solve this problem. To evaluate our proposed method, we consider two popular applications (image and video annotation), where the label hierarchy can be derived from Wordnet. Experimental results show that our method achieves a significant improvement over state-of-the-art methods in performance and robustness to missing labels.