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Sample records for once-daily mometasone furoate

  1. Mometasone furoate in the management of asthma: a review

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    Ricardo A Tan

    2008-09-01

    Full Text Available Ricardo A Tan1, Jonathan Corren21California Allergy and Asthma Medical Group, Los Angeles, CA; 2Allergy Research Foundation, Los Angeles, CA, USAAbstract: Inhaled corticosteroids (ICS have proven to be the most effective and essential therapy for the treatment of bronchial asthma. The 2007 National Asthma Education and Prevention Program guidelines recommend ICS as preferred therapy for patients with mild to severe persistent asthma. Mometasone furoate (MF is a relatively new ICS agent with high affinity for the glucocorticoid receptor. It is approved in the US for maintenance treatment of asthma for patients 4 years of age and older. It has been shown to be well tolerated with no significant adverse side effects observed in clinical trials and post-marketing surveillance. The efficacy of mometasone furoate has been established in large, well-designed studies. In patients with persistent asthma previously treated either with short-acting beta-agonists alone or twice-daily maintenance therapy with ICS, once-daily MF has been shown to be superior to placebo in improving lung function, symptom control, and quality of life; and has shown comparable efficacy compared with budesonide, beclomethasone, and fluticasone. Twice-daily dosing with MF has been demonstrated to successfully allow for reduction or elimination of oral corticosteroids in severe asthmatics.Keywords: inhaled steroids, mometasone furoate, once-daily dosing, asthma, stepwise approach

  2. Mometasone furoate nasal spray for the treatment of asthma

    DEFF Research Database (Denmark)

    Meteran, Howraman; Backer, Vibeke

    2016-01-01

    are the key stone in the treatment of both diseases. Mometasone furoate is a potent synthetic steroid with a very high receptor affinity and a low bioavailability and shown to be superior compared to other inhaled corticosteroids. It is not clear whether the use of mometasone furoate nasal spray (MFNS......) is associated with an improvement in asthma control. AREAS COVERED: This current paper reviews the current knowledge on the effect of mometasone furoate nasal spray in the treatment of asthma and includes clinical trials in which both subjective and objective outcomes are assessed. EXPERT OPINION: To date, only...

  3. Forced degradation of mometasone furoate and development of two RP-HPLC methods for its determination with formoterol fumarate or salicylic acid

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    Ramzia I. El-Bagary

    2016-05-01

    Full Text Available Two simple, selective and precise stability-indicating reversed-phase liquid chromatographic methods were developed and validated for the determination of mometasone furoate in two binary mixtures, with formoterol fumarate (Mixture 1 and salicylic acid (Mixture 2. Also, a forced degradation study of mometasone furoate was carried out including acid and alkali hydrolysis, oxidation, thermal and photo-degradation. For mixture 1, the method was based on isocratic elution using a mobile phase consisting of (Acetonitrile: 3 mM Sodium lauryl sulfate (60:40, v/v at a flow rate of 1 ml min−1. Quantitation was achieved applying dual wavelength detection where mometasone furoate and its degradation products were detected at 247 nm and formoterol fumarate and its degradation product were detected at 214 nm at 30 °C. For mixture 2 and for the forced degradation study, separation was based on isocratic elution of mometasone furoate, its degradation products and salicylic acid on a reversed phase C8 column using a mobile phase consisting of acetonitrile:water:methanol:glacial acetic acid (60:30:10:0.1, v/v at a flow rate of 2 mL min−1. Quantitation was achieved with UV detection at 240 nm. In addition, products from alkaline forced degradation of mometasone furoate were verified by LC–MS. Linearity, accuracy and precision were found to be acceptable over the concentration range of 10–800 μg mL−1 and 5–60 μg mL−1 for mometasone furoate and formoterol fumarate, respectively and over the concentration range of 5–320 μg mL−1 and 20–1280 μg mL−1 for mometasone furoate and salicylic acid, respectively. The two proposed methods could be successfully applied for the routine analysis of the studied drugs in their pharmaceutical preparations without any preliminary separation step.

  4. Randomized Trial of Once-Daily Fluticasone Furoate in Children with Inadequately Controlled Asthma

    DEFF Research Database (Denmark)

    Oliver, Amanda J.; Covar, Ronina A.; Goldfrad, Caroline H.

    2016-01-01

    Objective To evaluate the dose-response, efficacy, and safety of fluticasone furoate (FF; 25 µg, 50 µg, and 100 µg), administered once daily in the evening during a 12-week treatment period to children with inadequately controlled asthma. Study design This was a Phase IIb, multicenter, stratified...

  5. Nasal allergies and beyond: a clinical review of the pharmacology, efficacy, and safety of mometasone furoate

    NARCIS (Netherlands)

    van Drunen, C.; Meltzer, E. O.; Bachert, C.; Bousquet, J.; Fokkens, W. J.

    2005-01-01

    Mometasone furoate nasal spray (MFNS; Nasonex, Schering-Plough Corporation, Kenilworth, NJ, USA) is an effective and well-tolerated intranasal corticosteroid approved for the prophylactic treatment of seasonal allergic rhinitis, and the treatment of perennial allergic rhinitis. MFNS is a potent

  6. Validated high-performance thin-layer chromatographic (HPTLC method for simultaneous determination of nadifloxacin, mometasone furoate, and miconazole nitrate cream using fractional factorial design

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    Kalpana G. Patel

    2016-07-01

    Full Text Available A high-performance thin-layer chromatographic method for simultaneous determination of nadifloxacin, mometasone furoate, and miconazole nitrate was developed and validated as per International Conference on Harmonization guidelines. High-performance thin-layer chromatographic separation was performed on aluminum plates precoated with silica gel 60F254 and methanol:ethyl acetate:toluene: acetonitrile:3M ammonium formate in water (1:2.5:6.0:0.3:0.2, % v/v as optimized mobile phase at detection wavelength of 224 nm. The retardation factor (Rf values for nadifloxacin, mometasone furoate, and miconazole nitrate were 0.23, 0.70, and 0.59, respectively. Percent recoveries in terms of accuracy for the marketed formulation were found to be 98.35–99.76%, 99.36–99.65%, and 99.16–100.25% for nadifloxacin, mometasone furoate, and miconazole nitrate, respectively. The pooled percent relative standard deviation for repeatability and intermediate precision studies was found to be < 2% for three target analytes. The effect of four independent variables, methanol content in total mobile phase, wavelength, chamber saturation time, and solvent front, was evaluated by fractional factorial design for robustness testing. Amongst all four factors, volume of methanol in mobile phase appeared to have a possibly significant effect on retention factor of miconazole nitrate compared with the other two drugs nadifloxacin and mometasone furoate, and therefore it was important to be carefully controlled. In summary, a novel, simple, accurate, reproducible, and robust high-performance thin-layer chromatographic method was developed, which would be of use in quality control of these cream formulations.

  7. Mometasone furoate nasal spray relieves the ocular symptoms of seasonal allergic rhinoconjunctivitis.

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    Igarashi, Tsutomu; Nakazato, Yuri; Kunishige, Tomoyuki; Fujita, Miho; Yamada, Yumi; Fujimoto, Chiaki; Okubo, Kimihiro; Takahashi, Hiroshi

    2012-01-01

    Recent studies have examined the effects of intranasal corticosteroids (INSs) in relieving the ocular symptoms of seasonal allergic rhinoconjunctivitis (SAR) and perennial allergic rhinitis. However, because most of these studies were based on subjective assessments by patients, the associated factors and mechanism of action are unknown. A single-center, randomized, double-blind, parallel-group study was carried out in which patients with SAR were randomly assigned to an INS mometasone furoate nasal spray (MFNS) group or to a placebo group and treated once daily for 4 weeks. Substance P concentrations in tears were measured, ocular and nasal symptoms were recorded by patients in an allergy diary, and findings were recorded by an ophthalmologist. There was no significant difference between treatment groups in the mean change from baseline of substance P concentration in tears after 4 weeks of treatment, but the mean change tended to increase in the placebo group and tended to decrease in the MFNS group (P = 0.089). All ocular and nasal symptom scores, except eye tearing, were significantly lower in the MFNS group than in the placebo group. Furthermore, substance P concentrations were strongly correlated with ocular and nasal symptom scores. In patients with SAR, INSs tend to decrease the substance P concentration in tears, which is correlated with the severity of ocular and nasal symptoms.

  8. Comparative potency of formulations of mometasone furoate in terms of inhibition of ′PIRHR′ in the forearm skin of normal human subjects measured with laser doppler velocimetry

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    Kulhalli Prabhakar

    2005-01-01

    Full Text Available BACKGROUND AND AIMS: Topical glucocorticoid formulations are widely used for effective treatment and control of a variety of dermatoses. Mometasone furoate is a newer corticoid that has high potency but low systemic toxicity. Pharmaceutical factors are known to significantly influence potency and systemic absorption of topically applied glucocorticoids. We studied the potency of "Elocon", a topical formulation of mometasone furoate, compared with two other branded formulations of the same corticoid. METHODS: Corticoid potency was measured by employing a pharmacodynamic parameter of an inhibitory effect of the corticoid on post-ischemic-reactive-hyperemic-response (PIRHR in human forearm skin under occlusive dressing. The PIRHR was expressed in terms of % increase in the skin blood flow (SBF as measured with laser doppler velocimetry (LDV. RESULTS : All three active branded formulations of mometasone furoate produced significant inhibition of PIRHR. The AUC(0-2min of PIRHR was ( Mean ± SEM , Control = 213.52 ± 11.80, Placebo = 209.77 ± 19.31, Formulation A = 119.83 ± 13.71, Formulation C = 53.67 ± 4.85 and Formulation D = 111.46 ± 22.87. Formulation "C" exhibited significantly higher topical anti-inflammatory potency than formulations "A" or "D". CONCLUSIONS: Thus, branded formulations of the same glucocorticoid, mometasone furoate significantly differed in their topical anti-inflammatory potency. "Elocon" was significantly more potent than the two other branded formulations studied.

  9. Regional deposition of mometasone furoate nasal spray suspension in humans.

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    Shah, Samir A; Berger, Robert L; McDermott, John; Gupta, Pranav; Monteith, David; Connor, Alyson; Lin, Wu

    2015-01-01

    Nasal deposition studies can demonstrate whether nasal sprays treating allergic rhinitis and polyposis reach the ciliated posterior nasal cavity, where turbinate inflammation and other pathology occurs. However, quantifying nasal deposition is challenging, because in vitro tests do not correlate to human nasal deposition; gamma scintigraphy studies are thus used. For valid data, the radiolabel must distribute, as the drug, into different-sized droplets, remain associated with the drug in the formulation after administration, and not alter its deposition. Some nasal deposition studies have demonstrated this using homogenous solutions. However, most commercial nasal sprays are heterogeneous suspensions. Using mometasone furoate nasal suspension (MFS), we developed a technique to validate radiolabel deposition as a surrogate for nasal cavity drug deposition and characterized regional deposition and nasal clearance in humans. Mometasone furoate (MF) formulation was spiked with diethylene triamine pentacaetic acid. Both unlabeled and radiolabeled formulations (n = 3) were sprayed into a regionally divided nasal cast. Drug deposition was quantified by high pressure liquid chromatography within each region; radiolabel deposition was determined by gamma camera. Healthy subjects (n = 12) were dosed and imaged for six hours. Scintigraphic images were coregistered with magnetic resonance imaging scans to quantify anterior and posterior nasal cavity deposition and mucociliary clearance. The ratio of radiolabel to unlabeled drug was 1.05 in the nasal cast and regionally appeared to match, indicating that in vivo radiolabel deposition could represent drug deposition. In humans, MFS delivered 86% (9.2) of metered dose to the nasal cavity, approximately 60% (9.1) of metered dose to the posterior nasal cavity. After 15 minutes, mucociliary clearance removed 59% of the initial radiolabel in the nasal cavity, consistent with clearance rates from the ciliated posterior surface. MFS

  10. Effect of intranasal mometasone furoate administered in children with coexisting allergic rhinitis and asthma towards asthma attacks and lung function

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    Ellen P. Gandaputra

    2009-12-01

    during the study. There was >50% improvement in allergic rhinitis symptoms after 4 weeks of treatment (P50% after 8 weeks of treatment (P50% of asthma symptoms, however it is not followed with significant improvement in lung function. No side effects are reported during 8 weeks use of intranasal mometasone furoate.

  11. Potent corticosteroid cream (mometasone furoate) significantly reduces acute radiation dermatitis: results from a double-blind, randomized study

    International Nuclear Information System (INIS)

    Bostroem, Aasa; Lindman, Henrik; Swartling, Carl; Berne, Berit; Bergh, Jonas

    2001-01-01

    Purpose: Radiation-induced dermatitis is a very common side effect of radiation therapy, and may necessitate interruption of the therapy. There is a substantial lack of evidence-based treatments for this condition. The aim of this study was to investigate the effect of mometasone furoate cream (MMF) on radiation dermatitis in a prospective, double-blind, randomized study. Material and methods: The study comprised 49 patients with node-negative breast cancer. They were operated on with sector resection and scheduled for postoperative radiotherapy using photons with identical radiation qualities and dosage to the breast parenchyma. The patients were randomized to receive either MMF or emollient cream. The cream was applied on the irradiated skin twice a week from the start of radiotherapy until the 12th fraction (24 Gy) and thereafter once daily until 3 weeks after completion of radiation. Both groups additionally received non-blinded emollient cream daily. The intensity of the acute radiation dermatitis was evaluated on a weekly basis regarding erythema and pigmentation, using a reflectance spectrophotometer together with visual scoring of the skin reactions. Results: MMF in combination with emollient cream treatment significantly decreased acute radiation dermatitis (P=0.0033) compared with emollient cream alone. There was no significant difference in pigmentation between the two groups. Conclusions: Adding MMF, a potent topical corticosteroid, to an emollient cream is statistically significantly more effective than emollient cream alone in reducing acute radiation dermatitis

  12. Spotlight on fluticasone furoate/vilanterol trifenatate for the once-daily treatment of asthma: design, development and place in therapy

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    Albertson TE

    2016-12-01

    Full Text Available Timothy E Albertson,1–3 Samuel W Bullick,1,3 Michael Schivo,1 Mark E Sutter2,3 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Department of Emergency Medicine, School of Medicine, UC Davis, Sacramento, 3Department of Medicine, Veterans Administration Northern California Health Care System, Mather, CA, USA Abstract: The use of inhaled corticosteroids (ICSs plays a key role in the treatment of asthmatic patients, and international guidelines have designated ICSs as an early maintenance therapy in controlling asthma symptoms. When asthmatic patients remain symptomatic on ICSs, one common option is to add a long-acting beta2 agonist (LABA to the maintenance treatment. Fixed combination inhalers that contain both an ICS and a LABA have been popular for both chronic obstructive pulmonary disease (COPD and asthma. Historically, these inhalers have been dosed twice daily. However, currently, there is a once-daily combination therapy with the ICS fluticasone furoate (FF and the LABA vilanterol trifenatate (VI with indications for use in both COPD and asthma. This dry powder inhaler (DPI comes in two doses of FF (100 or 200 µg both combined with VI (25 µg. This article reviews the clinical trial data for FF, VI and FF/VI combination inhalers and documents the efficacy and safety of once-daily inhaled maintenance therapy by DPI in asthmatic patients. Keywords: fluticasone furoate/vilanterol trifenatate, asthma, long-acting beta2 agonist, inhaled corticosteroid, combined inhaler, persistent asthma, dry powder inhaler  

  13. Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma

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    Woodcock Ashley

    2011-12-01

    Full Text Available Abstract Background Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD evening and twice-daily (BD regimens of the novel inhaled corticosteroid fluticasone furoate (FF in asthma patients. Methods Patients with moderate asthma (age ≥ 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1 40-85% predicted; FEV1 reversibility of ≥ 12% and ≥ 200 ml were randomized to FF or fluticasone propionate (FP regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ≥ 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 μg OD, FF or FP 100 μg BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough FEV1; non-inferiority of FF 200 μg OD and FF 100 μg BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs and 24-hour urinary cortisol excretion were assessed. Results The intent-to-treat population comprised 147 (FF and 43 (FP patients. On Day 28, pre-dose FEV1 showed FF 200 μg OD to be non-inferior (pre-defined limit -110 ml to FF 100 μg BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml; all FF and FP regimens were significantly superior to placebo (p ≤ 0.02. AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 μg OD, 0.75; 100 μg BD, 0.84; p ≤ 0.02. Conclusions FF 200 μg OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose. Trial registration Clinicaltrials.gov; NCT00766090.

  14. Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

    International Nuclear Information System (INIS)

    Hindley, Andrew; Zain, Zakiyah; Wood, Lisa; Whitehead, Anne; Sanneh, Alison; Barber, David; Hornsby, Ruth

    2014-01-01

    Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MF than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected

  15. Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

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    Hindley, Andrew, E-mail: andrew.hindley@lthtr.nhs.uk [Rosemere Cancer Centre, Royal Preston Hospital, Preston (United Kingdom); Zain, Zakiyah [College of Arts and Sciences, Universiti Utara Malaysia, Kedah (Malaysia); Wood, Lisa [Department of Social Sciences, Lancaster Medical School, Lancaster (United Kingdom); Whitehead, Anne [Medical and Pharmaceutical Statistics Research Unit, Lancaster University, Lancaster (United Kingdom); Sanneh, Alison; Barber, David; Hornsby, Ruth [Rosemere Cancer Centre, Royal Preston Hospital, Preston (United Kingdom)

    2014-11-15

    Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MF than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected.

  16. Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis.

    Science.gov (United States)

    Bielory, L; Chun, Y; Bielory, B P; Canonica, G W

    2011-05-01

    Intranasal corticosteroids (INSs) are a mainstay of treatment of allergic rhinitis (AR) nasal symptoms. The INS mometasone furoate nasal spray (MFNS) has well-documented efficacy and safety for the treatment and prophylaxis of nasal symptoms of seasonal AR (SAR) and for the treatment of nasal symptoms of perennial AR (PAR). Increasing interest has focused on whether INSs, including MFNS, may have beneficial effects on the ocular symptoms frequently associated with AR. We performed a meta-analysis of 10 randomized, placebo-controlled trials of the efficacy of MFNS 200 mcg daily in relieving ocular allergy symptoms, including itching/burning, redness, and tearing/watering in both SAR and PAR. Four PAR studies and six SAR studies are included in the analysis. A fixed-effect inverse variance model was used to calculate weighted mean differences, 95% confidence intervals (CIs) for each comparison, and a combined overall treatment effect (Z) with P-value. In both analyses of SAR and PAR studies, including 3132 patients, all individual ocular symptoms were reduced in patients treated with MFNS. Overall treatment effect was significant for all three individual ocular symptoms in the SAR studies (Z = 9.18 for tearing, Z = 10.15 for itching, and Z = 8.88 for redness; P INSs, including MFNS, on ocular symptoms associated with SAR and PAR. © 2011 John Wiley & Sons A/S.

  17. Fluticasone furoate: A new intranasal corticosteroid

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    R Kumar

    2012-01-01

    Full Text Available Intranasal corticosteroids are recommended as one of the first-line therapies for the treatment of allergic rhinitis (AR, especially when associated with nasal congestion and recurrent symptoms. Fluticasone furoate is a novel enhanced-affinity glucocorticoid for the treatment of AR approved by the Food and Drug Administration in 2007 and recently introduced in India. Fluticasone furoate nasal spray is indicated for the treatment of the symptoms of seasonal and perennial AR in patients aged two years and older. This review summarizes the clinical data on fluticasone furoate nasal spray and discusses its role in the management of AR. Important attributes of fluticasone furoate include low systemic bioavailability (<0.5%, 24-h symptom relief with once-daily dosing, comprehensive coverage of both nasal and ocular symptoms, safety and tolerability with daily use, and availability in a side-actuated device that makes medication delivery simple and consistent. With these properties, fluticasone furoate nasal spray has the potential to enhance patient satisfaction and compliance, thus making it a good choice amongst available intranasal steroids.

  18. Effects of mometasone, fluticasone, and montelukast on bone mineral density in adults with asthma

    DEFF Research Database (Denmark)

    Maspero, Jorge; Backer, Vibeke; Yao, Ruji

    2014-01-01

    BACKGROUND: Associations of inhaled corticosteroids (ICS) with bone mineral density (BMD) loss have not been characterized consistently. OBJECTIVE: This randomized, double-blind study assessed effects of mometasone furoate (MF) administered via dry powder inhaler on BMD of patients with persisten...

  19. Twelve-week efficacy and safety study of mometasone furoate/formoterol 200/10 microg and 400/10 microg combination treatments in patients with persistent asthma previously receiving high-dose inhaled corticosteroids

    DEFF Research Database (Denmark)

    Weinstein, Steven F; Corren, Jonathan; Murphy, Kevin

    2010-01-01

    A significant unmet medical need exists in patients with uncontrolled asthma. The purpose of this study was to evaluate the efficacy and safety of mometasone furoate/formoterol (MF/F) 400/10 microg versus MF 400 microg administered twice-daily (b.i.d.) via metered-dose inhaler in patients...... with asthma uncontrolled on high-dose inhaled corticosteroids (ICS). In a 12-week, randomized, multicenter, double-blind, parallel-group study, patients (>or=12 years of age) were randomized to MF/F 200/10 microg, MF/F 400/10 microg, or MF 400 microg, b.i.d. after a 2- to 3-week open-label run in with MF 400...... microg b.i.d. The primary end point was mean change in area under the curve from 0 to 12 hours in forced expiratory volume in 1 second (FEV(1) AUC(0-12h)) from baseline to week 12 for MF/F 400/10 microg versus MF 400 microg. Effects of MF/F on asthma control and symptoms were evaluated and adverse events...

  20. 21 CFR 524.1610 - Orbifloxacin, mometasone furoate monohydrate, and posaconazole suspension.

    Science.gov (United States)

    2010-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL.... 000061 in § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1) Amount. For dogs weighing less than 30 lbs. instill 4 drops once daily into the ear canal. For dogs weighing 30 lbs. or more, instill...

  1. Induction of interleukin-6 by ionizing radiation in a human epithelial cell line. Modulation by corticosteroids

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    Beetz, A.; Oppel, T.; Lu-Hesselmann, J.; Peter, R.U. [Federal Armed Forces Medical Academy, Munich (Germany). Institute of Radiobiology; Messer, G.; Kind, P.; Peter, R.U. [Munich Univ., Ludwig-Maximilians (Germany). Dept. of Dermatology

    1997-03-01

    To overcome the detrimental effects of an uncontrolled rise of pro-inflammatory cytokines as an acute response to ionizing radiations, therapeutic drugs capable of inhibiting the pathway leading to transcriptional activation of cytokine genes are of particular interest. Here is described the potency of hydrocortisone, dexamethasone and mometasone furoate to inhibit radiation-induced IL-6 (interleukin) expression. Mometasone furoate and dexamethasone were shown to be much more effective than hydrocortisone. Finally, the reported low atrophogenic potential of mometasone furoate after topical application, together with the strongest capacity of IL-6 down-regulation in ionizing radiations treated cells points to this drug as the most promising derivative of the three investigated corticosteroids. (N.C.)

  2. COMPARATIVE STUDY OF TOPICAL MOMETASONE FUROATE 0.1%, TOPICAL 0.03% TACROLIMUS, TOPICAL BASIC FIBROBLAST GROWTH FACTOR (bFGF IN CHILDHOOD VITILIGO

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    Kavitha S. B

    2017-08-01

    Full Text Available BACKGROUND Vitiligo, the commonest of all pigmentary disorders, is an idiopathic, acquired cutaneous achromia, characterised by circumscribed, chalky white macules. It may also involve the pigment epithelium of the eyes, the inner ear and the leptomeninges. Although, vitiligo can begin at any age, it develops before the age of 20 years in 50% of the patients and before the age of 10 years in 25% of patients. MATERIALS AND METHODS The study was conducted for a period of one year with 6 months active intervention. A group of 60 consecutive children attending the outpatient Department of Dermatology were included in this study. The same patients were acting as controls. RESULTS Grade 4 response was seen in 12 cases (60% who were on mometasone (VV-20%, focal-30%, segmental-10%, in 10 cases (50% on tacrolimus (VV-20%, focal-30% and in 4 cases (20% on bFGF (focal. Lesions on the face and neck showed grade 4 response in 16 cases (mometasone-8, tacrolimus-6 and bFGF-2, extremities in 6 cases. On the whole grade, 4 response was observed more with mometasone (60% followed by tacrolimus (50%. Grade 3 response was observed with bFGF (30%. CONCLUSION Topical mometasone was very effective among the 3 drugs used in childhood vitiligo showing grade 4 repigmentation in all types of vitiligo except mucosal vitiligo. Tacrolimus proved almost as effective as mometasone to restore skin colour in lesions of vitiligo in children. Because it does not produce atrophy or other adverse effects, tacrolimus may be very useful for younger patients, and for sensitive areas of the skin such as eyelids, it should be considered in other skin disorders currently treated with topical steroids for prolonged periods. Topical basic fibroblast growth factor though less effective than mometasone and tacrolimus, but can be tried as initial therapy in resistant cases such as segmental vitiligo as initial therapy of small vitiligo patches when physicians may not like to initiate high risk

  3. Study Of Topical Anti-Inflammatory Potency And Clinical Efficacy Of Formulations Of Mometasone And Betamethasone By Cutaneous Blood Flow Measurements In Psoriatic Patients Using Laser Doppler Velocimetry

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    Mulekar S. V

    1997-01-01

    Full Text Available Laser Doppier Velocimetry (LDV was used to measure cutaneous blood flow (CBF in psoriatic skin lesions to assess the effect of once daily application of Mometasone furoate (MF in a base claimed to possess a “reservoir” effect, as against Betamethasone-17-valarate (BV in a conventional cream base, applied twice daily, for 4 weeks. Bilaterally symmetrical active lesions were studied in 10 psoriatics, at baseline and at the end of 2 and 4 weeks’ treatment. The formulations were also evaluated for topical anti-inflammatory potency in terms of their ability to inhibit the Post-Ischaemic-Reactive-Hyperaemic-Response (PIRHR induced on normal uninvolved skin treated under occlusion. The lesions were also assessed subjectively for clinical Psoriatic Hyperaemia Index (PHI = CBF on lesions/CBF on uninvolved skin: 8.42 + 1.74 & 10.13 + 1.70 correlating with high CPI (9 + 0.50 & 9.1 + 0.51. During treatment with MF or BV, the lesions resolved rapidly, with a concomitant decrease in PHI and CPI (Week 2 : PHI = 3.40 + 0.46 & 5.19 + 1.65, CPI = 4.15 + 0.86& 5.20 + 0.87 and Week 4 : PHI = 1.99 + 0.23 & 2.81 + 0.74 CPI = 2.00 + 0.50 & 2.88 + 0.72 respectively. The two formulations Inhibited PIRHR to same extent (auc/min: Control = 1871 + 399.22, MF = 536.11 + 153.34 & BV = 567.5 + 110.76, indicating equal potency. The results show that pharmaceutical factor such as vehicle can significantly influence the clinical efficacy of corticoids.

  4. Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial

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    Tashkin DP

    2012-02-01

    Full Text Available Donald P Tashkin1, Dennis E Doherty2, Edward Kerwin3, Carlos E Matiz-Bueno4, Barbara Knorr5, Tulin Shekar5, Sibabrata Banerjee5, Heribert Staudinger51David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, 3Clinical Research Institute of Southern Oregon, Medford, OR USA; 4Fundación Salud Bosque, Bogota, Colombia; 5Merck Sharp & Dohme Corp, Whitehouse Station, NJ USABackground: A clinical trial of mometasone furoate/formoterol fumarate (MF/F administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD investigated the efficacy and safety of a fixed-dose combination of MF/F.Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 second (FEV1 over 0–12 hours (AUC0–12 FEV1 with MF/F versus MF, and in morning predose FEV1 with MF/F versus F. Key secondary endpoints were quality of life (Saint George’s Respiratory Questionnaire [SGRQ], symptom-free nights, and partly stable COPD at 26 weeks, as well as time to first COPD exacerbation.Results: Significant improvements in FEV1 AUC0–12 occurred at endpoint with MF/F 400/10 and MF/F 200/10 versus MF 400 (P ≤ 0.007. Significant bronchodilation occurred in 5 minutes with MF/F, and serial spirometry demonstrated sustained FEV1 improvements with MF/F over the treatment period. Significant improvements in morning predose FEV1 occurred with both MF/F doses, and these effects were further investigated by excluding results for subjects whose morning FEV1 data were collected >2 days after the last

  5. Fluticasone furoate and vilanterol inhalation powder for the treatment of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Matera, Maria Gabriella; Capuano, Annalisa; Cazzola, Mario

    2015-02-01

    Fluticasone furoate/vilanterol (FF/VI) is a novel inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) fixed dose combination that, by simplifying the dosing schedule, allows, for the first time in a member of the ICS/LABA class, a shift from twice-daily to once-daily treatment. FF/VI is delivered via a novel, single-step activation, multi-dose dry powder inhaler for oral inhalation, Ellipta. Regrettably, there are no head-to-head trials that have shown superiority in the safety or efficacy of FF versus other ICSs, but evidence shows that VI has a quicker onset of effect versus salmeterol. However, the clinical utility of this effect in a maintenance medication is still questionable. Furthermore, benefits of FF/VI over twice-daily ICS/LABA comparator have not been shown yet and, in addition, its adverse event profile is generally consistent with the known class effects of an ICS/LABA fixed dose combination. In particular, there is an increase in the risk of pneumonia among patients treated with FF/VI relative to VI, mainly among those who benefit most from FF/VI. Nevertheless, the interesting pharmacological profiles of both FF and VI, the possibility that FF/VI can be administered once-daily, and the attractive characteristics of Ellipta are important features that could help FF/VI to be a successful combination in the treatment of chronic obstructive pulmonary disease.

  6. Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications.

    Science.gov (United States)

    Derendorf, H; Meltzer, E O

    2008-10-01

    Intranasal corticosteroids (INSs) are effective treatments for allergic rhinitis, rhinosinusitis, and nasal polyposis. In recent years, increased understanding of corticosteroid and glucocorticoid receptor pharmacology has enabled the development of molecules designed specifically to achieve potent, localized activity with minimal risk of systemic exposure. Pharmacologic potency studies using affinity and other assessments have produced similar rank orders of potency, with the most potent being mometasone furoate, fluticasone propionate, and its modification, fluticasone furoate. The furoate and propionate ester side chains render these agents highly lipophilic, which may facilitate their absorption through nasal mucosa and uptake across phospholipid cell membranes. These compounds demonstrate negligible systemic absorption. Systemic absorption rates are higher among the older corticosteroids (flunisolide, beclomethasone dipropionate, triamcinolone acetonide, and budesonide), which have bioavailabilities in the range of 34-49%. Studies, including 1-year studies with mometasone furoate, fluticasone propionate, and budesonide that evaluated potential systemic effects of INSs in children have generally found no adverse effects on hypothalamic-pituitary-adrenal axis function or growth. Clinical data suggest no significant differences in efficacy between the INSs. Theoretically, newer agents with lower systemic availability may be preferable, and may come closer to the pharmacokinetic/pharmacologic criteria for the ideal therapeutic choice.

  7. Long-term maintenance therapy for vulvar lichen sclerosus: the results of a randomized study comparing topical vitamin E with an emollient.

    Science.gov (United States)

    Virgili, Annarosa; Minghetti, Sara; Borghi, Alessandro; Corazza, Monica

    2013-04-01

    The chronic and relapsing nature of vulvar lichen sclerosus (VLS) represents a challenge for its long-term management after an effective treatment with topical corticosteroids. To compare the effect of topical vitamin E with that of an emollient in reducing the risk of VLS relapse over a 52-week maintenance treatment. 156 patients with VLS were enrolled in a 12-week active treatment phase on topical 0.1% mometasone furoate ointment once daily. Those who achieved disease remission entered a 52-week maintenance phase in which patients were randomized to apply either an emollient or topical vitamin E once daily. 80 patients entered the maintenance phase. At 52 weeks, for the vitamin E maintenance group, the cumulative crude relapse rate was 27.8% and the cumulative modified crude relapse rate was 55.6%. For the emollient maintenance group, the cumulative crude relapse rate was 22.7% and the cumulative modified crude relapse rate was 50.0%. The median time to relapse was 20 weeks for the vitamin E group and 18.7 weeks for the emollient group. Once VLS has been stabilized with topical corticosteroids, long-term treatment with both vitamin E and emollients may be considered in maintain LS remission.

  8. Treatment of streptococcal pharyngitis with once-daily compared with twice-daily amoxicillin: a noninferiority trial.

    Science.gov (United States)

    Clegg, Herbert W; Ryan, Amy G; Dallas, Steven D; Kaplan, Edward L; Johnson, Dwight R; Norton, H James; Roddey, Oliver F; Martin, Edward S; Swetenburg, Raymond L; Koonce, Elizabeth W; Felkner, Mary M; Giftos, P Michael

    2006-09-01

    Two relatively small previous studies comparing once-daily amoxicillin with conventional therapy for group A streptococcal (GAS) pharyngitis reported similar rates of bacteriologic success for each treatment group. The purpose of this study was to further evaluate once-daily amoxicillin for GAS pharyngitis in a larger study. In a single pediatric practice, from October through May for 2 consecutive years (2001-2003), we recruited children 3 to 18 years of age who had symptoms and signs suggestive of GAS pharyngitis. Patients with a positive rapid test for GAS were stratified by weight (or=40 kg) and then randomly assigned to receive once-daily (750 mg or 1000 mg) or twice-daily (2 doses of 375 mg or 500 mg) amoxicillin for 10 days. We determined bacteriologic failure rates for GAS in the pharynx from subsequent swabs taken at 14 to 21 (visit 2) and 28 to 35 (visit 3) days after treatment initiation. We conducted a randomized, controlled, investigator-blinded, noninferiority trial to evaluate whether amoxicillin given once daily would have a bacteriologic failure rate no worse than that of amoxicillin given twice daily within a prespecified margin of 10%. GAS isolates were characterized to distinguish bacteriologic failures from new acquisitions. Adverse events were described and adherence was evaluated by review of returned daily logs and dosage bottles. Of 2139 potential study patients during the 2-year period, we enrolled 652 patients, 326 into each treatment group. Children in the 2 groups were comparable with respect to all demographic and clinical characteristics except that children <40 kg more often presented with rash in each treatment group. At visit 2, failure rates were 20.1% (59 of 294) for the once-daily group and 15.5% (46 of 296) for the twice-daily group (difference, 4.53%; 90% confidence interval [CI], -0.6 to 9.7). At visit 3, failure rates were 2.8% (6 of 216) for the once-daily group and 7.1% (16 of 225) for the twice-daily group (difference, -4

  9. Detemir as a once-daily basal insulin in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Nelson SE

    2011-08-01

    Full Text Available Scott E NelsonCleveland Family Medicine, Cleveland, Mississippi, USABackground: Insulin detemir, a long-acting basal insulin analog, is labeled for once-daily or twice-daily dosing in patients with type 1 (T1DM or type 2 (T2DM diabetes mellitus. Protocols for some earlier clinical studies of detemir evaluated twice-daily dosing, which may have generated the misperception that detemir should be prescribed twice daily for most patients. This review examines pharmacokinetic and pharmacodynamic (PK/PD, observational, and controlled studies that have evaluated once-daily and twice-daily detemir in patients with T2DM to determine the efficacy and safety of once-daily dosing.Methods: PubMed was searched using the keywords “detemir,” “once daily,” “twice daily,” and “type 2 diabetes” with the limits of clinical trial, human, and English.Results: Detemir has a relatively flat time–action profile and duration of action of up to 24 hours for patients with T2DM. Once-daily dosing is the most commonly used detemir regimen reported in observational studies, and controlled clinical studies indicate that once-daily dosing controls glycosylated hemoglobin when detemir is administered alone or in combination with a prandial insulin or oral antidiabetes drugs. In comparative clinical trials, detemir had a similar time–action profile and duration of action to another long-acting insulin analog, glargine, with less within-subject variability. Once-daily detemir was associated with no weight gain or less weight gain than comparator regimens. For patients who had not achieved glycemic control with a basal dose of once-daily detemir, adding a prandial insulin provided better glycemic control, less postprandial hypoglycemia, and a lower total daily dose of detemir than twice-daily detemir. Involvement of a multidisciplinary team and the use of a holistic approach for the treatment of T2DM patients are recommended to achieve and maintain the best

  10. Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu

    2013-10-15

    Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.

  11. Once- versus twice-daily aspirin treatment in patients with essential thrombocytosis

    DEFF Research Database (Denmark)

    Larsen, Mads Lamm; Pedersen, Oliver Heidmann; Hvas, Anne-Mette

    2018-01-01

    Insufficient platelet inhibition has been reported in up to 40% of aspirin-treated patients, including patients with essential thrombocytosis. To maintain sufficient platelet inhibition, a shorter dosing interval with aspirin has been suggested. We aimed to investigate the antiplatelet effect...... of low-dose aspirin given twice-daily compared to standard once-daily dosing in patients with essential thrombocytosis. We included 22 patients, who were treated for 7 days with standard once-daily aspirin (75 mg once-daily) followed by 7 days treatment of twice-daily aspirin (37.5 mg twice......-daily). The two regimens were separated by 14 days aspirin washout. Blood samples were obtained 1h and 24h/12h after the last pill intake in each regimen. The effect of aspirin was evaluated by: (1) platelet aggregation measured by whole blood impedance aggregometry (Multiplate® Analyser) using arachidonic acid...

  12. Cerebrospinal fluid abacavir concentrations in HIV-positive patients following once-daily administration.

    Science.gov (United States)

    Calcagno, A; Pinnetti, C; De Nicolò, A; Scarvaglieri, E; Gisslen, M; Tempestilli, M; D'Avolio, A; Fedele, V; Di Perri, G; Antinori, A; Bonora, S

    2018-06-01

    Abacavir is a widely used nucleotide reverse transcriptase inhibitor, for which cerebrospinal fluid (CSF) exposure has been previously assessed in twice-daily recipients. We studied abacavir CSF concentrations in 61 and nine HIV-positive patients taking abacavir once daily and twice daily, respectively. Patients on once-daily abacavir had higher plasma and CSF concentrations (96 vs. 22 ng ml -1 , P = 0.038 and 123 vs. 49 ng ml -1 , P = 0.038) but similar CSF-to-plasma ratios (0.8 vs. 0.5, P = 0.500). CSF abacavir concentrations were adequate in patients receiving once-daily treatment. © 2018 The British Pharmacological Society.

  13. Once-Daily Radiation Therapy for Inflammatory Breast Cancer

    International Nuclear Information System (INIS)

    Brown, Lindsay; Harmsen, William; Blanchard, Miran; Goetz, Matthew; Jakub, James; Mutter, Robert; Petersen, Ivy; Rooney, Jessica; Stauder, Michael; Yan, Elizabeth; Laack, Nadia

    2014-01-01

    Purpose: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. Methods and Materials: A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof were assessed. Results: Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). Conclusions: Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC

  14. Efficacy and safety of fluticasone furoate/vilanterol or tiotropium in subjects with COPD at cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Covelli H

    2015-12-01

    Full Text Available Henry Covelli,1 Bonavuth Pek,2 Isabelle Schenkenberger,3 Catherine Scott-Wilson,4 Amanda Emmett,5 Courtney Crim4 1Kootenai Health, Coeur d’Alene, ID, USA; 2Clinique de Pneumologie et de Sommeil de Lanaudière, Quebec, Canada; 3Klinische Forschung, Berlin, Germany; 4GlaxoSmithKline Inc., Research Triangle Park, 5PAREXEL International, Durham, NC, USA Background: Fluticasone furoate/vilanterol (FF/VI is a novel, once-daily, inhaled corticosteroid/long-acting β2-agonist combination approved for the treatment of COPD and asthma. We compared the safety and efficacy of FF/VI and tiotropium (TIO in subjects with moderate-to-severe COPD with greater risk for comorbid cardiovascular disease (CVD.Methods: This randomized, blinded, double-dummy, parallel-group study compared a once-daily morning dose of FF/VI 100/25 mcg delivered via ELLIPTA™ with TIO 18 mcg via HandiHaler® for 12 weeks in subjects with diagnosed COPD, forced expiratory volume in 1 second (FEV1 30%–70% predicted, and CVD or CVD risk. The primary endpoint was change from baseline in 24-hour weighted mean FEV1 on Day 84. Other efficacy endpoints included time to onset of bronchodilation, trough FEV1, other spirometry measures, rescue medication use, symptoms, quality of life (St George’s Respiratory Questionnaire-COPD [SGRQ-C], and health status (COPD Assessment Tests [CAT] measures. Safety endpoints included cardiovascular monitoring, cortisol excretion, COPD exacerbations, and adverse events, including prespecified drug effects.Results: Both FF/VI and TIO improved the 24-hour weighted mean FEV1 from baseline after 12 weeks with no significant difference between treatments. Other endpoints favored FF/VI for time to onset of bronchodilation, rescue medication use, dyspnea, SGRQ-C and CAT scores, or favored TIO for change from baseline in forced vital capacity and inspiratory capacity. Pneumonia occurred more frequently in the FF/VI group, and two TIO-treated subjects died

  15. Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial

    NARCIS (Netherlands)

    Eron, Joseph J.; Rockstroh, Jürgen K.; Reynes, Jacques; Andrade-Villanueva, Jaime; Ramalho-Madruga, Jose Valdez; Bekker, Linda-Gail; Young, Benjamin; Katlama, Christine; Gatell-Artigas, Jose Maria; Arribas, Jose R.; Nelson, Mark; Campbell, Havilland; Zhao, Jing; Rodgers, Anthony J.; Rizk, Matthew L.; Wenning, Larissa; Miller, Michael D.; Hazuda, Daria; DiNubile, Mark J.; Leavitt, Randi; Isaacs, Robin; Robertson, Michael N.; Sklar, Peter; Nguyen, Bach-Yen; Bloch, M. T.; Hoy, J.; Workman, C.; Madruga, J. V.; Souza, T.; Telles, F. Q.; Zajdenverg, R.; Angel, J.; Montaner, J. S.; Smith, G. H. R.; Trottier, B.; Tamara, J. R.; Velez, J. D.; Gerstoft, J.; Laursen, A. L.; Mathiesen, L.; Katlama, C.; Molina, J. M.; Raffi, F.; Reynes, J.; Yazdanpanah, Y.; Bogner, J. R.; Fatkenheuer, G.; Hartl, H.; Jaeger, H.; Geerlings, S. E.

    2011-01-01

    Twice-daily raltegravir with once-daily tenofovir-emtricitabine is an effective initial antiretroviral regimen for patients with HIV-1. On the basis of pharmacokinetic data suggesting efficacy of once-daily raltegravir and because adherence is often improved with once-daily dosing, we aimed to

  16. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

    Directory of Open Access Journals (Sweden)

    Balk JM

    2015-08-01

    Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

  17. The antianginal efficacy and tolerability of controlled-release metoprolol once daily

    DEFF Research Database (Denmark)

    Egstrup, K; Gundersen, T; Härkönen, R

    1988-01-01

    In a randomized, double-blind, cross-over study treatment with a new controlled-release (CR) preparation of metoprolol, given once daily, was compared with treatment with conventional metoprolol tablets, given twice daily, in 115 patients with stable effort angina pectoris. The patients were...... questionnaire. When all patients were analysed together there were no differences in antianginal efficacy between the two treatment regimens. However, when the group taking 200 mg daily was analysed separately better exercise tolerance was found during metoprolol CR therapy, as measured by onset of chest pain...... and ST-segment change, compared with conventional metoprolol therapy. The two formulations were well tolerated. When given once daily in a total daily dose of 100 mg, the CR preparation induced less adverse effects than the conventional tablets, 50 mg twice daily. It was concluded that the new metoprolol...

  18. Comparison of health care resource utilization and costs among patients with GERD on once-daily or twice-daily proton pump inhibitor therapy

    Directory of Open Access Journals (Sweden)

    Mody R

    2013-04-01

    Full Text Available Reema Mody,1 Debra Eisenberg,2 Likun Hou,2 Siddhesh Kamat,2 Joseph Singer,2 Lauren B Gerson3 1Takeda Pharmaceuticals International Inc, Deerfield, IL, 2HealthCore Inc, Wilmington, DE, 3Stanford University School of Medicine, Stanford, CA, USA Background: The purpose of this study was to assess differences in health care resource utilization and costs associated with once-daily and twice-daily proton pump inhibitor (PPI therapy. Most patients with gastroesophageal reflux disease (GERD achieve symptom control on once-daily PPI therapy, but approximately 20%–30% require twice-daily dosing. Methods: Patients were ≥18 years of age with at least one medical claim for GERD and at least two PPI claims from HealthCore's Integrated Research Database (HIRDSM during 2004–2009. Patients were continuously eligible for 12 months before and after the index date (date of first PPI claim. Based on PPI dosing throughout the post-index period (quantity of medication dispensed/number of days supply, patients were classified as once-daily (dose ≤ 1.5 pills per day or twice-daily (≥1.5 PPI users. Results: The study cohort included 248,386 patients with GERD (mean age 52.8 ± 13.93 years, 56% females of whom 90% were once-daily and 10% were twice-daily PPI users. The Deyo-Charlson Comorbidity Index for once-daily and twice-daily PPI users was 0.70 ± 1.37 and 0.89 ± 1.54, respectively (P < 0.05. More once-daily patients had claims for Barrett's esophagus (5% versus 2%, P < 0.0001 than twice-daily patients. Post-index, higher proportions of twice-daily patients had at least one GERD-related inpatient visit (7% versus 5%, outpatient visit (60% versus 49%, and office visit (48% versus 38% versus once-daily patients (P < 0.0001. Mean total GERD-related health care costs were $2065 ± $6636 versus $3749 ± $11,081 for once-daily and twice-daily PPI users, respectively (P < 0.0001. Conclusion: Patients receiving twice-daily PPI therapy were likely to have more

  19. Effects of corticosteroids on hyposmia in persistent allergic rhinitis.

    Science.gov (United States)

    Catana, Iuliu V; Chirila, Magdalena; Negoias, Simona; Bologa, Ramona; Cosgarea, Marcel

    2013-01-01

    To asses the effects of two topical nasal corticosteroids sprays on hyposmia in patients with persistent allergic rhinitis. The study was a prospective clinical trial and it included twenty four patients with persistent allergic rhinitis (PER) and hyposmia (H). The patients were divided into two groups depending on the type of corticosteroid topical nasal spray treatment: group A, 200 micrograms dose of mometasone furoate (MF) and group B, 110 micrograms dose of fluticasone furoate (FF) both administered in the morning for 4 weeks. The olfactory function of the patients was evaluated with the extended Test battery "Sniffin' Sticks". The visual analogue scale (VAS) was used for the assessment of hyposmia, nasal discharge. The level of the nasal obstruction, before and after the treatment, was evaluated through the anterior rhinomanometry. The comparisons between the two types of topical corticosteroids showed a significant improvement separately between scores of the odor threshold (OT), odor discrimination (OD) and odor identification (OI) and also on the final olfactory score (SDI) before and after 4 weeks of the treatment. The comparisons of the VAS scores pre and post treatment showed a significant improvement in hyposmia and nasal obstruction. The nasal airflow and the nasal discharge scores were improved, but the differences were not statistically significant between the groups. The final statistical analysis found no significant differences between the two patients groups. The study concludes that fluticasone furoate and mometasone furoate have quite the same effects on hyposmia and on the classical symptoms from PER.

  20. Potential benefit of dolutegravir once daily: efficacy and safety

    Directory of Open Access Journals (Sweden)

    Fantauzzi A

    2013-02-01

    Full Text Available Alessandra Fantauzzi,1 Ombretta Turriziani,2 Ivano Mezzaroma11Department of Clinical Medicine, 2Department of Molecular Medicine, Sapienza, University of Rome, Rome, ItalyAbstract: The viral integrase enzyme has recently emerged as a primary alternative target to block HIV-1 replication, and integrase inhibitors are considered a pivotal new class of antiretroviral drugs. Dolutegravir is an investigational next-generation integrase inhibitor showing some novel and intriguing characteristics, ie, it has a favorable pharmacokinetic profile with a prolonged intracellular half-life, rendering feasible once-daily dosing without the need for ritonavir boosting and without regard to meals. Moreover, dolutegravir is primarily metabolized via uridine diphosphate glucuronosyltranferase 1A1, with a minor component of the cytochrome P450 3A4 isoform, thereby limiting drug–drug interactions. Furthermore, its metabolic profile enables coadministration with most of the other available antiretroviral agents without dose adjustment. Recent findings also demonstrate that dolutegravir has significant activity against HIV-1 isolates with resistance mutations associated with raltegravir and/or elvitegravir. The attributes of once-daily administration and the potential to treat integrase inhibitor-resistant viruses make dolutegravir an interesting and promising investigational drug. In this review, the main concerns about the efficacy and safety of dolutegravir as well as its resistance profile are explored by analysis of currently available data from preclinical and clinical studies.Keywords: antiretroviral drugs, HIV-1 integrase, integrase inhibitors, dolutegravir, once daily

  1. Maintenance of heartburn relief after step-down from twice-daily proton pump inhibitor to once-daily dexlansoprazole modified release.

    Science.gov (United States)

    Fass, Ronnie; Inadomi, John; Han, Cong; Mody, Reema; O'Neil, Janet; Perez, M Claudia

    2012-03-01

    Many patients with gastroesophageal reflux disease (GERD) take a proton pump inhibitor (PPI) twice daily to control symptoms. Once-daily dexlansoprazole modified release (MR) has a dual-delayed release formulation, making it attractive for step-down management of patients whose symptoms are well controlled on twice-daily PPIs. We investigated whether step-down to once-daily dexlansoprazole controls heartburn in patients with GERD who were receiving twice-daily PPI therapy. Patients 18 years and older taking a twice-daily PPI for symptom control were enrolled (n = 178) in a single-blind, multicenter study; 163 patients completed the study and 142 patients met criteria for the efficacy analysis. During the 6-week screening and treatment periods, patients recorded the presence of heartburn symptoms twice daily in electronic diaries. Patients' heartburn was considered well controlled if they had an average of 1 symptom or fewer per week during the last 4 weeks of screening and treatment. After screening, qualified patients were switched to masked dexlansoprazole MR 30 mg and placebo for 6 weeks. The primary efficacy end point was the proportion of patients whose heartburn remained well controlled after step-down. GERD-related symptoms and quality of life (QOL) also were evaluated using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) and the PAGI-QOL questionnaires, respectively. After step-down to once-daily dexlansoprazole MR 30 mg, heartburn remained well controlled in 88% of patients (125 of 142). These patients were able to maintain their GERD-related symptom severity and QOL, indicated by marginal changes in the PAGI-SYM and PAGI-QOL total and subscale scores, respectively. Most patients with GERD who take twice-daily PPI to control heartburn are able to successfully step down to once-daily dexlansoprazole 30 mg. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. Once versus twice daily gentamicin dosing for infective endocarditis

    DEFF Research Database (Denmark)

    Buchholtz, Kristine; Larsen, Carsten Toftager; Schaadt, Bente

    2011-01-01

    Objectives: The aim of this randomized study was to investigate the effects of once versus twice daily gentamicin dosing on renal function and measures of infectious disease in a population with infective endocarditis (IE). Methods: Seventy-one IE patients needing gentamicin treatment according...

  3. Twice-daily versus once-daily applications of pimecrolimus cream 1% for the prevention of disease relapse in pediatric patients with atopic dermatitis.

    Science.gov (United States)

    Ruer-Mulard, Mireille; Aberer, Werner; Gunstone, Anthony; Kekki, Outi-Maria; López Estebaranz, Jose Luis; Vertruyen, André; Guettner, Achim; Hultsch, Thomas

    2009-01-01

    The aim of this study is to compare twice-daily and once-daily applications of pimecrolimus cream 1% for prevention of atopic dermatitis relapses in pediatric patients. This multicenter trial enrolled 300 outpatients aged 2 to 17 years, with mild-to-severe atopic dermatitis. The patients were initially treated with twice-daily topical pimecrolimus until complete clearance or for up to 6 weeks (open-label period). Those who achieved a decrease of at least 1 point in the Investigator's Global Assessment score were then randomized to double-blind treatment with pimecrolimus cream 1% either twice daily or once daily for up to 16 weeks. Study medication was discontinued during periods of disease remission (Investigator's Global Assessment = 0). The primary efficacy end point of the double-blind phase was disease relapse (worsening requiring topical corticosteroids or additional/alternative therapy and confirmed by Investigator's Global Assessment score > or = 3 and pruritus score > or = 2). Of the 300 patients enrolled in the study, 268 were randomized to treatment with pimecrolimus cream 1% either twice daily or once daily (n = 134 in each group). The relapse rate was lower in the twice-daily dose group (9.9%) than that in the once-daily dose group (14.7%), but analysis of the time to disease relapse, using a Cox proportional model to adjust for confounding variables, did not show a statistically significant difference between treatment arms (hazard ratio: 0.64; 95% CI: 0.31-1.30). Treatment of active atopic dermatitis lesions with pimecrolimus cream 1% twice daily, followed by the once-daily dosing regimen, was sufficient to prevent subsequent atopic dermatitis relapses over 16 weeks in pediatric patients.

  4. 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

  5. Extended Efficacy of Once-Daily Atomoxetine in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-07-01

    Full Text Available The efficacy of atomoxetine administered once daily (final dose 1.3 +/- 0.3 mg/kg; mean 44.5 mg per day; range 10-80 mg per day in the morning was assessed throughout the day, including evening and early morning, in a total of 197 children, 6 to 12 years of age (71% male, diagnosed with attention-deficit/hyperactivity disorder (ADHD (69% had combined subtype ADHD, and 35% had comorbid oppositional defiant disorder.

  6. ROLE OF INTRANASAL STEROIDAL SPRAY IN SEASONAL ALLERGIC RHINITIS WITH OCULAR SYMPTOMS

    Directory of Open Access Journals (Sweden)

    Vineel Muppidi

    2017-06-01

    Full Text Available BACKGROUND The eye is especially susceptible to the symptoms of allergic rhinitis, itching (pruritus, tearing (epiphora and redness (erythema because it lacks a mechanical barrier that could prevent the deposition of allergens, such as pollen on the conjunctival surface. These ocular symptoms have been described as examples of the type 1 immediate hypersensitivity reaction. A number of recently published clinical studies apparently support the positive effect of intranasal steroidal sprays on ocular allergy symptoms. The aim of the study is to evaluate the role of intranasal steroids in relieving ocular symptoms in allergic rhinitis. MATERIALS AND METHODS 60 subjects who had seasonal allergic rhinitis with ocular symptoms came to Outpatient Department of Chalmeda Anand Rao Hospital in the year 2015-2016. Randomly, each intranasal steroid is given to 12 patients to a total of 60 patients for 4 weeks 2 puffs in each nostril twice daily and the clinical response is observed. RESULTS A subjective improvement in ocular symptoms was observed in 11 of the 12 patients treated with fluticasone furoate, 8 of 12 patients with fluticasone propionate, 7 of the 12 patients with mometasone furoate, 6 of the 12 patients with beclomethasone and 6 of the 12 patients with budesonide. CONCLUSION Intranasal corticosteroids, which are used for seasonal allergic rhinitis with ocular symptoms are effective in controlling of ocular symptoms. Among these, intranasal corticosteroids, which are used for allergic rhinitis, fluticasone furoate is more effective in relieving ocular symptoms in our study.

  7. Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients

    Science.gov (United States)

    Gaber, A. Osama; Alloway, Rita R.; Bodziak, Kenneth; Kaplan, Bruce; Bunnapradist, Suphamai

    2013-01-01

    Background LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. Methods In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. Results Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. Cmax (P=0.0001), Cmax/Cmin ratio (P<0.001), percent fluctuation (P<0.0001), and swing (P=0.0004) were significantly lower and Tmax significantly (P<0.001) longer for LCP-Tacro versus Prograf. AUC24 and Cmin correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. Conclusions Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations. PMID:23715050

  8. Efficacy and safety of once daily low molecular weight heparin (tinzaparin sodium) in high risk pregnancy.

    LENUS (Irish Health Repository)

    Ní Ainle, Fionnuala

    2008-10-01

    Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant treatment of choice for the prevention and treatment of venous thromboembolism during pregnancy. However, previous studies have demonstrated that the pharmacokinetic profiles of LMWH vary significantly with increasing gestation. Consequently, it remains unclear whether LMWH regimens recommended for use in nonpregnant individuals can be safely extrapolated to pregnant women. The aims of this study were to assess the safety and the efficacy of tinzaparin sodium (Innohep) administered only once daily during pregnancy. A systematic retrospective review identified a cohort of 37 high-risk pregnancies which had been managed using tinzaparin 175 IU\\/kg once daily. In 26 cases, the index pregnancy had been complicated by development of an acute venous thromboembolism (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case notes were examined and data extracted using a predetermined questionnaire. No episodes of recurrent venous thromboembolism were identified amongst this cohort of pregnancies managed using once daily LMWH administration. However, two unusual thrombotic complications were observed, including a parietal infarct in one patient, and a postpartum cerebral venous thrombosis in another. Once daily tinzaparin was well tolerated, with no cases of heparin-induced thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin dose modification based upon peak anti-Xa levels occurred in 45% of the cases examined. The present study is the largest study to have examined the clinical efficacy of once daily LMWH for use in pregnant women at high risk of venous thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin at a dose of 175 IU\\/kg. In order to determine whether this once daily regimen provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH regimens during pregnancy will require highly powered

  9. Nasal deposition of ciclesonide nasal aerosol and mometasone aqueous nasal spray in allergic rhinitis patients.

    Science.gov (United States)

    Emanuel, Ivor A; Blaiss, Michael S; Meltzer, Eli O; Evans, Philip; Connor, Alyson

    2014-01-01

    Sensory attributes of intranasal corticosteroids, such as rundown to the back of the throat, may influence patient treatment preferences. This study compares the nasal deposition and nasal retention of a radiolabeled solution of ciclesonide nasal aerosol (CIC-hydrofluoroalkane [HFA]) with a radiolabeled suspension of mometasone furoate monohydrate aqueous nasal spray (MFNS) in subjects with either perennial allergic rhinitis (AR) or seasonal AR. In this open-label, single-dose, randomized, crossover scintigraphy study, 14 subjects with symptomatic AR received a single dose of radiolabeled 74-μg CIC-HFA (37 μg/spray, 1 spray/each nostril) via a nasal metered-dose inhaler or a single dose of radiolabeled 200-μg MFNS (50 μg/spray, 2 sprays/each nostril), with a minimum 5-day washout period between treatments. Initial deposition (2 minutes postdose) of radiolabeled CIC-HFA and MFNS in the nasal cavity, nasopharynx, and on nasal wipes, and retention of radioactivity in the nasal cavity and nasal run-out on nasal wipes at 2, 4, 6, 8, and 10 minutes postdose were quantified with scintigraphy. At 2 and 10 minutes postdose, deposition of radiolabeled CIC-HFA was significantly higher in the nasal cavity versus radiolabeled MFNS (99.42% versus 86.50% at 2 minutes, p = 0.0046; and 81.10% versus 54.31% at 10 minutes, p Deposition of radioactivity on nasal wipes was significantly higher with MFNS versus CIC-HFA at all five time points, and posterior losses of radiolabeled formulation were significantly higher with MFNS at 6, 8, and 10 minutes postdose. In this scintigraphic study, significantly higher nasal deposition and retention of radiolabeled aerosol CIC-HFA were observed versus radiolabeled aqueous MFNS in subjects with AR.

  10. Efficacy and safety of rosuvastatin every other day compared with once daily in patients with hypercholesterolemia.

    Science.gov (United States)

    Wongwiwatthananukit, Supakit; Sansanayudh, Nakarin; Dhummauppakorn, Rawadee; Kitiyadisai, Chutiporn

    2006-11-01

    Although most patients with hypercholesterolemia require life-long therapy with statins, these drugs are underused due to high costs. Every-other-day therapy could be one strategy to resolve this problem. To compare the efficacy and safety of rosuvastatin 10 mg administered every other day versus once daily. An 8 week, randomized, open-label, parallel trial was conducted at the outpatient department of Phramongkutklao Hospital in Bangkok, Thailand. Eighty patients with primary hypercholesterolemia were equally randomized to receive rosuvastatin 10 mg once daily or every other day; 76 patients completed the study. Laboratory data were assessed at baseline and at the end of the study. Low-density lipoprotein cholesterol (LDL-C) levels were reduced by 48% and 39% in the once-daily and every-other-day groups, respectively (p = 0.011). The percentage of patients who achieved LDL-C goals according to National Cholesterol Education Program-Adult Treatment Panel III guidelines was not significantly different between the once-daily (85%) and every-other-day (70%) groups (p = 0.180). In addition, both regimens were well tolerated, with no patient developing an elevation of more than 3 times baseline levels of aspartate aminotransferase or alanine aminotransferase or 10 times that of creatine kinase. As expected, the monthly cost per percent LDL-C reduction of the once-daily (0.72 dollars) regimen was about 38% higher than that of the every-other-day (0.44 dollars) regimen. Every-other-day dosing of rosuvastatin may be an alternative regimen for cost savings, without a major decrease in therapeutic benefit or increase in adverse events, in patients with hypercholesterolemia. The number of patients achieving their LDL-C goal using the every-other-day regimen is comparable with the number using the once-daily regimen, especially in the low-risk patient category.

  11. Efficacy and Safety of Once-Daily Minoxidil Foam 5% Versus Twice-Daily Minoxidil Solution 2% in Female Pattern Hair Loss: A Phase III, Randomized, Investigator-Blinded Study.

    Science.gov (United States)

    Blume-Peytavi, Ulrike; Shapiro, Jerry; Messenger, Andrew G; Hordinsky, Maria K; Zhang, Paul; Quiza, Carlos; Doshi, Uday; Olsen, Elise A

    2016-07-01

    A once-daily minoxidil topical foam (MTF) has been developed to treat female pattern hair loss. Determine noninferiority of once-daily 5% MTF versus twice-daily 2% minoxidil topical solution (MTS) based on the change from baseline in target area hair count (TAHC) at 24 weeks. In a randomized, phase III trial, women with female pattern hair loss received once-daily 5% MTF (n=161) or twice-daily 2% MTS (n=161) for 52 weeks. Primary endpoint was change from baseline in TAHC at 24 weeks. Secondary endpoint was change from baseline in TAHC at 12 weeks. Exploratory endpoints included change in total unit area density and change in overall scalp coverage. Once-daily 5% MTF increased TAHC from baseline (adjusted mean ± standard error) by 23.9 ± 2.1 hairs/cm2 at week 24. Twice-daily 2% MTS increased TAHC 24.2 ± 2.1 hairs/cm2 at week 24. The treatment difference was -0.3 hairs/cm2 (95% CI = -6.0, 5.4). Since the lower bound of the 95% CI was less than -5.0, the prespecified noninferiority goal was not met. Both treatments were well tolerated. Once-daily 5% MTF and twice-daily 2% MTS induced hair regrowth in female pattern hair loss, but prespecified noninferiority criteria were not met. ClinicalTrials.gov identifier: NCT01145625 J Drugs Dermatol. 2016;15(7):883-889.

  12. A dose-finding, placebo-controlled study on extended-release felodipine once daily in treatment of hypertension.

    Science.gov (United States)

    Cambell, L M; Ross, J R; Goves, J R; Lees, C T; McCullagh, A; Barnes, P; Timerick, S J; Richardson, P D

    1989-12-01

    Hypertensive patients received a beta-blocker plus placebo once daily for 4 weeks. If their diastolic blood pressure (DBP) was then 95-115 mm Hg, they were randomized to receive, in addition to the beta-blocker, placebo (n = 36), felodipine-extended release (ER) 10 mg (n = 36), or felodipine-ER 20 mg (n = 37) in a 4-week double-blind parallel-group trial. All medication was administered once daily and, when BP was measured 24 h after the last dose, felodipine-ER 10 mg reduced DBP by 14 +/- 9 mm Hg (mean +/- SD) from a mean of 103 mm Hg and felodipine-ER 20 mg reduced DBP by 18 +/- 9 mm Gg from 101 mm Hg. The reductions in DBP with both doses of felodipine were greater than reductions with placebo (5 +/- 8 mm Hg, from 102 mm Hg--both p less than 0.001). At the end of the study, 21% of patients receiving placebo had a DBP less than or equal to 90 mm Hg. In contrast, 69% of patients receiving felodipine-ER 10 mg and 82% receiving 20 mg attained this level. More than 90% of patients receiving 10 mg felodipine-ER once daily had a reduction in DBP greater than 5 mm Hg 24 h postdose. Felodipine-ER was well tolerated. Felodipine-ER once daily is an effective antihypertensive drug for patients who require therapy in addition to a beta-blocker; the tolerability in this study was good, and a starting dose greater than 10 mg once daily is not indicated.

  13. Effect of sprint training: training once daily versus twice every second day.

    Science.gov (United States)

    Ijichi, Toshiaki; Hasegawa, Yuta; Morishima, Takuma; Kurihara, Toshiyuki; Hamaoka, Takafumi; Goto, Kazushige

    2015-01-01

    This study compared training adaptations between once daily (SINGLE) and twice every second day (REPEATED) sprint training, with same number of training sessions. Twenty physically active males (20.9 ± 1.3 yr) were assigned randomly to the SINGLE (n = 10) or REPEATED (n = 10) group. The SINGLE group trained once per day (5 days per week) for 4 weeks (20 sessions in total). The REPEATED group conducted two consecutive training sessions on the same day, separated by a rest period of 1 h (2-3 days per week) for 4 weeks (20 sessions in total). Each training session consisted of three consecutive 30-s maximal pedalling sets with a 10-min rest between sets. Before and after the training period, the power output during two bouts of 30-s maximal pedalling, exercise duration during submaximal pedalling and resting muscle phosphocreatine (PCr) levels were evaluated. Both groups showed significant increases in peak and mean power output during the two 30-s bouts of maximal pedalling after the training period (P every second day improved OBLA during endurance exercise more than the same training once daily.

  14. Once daily, extended release ciprofloxacin for complicated urinary tract infections and acute uncomplicated pyelonephritis.

    Science.gov (United States)

    Talan, David A; Klimberg, Ira W; Nicolle, Lindsay E; Song, James; Kowalsky, Steven F; Church, Deborah A

    2004-02-01

    We assessed the efficacy and safety of 1,000 mg extended release ciprofloxacin orally once daily vs conventional 500 mg ciprofloxacin orally twice daily, each for 7 to 14 days, in patients with a complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP). In this prospective, randomized, double-blind, North American multicenter clinical trial adults were stratified based on clinical presentation of cUTI or AUP and randomized to extended release ciprofloxacin or ciprofloxacin twice daily. Efficacy valid patients had positive pretherapy urine cultures (105 or greater cFU/ml) and pyuria within 48 hours of study entry. Bacteriological and clinical outcomes were assessed at the test of cure visit (5 to 11 days after therapy) and the late followup visit (28 to 42 days after therapy). The intent to treat population comprised 1,035 patients (extended release ciprofloxacin in 517 and twice daily in 518), of whom 435 were efficacy valid (cUTI in 343 and AUP in 92). For efficacy valid patients (cUTI and AUP combined) bacteriological eradication rates at test of cure were 89% (183 of 206) vs 85% (195 of 229) (95% CI -2.4%, 10.3%) and clinical cure rates were 97% (198 of 205) vs 94% (211 of 225) (95% CI -1.2%, 6.9%) for extended release vs twice daily ciprofloxacin. Late followup outcomes were consistent with test of cure findings. Eradication rates for Escherichia coli, which accounted for 58% of pathogens, were 97% or greater per group. Drug related adverse event rates were similar for extended release and twice daily ciprofloxacin (13% and 14%, respectively). Extended release ciprofloxacin at a dose of 1,000 mg once daily was as safe and effective as conventional treatment with 500 mg ciprofloxacin twice daily, each given orally for 7 to 14 days in adults with cUTI or AUP. It provides a convenient, once daily, empirical treatment option.

  15. Compliance, clinical outcome, and quality of life of patients with stable angina pectoris receiving once-daily betaxolol versus twice daily metoprolol: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Przemyslaw Kardas

    2007-05-01

    Full Text Available Przemyslaw KardasThe First Department of Family Medicine, Medical University of LodzBackground: A randomized, controlled trial was conducted in an outpatient setting to examine the effect of beta-blocker dosing frequency on patient compliance, clinical outcome, and health-related quality of life in patients with stable angina pectoris.Methods: One hundred and twelve beta-blockers-naive outpatients with stable angina pectoris were randomized to receive betaxolol, 20 mg once daily or metoprolol tartrate, 50 mg twice daily for 8 weeks. The principal outcome measure was overall compliance measured electronically, whereas secondary outcome measures were drug effectiveness and health-related quality of life.Results: The overall compliance was 86.5 ± 21.3% in the betaxolol group versus 76.1 ± 26.3% in the metoprolol group (p < 0.01, and the correct number of doses was taken on 84.4 ± 21.6% and 64.0 ± 31.7% of treatment days, respectively (p < 0.0001. The percentage of missed doses was 14.5 ± 21.5% in the once-daily group and 24.8 ± 26.4% in the twice-daily group (p < 0.01. The percentage of doses taken in the correct time window (58.6% vs 42.0%, p = 0.01, correct interdose intervals (77.4% v 53.1%, p < 0.0001, and therapeutic coverage (85.6% vs 73.7%, p < 0.001 were significantly higher in the once-daily group. Both studied drugs had similar antianginal effectiveness. Health-related quality of life improved in both groups, but this increase was more pronounced in the betaxolol arm in some dimensions.Conclusions: The study demonstrates that patient compliance with once-daily betaxolol is significantly better than with twice daily metoprolol. Similarly, this treatment provides better quality of life. These results demonstrate possible therapeutic advantages of once-daily over twice-daily beta-blockers in the treatment of stable angina pectoris.Keywords: patient compliance, quality of life, stable angina pectoris, randomized controlled trial

  16. Mometasone-based triple combination therapy in melasma: Is it really safe?

    Directory of Open Access Journals (Sweden)

    Majid Imran

    2010-01-01

    Full Text Available Background: Kligman′s triple combination formula has been one of the most popular treatment options in melasma over the last three decades. The original Kligman′s formula has been modified in many ways over the years and the most recent modification that has been introduced is a triple combination of 2% hydroquinone, 0.025% tretinoin, and 1% mometasone. The use of this triple combination in patients with melasma has seen a sharp rise over the last few years and with this rampant use the side-effect profile of this triple combination has also come to the fore. Aim : The aim of the present study was to assess the overall safety of the mometasone-based triple combination treatment in the management of melasma. Materials and Methods: This retrospective study was performed on 60 patients of melasma who had used a mometasone-based triple combination treatment for at least 3 weeks anytime in the previous 1 year. The patients were given a preformed questionnaire wherein they assessed the overall effect of the triple combination treatment on their melasma during its use as well as after its withdrawal. The patients were specifically asked about the status of their disease as well as the sun sensitivity of their skin before and after the use of triple combination treatment. In addition, the patients were assessed by a single trained dermatologist for the presence of any adverse effects arising out of the triple combination treatment in the form of telangiectasia, hypertrichosis, acne, skin atrophy, etc. Results: Majority of patients (51.7% had used the combination treatment well beyond the recommended duration. About one-third (36.7% of the patients rated their melasma as worse at the time of filling the questionnaire as compared with their disease before the use of triple combination treatment. On clinical examination, the evidence of steroid side effects was seen in 26 patients (43.3%. Steroid-induced telangiectasia was the commonest finding, seen

  17. Update on the clinical utility of once-daily tacrolimus in the management of transplantation

    Directory of Open Access Journals (Sweden)

    Revollo J

    2015-05-01

    Full Text Available Jane Revollo Department of Pharmacy, Jackson Memorial Hospital, University of Miami Leonard M Miller School of Medicine Miami, FL, USAThe review by Posadas Salas and Srinivas of the clinical utility of once-daily tacrolimus formulations in the management of transplant patients1 was timely and relevant. It is worth noting, however, the data were presented in a way that overlooked several key differences between two distinct once-daily tacrolimus formulations. These formulations differ in bioavailability, Cmax, Tmax, dose required to achieve target trough levels, and time to reach target trough. The specific formulation and dosing information of one product was detailed in this review (described as modified release 4 [MR-4]; Astagraf®, Astellas Pharma Inc., Tokyo, Japan, but no formulation or dosing details were provided for a very different once-daily tacrolimus formulation (LCP-Tacro™; Veloxis Pharmaceuticals A/S, Hørsholm, Denmark for which a thorough review was recently published.2 The latter product is currently approved in Europe and under review by the US Food and Drug Administration in the US. In presenting data in this review, the authors did not identify which product was investigated in each of the studies discussed. This could easily lead to misinterpretation of results or erroneous conclusions, ie, that both once-daily formulations are the same. In fact, a careful parsing of the data clearly demonstrates that they are not equivalent. Misunderstanding of this point could have a potentially serious impact on appropriate dosing, safety, and patient management in the post-transplant setting. Differentiation between the two products is needed to clarify what appear to be conflicting results of the studies presented in this review.View original paper by Posadas Salas and Srinivas

  18. Anti-Inflammatory Effect of IL-37b in Children with Allergic Rhinitis

    Directory of Open Access Journals (Sweden)

    Wenlong Liu

    2014-01-01

    Full Text Available Background. Interleukin-37 (IL-37, a newly described member of IL-1family, functioned as a fundamental inhibitor of innate inflammatory and immune responses, especially its isoform IL-37b. Objective. This study was undertaken to evaluate the expression and regulation of IL-37b in children with allergic rhinitis (AR. Methods. Forty children with AR and twenty-five normal controls were included. The relationship between IL-37b and Th1/2 cytokines production in serum and nasal lavage was examined by enzyme-linked immunosorbent assay (ELISA. Peripheral blood mononuclear cells (PBMCs were purified for in vitro regulation experiment of IL-37b. Intranasal mometasone furoate was given in AR children and IL-37b change after one-month treatment was detected using ELISA. Results. We observed significantly decreased IL-37b expression levels in both serum and nasal lavage compared to controls. IL-37b was negatively correlated with Th2 cytokines. Our results also showed that IL-37b downregulated Th2 cytokine expressed by PBMCs and this modulation was through mitogen-activated protein kinase (MAPK and phosphatidylinositol 3-kinase (PI3K pathway. We also found that intranasal mometasone furoate therapy can promote nasal IL-37b expression. Conclusion. IL-37b may be involved in Th2 cytokine regulation in AR and its expression was related to the efficacy of intranasal steroid therapy.

  19. A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women.

    Science.gov (United States)

    Blume-Peytavi, Ulrike; Hillmann, Kathrin; Dietz, Ekkehart; Canfield, Douglas; Garcia Bartels, Natalie

    2011-12-01

    Although twice-daily application of propylene glycol-containing 2% minoxidil topical solution (MTS) stimulates new hair growth, higher concentrations of minoxidil in a once-daily, propylene glycol-free formulation may improve efficacy and reduce unpleasant side effects. We sought to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia. A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The primary efficacy parameter was change from baseline in nonvellus target area hair count at week 24. Secondary end points included change in nonvellus target area hair width, overall efficacy by global photographic review as assessed by treatment-blinded evaluators and the subject herself, adverse events, and participants' assessment of product aesthetics. After 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants' agreement with "the treatment does not interfere with styling my hair" (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS. Because of differences in the formulations tested, study participants were not blinded to treatment. Once-daily 5% MTF is noninferior and as effective for stimulating hair growth as twice-daily 2% MTS in women with androgenetic alopecia and is associated with several aesthetic and practical advantages. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  20. Gabapentin for once-daily treatment of post-herpetic neuralgia: a review

    Directory of Open Access Journals (Sweden)

    Beal B

    2012-07-01

    Full Text Available Benjamin Beal,1 Tobias Moeller-Bertram,1,2 Jan M Schilling,1 Mark S Wallace11Division of Pain Medicine, Department of Anesthesiology, University of California, 2VA San Diego Healthcare System, San Diego, CA, USAAbstract: Post-herpetic neuralgia is a neuropathic pain syndrome resulting from an insult to the peripheral and central nervous systems caused by the varicella zoster virus. Spontaneous pain may result in the persistent sensation of burning, tingling, or aching and may be associated with thermally or mechanically provoked pain, resulting in hyperalgesia or allodynia. The majority of cases occur in patients over the age of 50 years. Gabapentin is a structural analog of gamma aminobutyric acid that binds to the α2-δ site of voltage-dependent calcium channels and modulates the influx of calcium, with a resulting reduction in excitatory neurotransmitter release. Gabapentin is effective in reducing neuropathic pain due to post-herpetic neuralgia when given at least three times per day, due to its short half-life, resulting in demonstrable fluctuations in plasma levels. Gabapentin has dose-limiting side effects that prevent some patients from achieving therapeutic plasma levels, such as somnolence (27.4%, dizziness (23.9%, and ataxia (7.1%. Gralise™ is a once-daily extended-release formulation of gabapentin that has been developed using AcuForm™ technology. AcuForm is a polymer-based drug delivery system that retains the tablet in the stomach and upper gastrointestinal tract for a sustained period of time. Once-daily dosing has been shown to provide comparable drug exposure with an identical daily dose of the immediate-release formulation when administered three times daily. Participants given Gralise 1800 mg daily had a statistically significant reduction in average daily pain intensity scores compared with placebo, reduced sleep interference due to pain, and a greater percent of participants reporting being much or very much improved on

  1. Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

    Science.gov (United States)

    Shen, Jie; Goodkin, Margot L; Tong, Warren; Attar, Mayssa

    2017-01-01

    Purpose Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed. Methods New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve. Results Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation. Conclusion Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties

  2. Effects of Tadalafil 5 mg Dosed Once Daily in Men with Premature Ejaculation.

    Science.gov (United States)

    Ozcan, Levent; Polat, Emre Can; Onen, Efe; Kocaaslan, Ramazan; Otunctemur, Alper; Cekmen, Mustafa; Eraldemir, Ceyla; Ozbek, Emin

    2017-01-01

    In this study, we evaluated the effect of 5 mg tadalafil once daily in men with premature ejaculation (PE). Thirty married men with lifelong PE and 30 healthy men as control group were included in this study. All the patients received 5 mg tadalafil once a day for a month. The international index of erectile function questionnaire and intravaginal ejaculatory latency times (IELTs) and PE profile were recorded before and after treatment. Plasma samples were collected before and after treatment. The mean baseline IELTs was 40.8 ± 8.1 s in the PE group and 196.5 ± 26.2 s in the control group. After treatment in the PE group, the mean IELTs values showed a statistically significant improvement from the baseline values. At the end of 4 weeks, in the PE group, the mean IELT values showed a statistically significant improvement from the baseline values. Baseline serum nitric oxide (NO) levels were 27.3 ± 1.7 in the PE group and in the 31.1 ± 1.4 healthy control groups. After treatment, NO levels were increased from baseline. We consider that 5 mg tadalafil once daily is safety and effective for the treatment of PE. © 2016 S. Karger AG, Basel.

  3. Drug repurposing from an academic perspective

    DEFF Research Database (Denmark)

    Oprea, Tudor; Bauman, Julie E.; Bologa, Cristian G.

    2011-01-01

    Academia and small business research units are poised to play an increasing role in drug discovery, with drug repurposing as one of the major areas of activity. Here we summarize project status for several drugs or classes of drugs: raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate...... intellectual coverage and issues related to dosing and safety may lead to significant drawbacks. The development of a more streamlined regulatory process worldwide, and the development of precompetitive knowledge transfer systems such as a global healthcare database focused on regulatory and scientific...

  4. Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

    Directory of Open Access Journals (Sweden)

    Shen J

    2017-09-01

    Full Text Available Jie Shen,1 Margot L Goodkin,2 Warren Tong,2 Mayssa Attar3 1Clinical Pharmacology, 2Clinical Development, 3Clinical Pharmacology, Metabolism and Immunology, Allergan plc, Irvine, CA, USA Purpose: Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP, but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed.Methods: New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve.Results: Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans, suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation.Conclusion: Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid

  5. Once-daily use of inhaled corticosteroids: A new regimen in the treatment of persistent asthma

    Directory of Open Access Journals (Sweden)

    Jeffrey Leflein

    2000-01-01

    Strict patient adherence with prescribed anti-inflammatory medication is crucial for obtaining optimal therapeutic benefit for patients with asthma. Despite the proven effectiveness of inhaled corticosteroids, patient adherence to prescribed therapy is often low, resulting in increased patient morbidity. Complex dosing regimens contribute greatly to patient non-adherence. Thus, new once-daily regimens of inhaled corticosteroid treatment have been introduced as means to improve patient adherence and provide optimal therapeutic benefit. In the present review, the complex inflammatory and remodeling processes in asthma and their contributions to the clinical manifestations of the disease will be discussed. Currently available, once-daily inhaled corticosteroid treatment options and the advantages of these therapeutic options in the treatment of persistent asthma also will be discussed.

  6. Biomass Derived Chemicals: Furfural Oxidative Esterification to Methyl-2-furoate over Gold Catalysts

    Directory of Open Access Journals (Sweden)

    Maela Manzoli

    2016-07-01

    Full Text Available The use of heterogeneous catalysis to upgrade biomass wastes coming from lignocellulose into higher value-added chemicals is one of the most explored subjects in the prospective vision of bio-refinery. In this frame, a lot of interest has been driven towards biomass-derived building block molecules, such as furfural. Gold supported catalysts have been successfully proven to be highly active and selective in the furfural oxidative esterification to methyl-2-furoate under mild conditions by employing oxygen as benign oxidant. Particular attention has been given to the studies in which the reaction occurs even without base as co-catalyst, which would lead to a more green and economically advantageous process. The Au catalysts are also stable and quite easily recovered and represent a feasible and promising route to efficiently convert furfural to methyl-2-furoate to be scaled up at industrial level.

  7. TREATMENT OF CHILDREN'S ALLERGIC CONJUNCTIVITIS

    Directory of Open Access Journals (Sweden)

    L.D. Ksenzova

    2008-01-01

    Full Text Available Allergic conjunctivitis is a widely spread disease, which is often accompanied with an allergic rhinitis. According to the up to date recommendations, the treatment of the allergic rhino conjunctivitis is based on 3 key principles: elimination of the allergen, conducting an allergen targeted immunotherapy and pharmacotherapy. The medication treatment of the allergic rhino conjunctivitis should include antihistamines of the 2nd generation and/or intranasal corticosteroids. Their effectiveness was proven with the findings of numerous place controlled surveys; in most cases they are safe. The usage experience of the intranasal formulation of mometasone furoate (Nasonex shows that with a minimal biological availability of the medication and the absence of its influence upon the «hypothalamus–hypophysis–adrenal glands» system and growth of children, mometasone can be a medication of choice to treat children's rhino conjunctivitis.Key words: children, allergic conjunctivitis, treatment.

  8. [Effectiveness of new, once-daily 5-aminosalicylic acid in the treatment of ulcerative colitis].

    Science.gov (United States)

    Lakatos, Péter László; Lakatos, László

    2009-03-01

    5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents is commercially available, including azo-bond pro-drugs such as sulfasalazine, olsalazine and balsalazide, and delayed- and controlled-release forms of mesalazine. In addition, the effectiveness of oral therapy relies on good compliance, which may be adversely affected by frequent daily dosing and a large number of tablets. Furthermore, poor adherence has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine including the unique multi-matrix delivery system and mesalazine granules were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of low pill burden and may contribute to increased long-term compliance and treatment success in clinical practice and might potentially further contribute to a decline in the risk for UC-associated colon cancers. In this systematic review, the authors summarize the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.

  9. Pharmacodynamics and Pharmacokinetics Following Once-Daily and Twice-Daily Dosing of Tiotropium Respimat(®) in Asthma Using Standardized Sample-Contamination Avoidance

    DEFF Research Database (Denmark)

    Beeh, Kai-Michael; Kirsten, Anne-Marie; Dusser, Daniel

    2016-01-01

    BACKGROUND: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat(®) 5 μg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacoki...

  10. Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study

    NARCIS (Netherlands)

    Pratley, Richard E.; Nauck, Michael A.; Barnett, Anthony H.; Feinglos, Mark N.; Ovalle, Fernando; Harman-Boehm, Illana; Ye, June; Scott, Rhona; Johnson, Susan; Stewart, Murray; Rosenstock, Julio; Adamson, K.; Ahmann, A.; Ahn, C. W.; Ajani, D.; Akright, L.; Alwine, L.; Alzohaili, O.; Andrawis, N.; Arbañil Huaman, H.; Arora, S.; Bailey, T.; Barnett, A.; Baron, M.; Barreda Caceres, L.; Barrera, J.; Berg, J.; Bertenshaw, R.; Bode, B.; Bolton, D.; Brito, M.; Brock, S.; Brockmyre, A.; Broker, R.; Brusco, O.; Buynak, R.; Canadas-Zizzias, R.; Canas, G.; Capo, J.; Castillo Gamarra, M.; Cathcart, H.; Catindig, E. A.; Chilka, S.; Cho, Y. W.; Choi, D. S.; Chuck, L.; Cooper, M.; Corder, C.; Hoekstra, J.; Kemp, S.

    2014-01-01

    Background As new members of a drug class are developed, head-to-head trials are an important strategy to guide personalised treatment decisions. We assessed two glucagon-like peptide-1 receptor agonists, once-weekly albiglutide and once-daily liraglutide, in patients with type 2 diabetes

  11. Adherence to and Acceptance of Once-Daily Tacrolimus After Kidney and Liver Transplant: Results From OSIRIS, a French Observational Study.

    Science.gov (United States)

    Cassuto, Elisabeth; Pageaux, Georges P; Cantarovich, Diego; Rostaing, Lionel; Loupy, Alexandre; Roche, Bruno; Duvoux, Christophe; Moreau, Karine; Thervet, Eric; Mazouz, Hakim; Bourhis, Yann; Dharancy, Sébastien; Kessler, Michèle

    2016-10-01

    Adherence to immunosuppressive treatments is a major concern in transplanted patients. This 6-month French observational, longitudinal, prospective study aimed to assess patient adherence to and acceptance of once-daily tacrolimus (Advagraf) initiation in kidney and liver transplant recipients. Data from 1106 patients initiating once-daily tacrolimus during posttransplant follow-up were analyzed. Adherence and acceptance were assessed using self-administered questionnaires at inclusion and at 3 and 6 months. Mean age was 52.4 ± 13.2 years, 61.5% were men. For 94.9% of patients, once-daily tacrolimus was prescribed after switching from twice-daily tacrolimus. At inclusion, 20.9% of patients reported good treatment adherence, 72.0% minor nonadherence, and 7.1% were nonadherent. Mean general acceptance score (range, 0-100) was 77.7 (±24.7). At 3 months, adherence was improved in 21.1%, unchanged in 69.2%, and worsened in 9.7% of patients. Mean general acceptance score was 75.4 (±26.5). General acceptance score was improved in 28.0%, unchanged in 39.4%, and worsened in 32.7% of patients. At 6 months, similar changes in adherence and acceptance were observed. Higher general acceptance score at month 3 was significantly associated with better adherence at month 6. Conversion to once-daily tacrolimus led to an improved rate of adherence at month 3 in more than 20% of patients and a worsened rate of adherence in less than 10% of patients.

  12. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial

    DEFF Research Database (Denmark)

    Bretzel, R.G.; Nuber, U.; Landgraf, W.

    2008-01-01

    BACKGROUND: As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic c...

  13. Feeding motivation and plasma metabolites in pregnant sows fed diets rich in dietary fiber either once or twice daily

    DEFF Research Database (Denmark)

    Jensen, Margit Bak; Pedersen, Lene Juul; Theil, Peter Kappel

    2012-01-01

    in an operant conditioning test, and samples of peripheral blood were taken in a balanced design, at 0900, 1200, 1900, and 0700 h, corresponding to 1, 4, 11, and 23 h after feeding for restricted sows fed once daily. No differences in the feeding motivation were found between the 4 restricted diets at any......, indicating that feeding twice daily reduced feeding motivation during the night compared with feeding once daily. Among restricted-fed sows, plasma concentrations of short-chain fatty acids (SCFA) were greater in sows fed high-fiber diets compared with the control (P = 0.02). Nonesterified fatty acid...... level of fiber in the diet of restrictedly fed sows did not reduce their feeding motivation irrespective of fiber source....

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

    Science.gov (United States)

    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.

  15. Efficacy and Safety of Terbinafine 500 mg Once Daily in Patients with Dermatophytosis.

    Science.gov (United States)

    Babu, P Ravindra; Pravin, A J S; Deshmukh, Gaurav; Dhoot, Dhiraj; Samant, Aniket; Kotak, Bhavesh

    2017-01-01

    Dermatophytosis are the most common fungal infections globally. Terbinafine is considered to have good potency against dermatophytes, but resistance to terbinafine is on the rise. The objective of this study was to evaluate the efficacy and safety of terbinafine 500 mg given once daily in treatment of patients with superficial dermatophytosis. It was a retrospective questionnaire-based survey. Each doctor was given survey questionnaire booklet containing survey forms. Clinical response was graded according to the improvement in the affected lesion. Mycological cure was defined as negative microscopy under potassium hydroxide examination and a negative culture in Sabouraud's dextrose agar. Patients were divided into three groups depending on the duration of therapy, Group A - terbinafine 500 mg for 2 weeks, Group B - terbinafine 500 mg for 4 weeks, and Group C - terbinafine 500 mg for 6 weeks. Total 50 doctors completed the survey involving 440 patients. In Group A, out of 194 patients, 87% ( n = 169) patients showed very good response. In Group B, out of 211 patients, 92% ( n = 194) of the patients showed very good response with >75% improvement in their lesion. In Group C, out of 35 patients, 80% ( n = 30) patients showed very good response. Adverse drug reactions of mild to moderate intensity related to terbinafine were seen in 57 patients. Our survey indicates that terbinafine in a dose of 500 mg given once daily was efficacious and safe in the treatment of patients with dermatophytosis.

  16. Effect of sprint training on resting serum irisin concentration - Sprint training once daily vs. twice every other day.

    Science.gov (United States)

    Tsuchiya, Yoshifumi; Ijichi, Toshiaki; Goto, Kazushige

    2016-04-01

    Exercise twice every other day has been shown to lead to increasing peroxisome proliferator receptor γ coactivator-1α (PGC-1α) expression (up-stream factor of irisin) via lowered muscle glycogen level during second of exercise compared with exercise once daily. This study determined the influence of 4weeks of sprint training (training once daily vs. twice every other day) on the serum irisin concentration. Twenty healthy males (20.9±1.3years) were assigned randomly to either the SINGLE or REPEATED group (n=10 per group). The subjects in the SINGLE group participated in a sprint training session once daily (5days per week), whereas those in the REPEATED group performed two consecutive training sessions on the same day with a 1-h rest between sessions (2-3days per week). Both groups completed 20 training sessions over 4weeks. Each training session consisted of three consecutive 30-s maximal pedaling exercises with a 10-min rest between sets. Blood samples were collected before and after training period (48h after completing the last training session). The serum irisin concentration decreased significantly after training in each group (SINGLE, 338.5±77.8 to 207.6±64.6ng/mL; REPEATED, 329.5±83.9 to 234.2±72.8ng/mL, pevery other day). Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Clinical impact of laboratory error on therapeutic drug monitoring of once-daily tobramycin in cystic fibrosis: Case series

    Directory of Open Access Journals (Sweden)

    William A Prescott

    2014-01-01

    Full Text Available Once-daily dosing intravenous tobramycin is commonly used to treat cystic fibrosis pulmonary exacerbations. Clinicians often utilize historical therapeutic drug monitoring data to individualize the dose among patients who have been treated with tobramycin previously. This case series involves three patients with cystic fibrosis who had supra-therapeutic tobramycin levels despite use of a once-daily dosing that produced therapeutic drug levels during a previous hospital admission, raising questions about the validity of these levels. Investigation into several potential sources of error led to the discovery of an analyzer error in the laboratory. Once the laboratory’s tobramycin analyzer was recalibrated, the reported levels were comparable to historical levels. This case series emphasizes the clinical importance of critically analyzing reported levels, and specifically, the importance of utilizing past therapeutic drug monitoring data, if available, for all patients treated with intravenous tobramycin. If a patient was therapeutic on a similar dose of tobramycin during a previous admission, a dose adjustment may not be necessary, and clinicians should consider repeating levels while pursuing alternative explanations for the discrepant serum levels.

  18. Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

    Science.gov (United States)

    Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

    2017-11-01

    To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (Cmax), and plasma concentrations at the end of the dosing interval (Cτ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80

  19. Efficacy and safety of terbinafine 500 mg once daily in patients with dermatophytosis

    Directory of Open Access Journals (Sweden)

    P Ravindra Babu

    2017-01-01

    Full Text Available Introduction: Dermatophytosis are the most common fungal infections globally. Terbinafine is considered to have good potency against dermatophytes, but resistance to terbinafine is on the rise. Objective: The objective of this study was to evaluate the efficacy and safety of terbinafine 500 mg given once daily in treatment of patients with superficial dermatophytosis. Materials and Methods: It was a retrospective questionnaire-based survey. Each doctor was given survey questionnaire booklet containing survey forms. Clinical response was graded according to the improvement in the affected lesion. Mycological cure was defined as negative microscopy under potassium hydroxide examination and a negative culture in Sabouraud's dextrose agar. Patients were divided into three groups depending on the duration of therapy, Group A – terbinafine 500 mg for 2 weeks, Group B – terbinafine 500 mg for 4 weeks, and Group C – terbinafine 500 mg for 6 weeks. Results: Total 50 doctors completed the survey involving 440 patients. In Group A, out of 194 patients, 87% (n = 169 patients showed very good response. In Group B, out of 211 patients, 92% (n = 194 of the patients showed very good response with >75% improvement in their lesion. In Group C, out of 35 patients, 80% (n = 30 patients showed very good response. Adverse drug reactions of mild to moderate intensity related to terbinafine were seen in 57 patients. Conclusion: Our survey indicates that terbinafine in a dose of 500 mg given once daily was efficacious and safe in the treatment of patients with dermatophytosis.

  20. Changes in body weight, blood pressure and selected metabolic biomarkers with an energy-restricted diet including twice daily sweet snacks and once daily sugar-free beverage

    OpenAIRE

    Nickols-Richardson, Sharon M.; Piehowski, Kathryn E.; Metzgar, Catherine J.; Miller, Debra L.; Preston, Amy G.

    2014-01-01

    BACKGROUND/OBJECTIVES The type of sweet snack incorporated into an energy-restricted diet (ERD) may produce differential effects on metabolic improvements associated with body weight (BW) loss. This study compared effects of incorporating either twice daily energy-controlled dark chocolate snacks plus once daily sugar-free cocoa beverage (DC) to non-chocolate snacks plus sugar-free non-cocoa beverage (NC) into an ERD on BW loss and metabolic outcomes. MATERIALS/METHODS In an 18-week randomize...

  1. Comparison of once-daily versus twice-weekly terbinafine administration for the treatment of canine Malassezia dermatitis - a pilot study.

    Science.gov (United States)

    Berger, Darren J; Lewis, Thomas P; Schick, Anthea E; Stone, Richard T

    2012-10-01

    Terbinafine, an allylamine antifungal, is used in pulsatile dose regimens for superficial mycoses in human medicine. To compare the clinical efficacy of twice-weekly versus once-daily terbinafine administration to determine whether preliminary proof-of-concept evidence exists for pulsatile administration of terbinafine in the treatment of canine Malassezia dermatitis and to determine whether twice-weekly treatment results in fewer clinical and owner-perceived adverse events. Twenty client-owned dogs with Malassezia dermatitis. In this randomized, single-blinded clinical trial, dogs were randomly assigned to receive terbinafine (30 mg/kg) either once daily for 21 days (n = 10) or once daily on two consecutive days per week for six doses (n = 10). On day 0 and day 21, a mean yeast count was calculated from eight anatomical locations via adhesive tape-strip cytology, clinical lesion scores were assigned to the same locations, and owners assessed pruritus using a visual analog scale. There was no significant difference between treatment groups with respect to the reduction in mean yeast count (P = 0.343) and clinical lesion scores (P = 0.887). Pruritus measured by visual analog scale was significantly decreased in the twice-weekly treatment group compared with the daily treatment group (P = 0.047). Seven of 20 dogs had a clinically measurable or owner-reported adverse event during treatment that included gastrointestinal disturbances, excessive panting and elevated hepatic enzymes, with no significant difference noted between treatment groups. This pilot study indicates that twice-weekly terbinafine administration may be an effective alternative treatment for canine Malassezia dermatitis and merits further investigation. © 2012 The Authors. Veterinary Dermatology © 2012 ESVD and ACVD.

  2. Once-daily dosing of saquinavir and low-dose ritonavir in HIV-1-infected individuals: a pharmacokinetic pilot study

    NARCIS (Netherlands)

    van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Lange, J. M.; Beijnen, J. H.; Hoetelmans, R. M.

    2000-01-01

    To investigate the steady-state pharmacokinetics of a once-daily dosing regimen of saquinavir soft gelatin capsules in combination with a low dose of ritonavir in HIV-1-infected individuals. Open-label, multi-dose, pharmacokinetic pilot study. Seven HIV-1-infected individuals who were treated with

  3. A once-daily dose of tadalafil for erectile dysfunction: compliance and efficacy

    Directory of Open Access Journals (Sweden)

    Samuel L Washington III

    2010-08-01

    Full Text Available Samuel L Washington III1, Alan W Shindel21School of Medicine, University of California at San Francisco, San Francisco, California, USA; 2Department of Urology, University of California at San Francisco, San Francisco, California, USAAbstract: Selective phosphodiesterase type 5 inhibitors (PDE5Is have revolutionized the ­treatment of erectile dysfunction (ED in men. As an on-demand treatment, PDE5Is have excellent efficacy and safety in the treatment of ED due to a broad spectrum of etiologies. Nevertheless, these drugs do have side-effect profiles that are troublesome to some patients, eg, headache, dyspepsia, myalgia, etc. Furthermore, many patients and their partners dislike the necessity of on-demand treatment for ED, citing a desire for greater spontaneity with sexual interactions. In 2008, approximately 10 years after the release of the first commercially available PDE5I, a paradigm shift in the management of ED occurred with the approval of once-daily dose of tadalafil by the US Food and Drug Administration for the management of ED. The prolonged half-life of tadalafil lends itself well to this dosing regimen and conveys the advantage of separating medication from sexual interactions; lower dose therapy also carries the theoretical benefit of lower incidence of side effects. In this study, we review the current state of the art with respect to this new management strategy for ED, highlighting published reports of the efficacy and tolerability of the daily dose tadalafil regimen.Keywords: PDE5 inhibitor, on-demand therapy, side effects, daily dosing

  4. An observational study evaluating tacrolimus dose, exposure, and medication adherence after conversion from twice- to once-daily tacrolimus in liver and kidney transplant recipients.

    Science.gov (United States)

    Bäckman, Lars; Persson, Carl-Axel

    2014-03-17

    Immunosuppression regimens in transplantation medicine are complex. Drugs with extended release action have simplified medication dosing without affecting efficacy. This prospective, observational, multicenter study, conducted in a routine medical practice setting, evaluated changes in tacrolimus daily dose and trough levels and patient-reported medication adherence at day 90 after 1:1 (mg: mg) conversion to once-daily tacrolimus in adult liver and kidney transplant recipients. Data from 224 recipients of a liver (n=19) or kidney (n=205) transplant, average age 51±14.5 years, were evaluated. The mean change in tacrolimus daily dose was +0.04 mg/day. Dose remained stable after conversion in 62.5%, was lower in 15.6%, and higher in 22% of patients. Trough level after conversion was lower in 62.6% and higher in 36.5%; generally, levels were 12.8% lower than pre-conversion levels. No acute rejection, graft loss, or serious safety events were observed. Two deaths occurred due to myocardial infarction. Conversion helped 19% to less frequently forget medications and 55% reported no difference in remembering to take the once-daily dose after conversion. The change in dosing frequency was identified as "better" for 55%. Tacrolimus daily dose remained stable while trough levels were significantly lower after conversion to once-daily dosing. Safety and efficacy were maintained; reduced dosing frequency had no apparent influence on patient-reported medication adherence.

  5. Changes of particle size distribution and chemical composition of a hay-based ration offered once or twice daily to dairy cows

    Directory of Open Access Journals (Sweden)

    Roberto Mantovani

    2010-01-01

    Full Text Available The objective of this experiment is to evaluate the changes of particle size distribution and chemical composition of the total mixed ration (TMR based on hay as the main forage component (“dry” TMR and distributed once (7.00 am or twice (7.00 am and 1.00 pm daily to 32 lactating cows. The trial was divided in two periods of 14 days each. Diet (DM=53.7% was formulated in order to assure the nutritional requirements of cows producing 24 kg/d of milk (crude protein=14.4% DM; NDF=40.9% DM; milk FU=0.88/kg DM and additional amounts of concentrates were distributed using automatic feeders. Four TMR samples were collected daily (7.00 am, 10.00 am, 1.00 pm, 4.00 pm for six days during each experiment period for a total number of 48 feed samples. Each feed sample was subjected to the estimation of the particle size distribution using the separator of Pennsylvania State University composed of two sieves (diameters of 19 and 8 mm and a collector on the bottom, and to the determination of the chemical composition. Changes of all three particle size fractions for TMRs were observed during the day with distributions of the TMR both once and twice daily. With the once daily distribution, the large particles fraction increased linearly (P<0.001 from 19.7 to 23.4, 32.2, and 35.1%, while the finest particle fraction decreased (from 60.1 to 58.3, 50.0, 47.8%. According to particle size changes, the chemical composition varied significantly at the different times of sampling when TMR was distributed once daily. Significant variations of DM were detected for TMR with a linear (P<0.001 increase (from 54.4 to 57.9, 60.7, 61.5%. Considering once TMR distribution, the values of NDF and starch showed an opposite trend with an increase of 6.5 and a decrease of 8.3 points from 7.00 am to 4.00 pm (i.e., 9 hrs after distribution. Correlations were estimated between chemical and physical characteristics of TMRs. NDF content was positively and significantly correlated to

  6. Tamsulosin 0.4 mg once daily: effect on sexual function in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction

    NARCIS (Netherlands)

    Höfner, K.; Claes, H.; de Reijke, T. M.; Folkestad, B.; Speakman, M. J.

    1999-01-01

    To evaluate the effect of tamsulosin, 0.4 mg once daily, on sexual function in comparison with placebo and alfuzosin, 2.5 mg three times daily, in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). Data from 830 patients randomized into three European

  7. Once-Daily Tacrolimus Extended-Release Formulation: 1 Year after Conversion in Stable Pediatric Kidney Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Lars Pape

    2011-01-01

    Full Text Available It is speculated that a once-daily dosage of immunosuppression can increase adherence and thereby graft survival. Until now, there have been no studies on once-daily use of Tacrolimus extended-release formulation (TAC-ER in children following pediatric kidney transplantation. In 11 stable pediatric kidney recipients >10 years, efficacy, safety, and tolerability of a switch to TAC-ER were observed over one year. Adherence was determined by use of the BAASIS-Scale Interview and comparison of individual variability of Tacrolimus trough levels. Over the observation period, two acute rejections were observed in one girl with nonadherence and repeated Tacrolimus trough levels of 0 ng/m. Beside this, there were no acute rejections in this trial. TAC dose was increased in 3/11 patients and decreased in 2/11 patients within the course of the study. Six patients did not require a dose adjustment. All but one patient had a maximum of 1 dose change during therapy. Mean Tacrolimus dose, trough levels, and Glomerular filtration rates were also stable. Adherence, as measured by BAASIS-Scale Interview and coefficient of variation of Tacrolimus trough levels, was good at all times. It is concluded that conversion to Tac-ER is safe in low-risk children following pediatric kidney transplantation.

  8. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    S Yu Vorotnikova

    2012-09-01

    Full Text Available Реферат по статье: Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus Juliana Levy, Roberta A Cobas, Marilia B Gomes. Diabetol Metab Syndr. 2010 Mar 18; 2:16.

  9. Once-daily omeprazole/sodium bicarbonate heals severe refractory reflux esophagitis with morning or nighttime dosing.

    Science.gov (United States)

    Orbelo, Diana M; Enders, Felicity T; Romero, Yvonne; Francis, Dawn L; Achem, Sami R; Dabade, Tushar S; Crowell, Michael D; Geno, Debra M; DeJesus, Ramona S; Namasivayam, Vikneswaran; Adamson, Steven C; Arora, Amindra S; Majka, Andrew J; Alexander, Jeffrey A; Murray, Joseph A; Lohse, Matthew; Diehl, Nancy N; Fredericksen, Mary; Jung, Kee Wook; Houston, Margaret S; O'Neil, Angela E; Katzka, David A

    2015-01-01

    Morning dose or twice-daily proton pump inhibitor (PPI) use is often prescribed to heal severe reflux esophagitis. Compare the effect of single dose morning (control arm) versus nighttime (experimental arm) omeprazole/sodium bicarbonate (Zegerid(®)) (IR-OME) on esophagitis and gastroesophageal reflux symptoms. Adult outpatients with Los Angeles grade C or D esophagitis were allocated to open-label 40 mg IR-OME once a day for 8 weeks in a prospective, randomized, parallel design, single center study. Esophagogastroduodenoscopy (EGD) and validated self-report symptom questionnaires were completed at baseline and follow-up. Intention-to-treat and per-protocol analyses were performed. Ninety-two of 128 (72 %) eligible subjects participated [64 (70 %) male, mean age 58 (range 19-86), median BMI 29 (range 21-51), 58 C:34 D]. Overall, 81 (88 %) subjects healed [n = 70 (76 %)] or improved [n = 11 (12 %)] erosions. There was no significant difference (morning vs. night) in mucosal healing [81 vs. 71 %, (p = 0.44)] or symptom resolution [heartburn (77 vs. 65 %, p = 0.12), acid regurgitation (82 vs. 73 %, p = 0.28)]. Prevalence of newly identified Barrett's esophagus was 14 % with half diagnosed only after treatment. Once-daily IR-OME (taken morning or night) effectively heals severe reflux esophagitis and improves GERD symptoms. Results support the clinical practice recommendation to repeat EGD after 8 weeks PPI therapy in severe esophagitis patients to assure healing and exclude Barrett's esophagus.

  10. Feeding motivation and plasma metabolites in pregnant sows fed diets rich in dietary fiber either once or twice daily.

    Science.gov (United States)

    Jensen, M B; Pedersen, L J; Theil, P K; Yde, C C; Bach Knudsen, K E

    2012-06-01

    The present study investigated the effects of source and level of dietary fiber (DF) and feeding frequency (once vs. twice daily) on feeding motivation and plasma metabolites at 4 different time points post feeding. Sixty pregnant sows (Sus scrofa, 4 blocks of 15 sows) were allocated to 1 of 5 diets within blocks. Four diets were restricted (approximately 35 MJ ME/d): a barley and wheat control diet (171 g DF/kg DM; 12 g DF/MJ ME), and 3 fiber diets formulated to contain 35% DF by including pectin residue (323 g DF/kg DM; 25 g DF/MJ ME), potato pulp (404 g DF/kg DM; 29 g DF/MJ ME), or sugar beet pulp (367 g DF/kg DM; 25 g DF/MJ ME). The fifth diet was a mixture including an equal amount of the 3 fiber diets offered semi ad libitum (ad libitum access to feed during 6 periods of 1 h starting at 0300, 0600, 1100, 1500, 1800, and 2300; 354 g DF/kg DM; 25 g DF/MJ ME). The experimental period included 2 periods of 4 wk each. Restricted-fed sows were fed once daily (0800 h) during the first period and twice daily (0800 and 1500 h) during the second period, or vice versa. Semi ad libitum fed sows had access to feed 6 times a day in both periods. In each period, the feeding motivation was assessed in an operant conditioning test, and samples of peripheral blood were taken in a balanced design, at 0900, 1200, 1900, and 0700 h, corresponding to 1, 4, 11, and 23 h after feeding for restricted sows fed once daily. No differences in the feeding motivation were found between the 4 restricted diets at any of the time points post feeding, but semi ad libitum fed sows had a decreased feeding motivation (P motivation at 1900 h (P motivation during the night compared with feeding once daily. Among restricted-fed sows, plasma concentrations of short-chain fatty acids (SCFA) were greater in sows fed high-fiber diets compared with the control (P = 0.02). Nonesterified fatty acid was least in sows on the control diet and greatest in sows on the potato diet, whereas sows on the pectin and

  11. Use of new once-daily 5-aminosalicylic acid preparations in the treatment of ulcerative colitis: Is there anything new under the sun?

    Science.gov (United States)

    Lakatos, Peter Laszlo

    2009-04-21

    5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azobond pro-drugs, as well as delayed- and controlled-release forms of mesalazine. However, poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine, including the unique multi-matrix delivery system and mesalazine granules, were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice. This editorial summarizes the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.

  12. The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in asthma

    OpenAIRE

    Woodcock, Ashley; Bakerly, Nawar Diar; New, John P.; Gibson, J. Martin; Wu, Wei; Vestbo, J?rgen; Leather, David

    2015-01-01

    Background Novel therapies need to be evaluated in normal clinical practice to allow a true representation of the treatment effectiveness in real-world settings. Methods/design The Salford Lung Study is a pragmatic randomised controlled trial in adult asthma, evaluating the clinical effectiveness and safety of once-daily fluticasone furoate (100??g or 200??g)/vilanterol 25??g in a novel dry-powder inhaler, versus existing asthma maintenance therapy. The study was initiated before this investi...

  13. Three-year outcomes of a once daily fractionation scheme for accelerated partial breast irradiation (APBI) using 3-D conformal radiotherapy (3D-CRT)

    International Nuclear Information System (INIS)

    Goyal, Sharad; Daroui, Parima; Khan, Atif J; Kearney, Thomas; Kirstein, Laurie; Haffty, Bruce G

    2013-01-01

    The aim of this study was to report 3-year outcomes of toxicity, cosmesis, and local control using a once daily fractionation scheme (49.95 Gy in 3.33 Gy once daily fractions) for accelerated partial breast irradiation (APBI) using three-dimensional conformal radiotherapy (3D-CRT). Between July 2008 and August 2010, women aged ≥40 years with ductal carcinoma in situ or node-negative invasive breast cancer ≤3 cm in diameter, treated with breast-conserving surgery achieving negative margins, were accrued to a prospective study. Women were treated with APBI using 3–5 photon beams, delivering 49.95 Gy over 15 once daily fractions over 3 weeks. Patients were assessed for toxicities, cosmesis, and local control rates before APBI and at specified time points. Thirty-four patients (mean age 60 years) with Tis 0 (n = 9) and T1N0 (n = 25) breast cancer were treated and followed up for an average of 39 months. Only 3% (1/34) patients experienced a grade 3 subcutaneous fibrosis and breast edema and 97% of the patients had good/excellent cosmetic outcome at 3 years. The 3-year rate of ipsilateral breast tumor recurrence (IBTR) was 0% while the rate of contralateral breast events was 6%. The 3-year disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS) was 94%, 100%, and 100%, respectively. Our novel accelerated partial breast fractionation scheme of 15 once daily fractions of 3.33 Gy (49.95 Gy total) is a remarkably well-tolerated regimen of 3D-CRT-based APBI. A larger cohort of patients is needed to further ascertain the toxicity of this accelerated partial breast regimen

  14. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

    Science.gov (United States)

    Philosophe, Benjamin; Leca, Nicolae; West-Thielke, Patricia M; Horwedel, Timothy; Culkin-Gemmell, Christine; Kistler, Kristin; Stevens, Daniel R

    2018-02-20

    The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  15. Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study.

    Science.gov (United States)

    Pratley, Richard E; Nauck, Michael A; Barnett, Anthony H; Feinglos, Mark N; Ovalle, Fernando; Harman-Boehm, Illana; Ye, June; Scott, Rhona; Johnson, Susan; Stewart, Murray; Rosenstock, Julio

    2014-04-01

    As new members of a drug class are developed, head-to-head trials are an important strategy to guide personalised treatment decisions. We assessed two glucagon-like peptide-1 receptor agonists, once-weekly albiglutide and once-daily liraglutide, in patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs. We undertook this 32-week, open-label, phase 3 non-inferiority study at 162 sites in eight countries: USA (121 sites), Australia (9 sites), Peru (7 sites), Philippines (7 sites), South Korea (5 sites), UK (5 sites), Israel (4 sites), and Spain (4 sites). 841 adult participants (aged ≥18 years) with inadequately controlled type 2 diabetes and a BMI between 20 and 45 kg/m(2) were enrolled and randomised in a 1:1 ratio to receive albiglutide 30 mg once weekly titrated to 50 mg at week 6, or liraglutide 0·6 mg once daily titrated to 1·2 mg at week 1 and 1·8 mg at week 2. The randomisation schedule was generated by an independent randomisation team by the permuted block method with a fixed block size of 16. Participants and investigators were unmasked to treatment. The primary endpoint was change from baseline in HbA1c for albiglutide versus liraglutide, with a 95% CI non-inferiority upper margin of 0·3%. The primary analysis was by modified intention to treat. The study is registered with ClinicalTrials.gov, number NCT01128894. 422 patients were randomly allocated to the albigultide group and 419 to the liraglutide group; 404 patients in the abliglutide group and 408 in the liraglutide group received the study drugs. The primary endpoint analysis was done on the modified intention-to-treat population, which included 402 participants in the albiglutide group and 403 in the liraglutide group. Model-adjusted change in HbA1c from baseline to week 32 was -0·78% (95% CI -0·87 to -0·69) in the albigludite group and -0·99% (-1·08 to -0·90) in the liraglutide group; treatment difference was 0·21% (0·08-0·34; non-inferiority p value=0

  16. Early interventional treatment with intranasal corticosteroids compared with postonset treatment in pollinosis.

    Science.gov (United States)

    Higaki, Takaya; Okano, Mitsuhiro; Makihara, Seiichiro; Fujiwara, Tazuko; Haruna, Takenori; Noda, Yohei; Kariya, Shin; Nishizaki, Kazunori

    2012-12-01

    The usefulness of early interventional treatment (EIT) with intranasal corticosteroids (INSs) compared with postonset treatment (POT) has not been clarified. To study the efficacy and safety of EIT with INSs compared with POT and placebo in Japanese cedar/cypress pollinosis. We designed a 3-armed, double-blinded, randomized, placebo-controlled trial. Patients received mometasone furoate nasal spray (EIT group: n = 25), placebo (n = 25), or 4 weeks of placebo followed by 8 weeks of mometasone (POT group: n = 25) for a 12-week period starting on February 1, 2011. The primary end point was the comparison of the total nasal symptom score (TNSS) among the 3 groups. Total ocular symptom score (TOSS), total naso-ocular symptom score (TSS), Allergic Rhinitis and Its Impact (ARIA) on Asthma classification, and safety were the main secondary end points. The placebo and POT groups, but not the EIT group, had a significant exacerbation of TNSS and TOSS soon after the start of pollen counts being high on consecutive days. The 12-week mean TSS in the EIT group (score, 2.3) was significantly lower than in the placebo (5.0; P INSs is superior to POT in controlling pollinosis. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Bateman Eric D

    2011-04-01

    Full Text Available Abstract Background The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD. Methods In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843 and II (n = 804, patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1/forced vital capacity ratio of ≤70% and FEV1 1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ and time to first moderate or severe COPD exacerbation. Results At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p Conclusion Aclidinium is effective and well tolerated in patients with moderate to severe COPD. Trial registration ClinicalTrials.gov: NCT00363896 (ACCLAIM/COPD I and NCT00358436 (ACCLAIM/COPD II.

  18. 21 CFR 524.1044h - Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension.

    Science.gov (United States)

    2010-04-01

    ... (Pseudomonas spp. [including P. aeruginosa], coagulase-positive staphylococci, Enterococcus faecalis, Proteus mirabilis, and beta-hemolytic streptococci). [66 FR 712, Jan. 4, 2001, as amended at 68 FR 15370, Mar. 31...

  19. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vilsbøll, Tina

    2007-01-01

    properties that are suitable for once-daily dosing. Liraglutide has demonstrated lasting improvement of HbA(1c )levels, weight reduction and improved beta-cell function in patients with Type 2 diabetes mellitus. Liraglutide is well tolerated; the adverse events that are most frequently reported being...... transient nausea and diarrhoea. This article reviews the mechanisms of action and efficacy of liraglutide for the treatment of Type 2 diabetes mellitus. This agent is presently in Phase III clinical development.......The incretin hormones are intestinal peptides that enhance insulin secretion following ingestion of nutrients. Liraglutide is a glucagon-like peptide-1 receptor analogue, which is obtained by derivatising glucagon-like peptide-1 with a fatty acid, providing a compound with pharmacokinetic...

  20. Pharmacokinetics of a once-daily extended-release formulation of pramipexole in healthy male volunteers: three studies.

    Science.gov (United States)

    Jenner, Peter; Könen-Bergmann, Michael; Schepers, Cornelia; Haertter, Sebastian

    2009-11-01

    Pramipexole is a dopamine agonist used in the treatment of Parkinson's disease. The currently available immediate-release (IR) formulation is taken orally 3 times daily. These studies were conducted to evaluate the pharmacokinetic properties of a variety of prototypes for a once-daily extended-release (ER) formulation of pramipexole and to further characterize the prototype whose pharmacokinetics best matched those of the IR formulation. Three Phase I studies were conducted, all in healthy adult men aged food effect. In the third study, steady-state pharmacokinetics of the optimal ER formulation were assessed across a range of pramipexole doses (0.375-4.5 mg/d), including investigation of the food effect at steady state for the highest dose. Tolerability was assessed throughout all studies based on physical examinations, laboratory measurements, and adverse events (AEs). The 3 studies included 18, 15, and 39 subjects, respectively. Among the ER prototypes tested at 0.75 mg once daily in study 1, a matrix tablet had the optimal pharmacokinetic resemblance to IR pramipexole 0.25 mg TID, with a geometric mean AUC(0-24h,ss) of 17.4 ng.h/mL (vs 16.0 ng.h/mL for the IR formulation), C(max,ss) of 0.967 ng/mL (vs 1.09 ng/mL), and C(min,ss) of 0.455 ng/mL (vs 0.383 ng/mL). For single-dose ER 0.375 mg administered in the fasted state in study 2, in vivo bioavailability was predictable from in vitro dissolution data, with internal mean absolute percent prediction errors of 3.18% for AUC(0-30h) and 4.87% for C(max), and external mean absolute prediction errors of 6.61% and 3.34%, respectively, satisfying current guidelines for a level A IVIVC. For single-dose ER 0.375 mg administered in the fed state, the upper bound of the 90% CI for fed:fasted values was 119.8 for AUC(0-30h) (within the bioequivalence limits of 80%-125%) and 134.1 for C(max). At steady state in study 3 (subjects' 5th treatment day), dosing at 0.375 to 4.5 mg in the fasted state was associated with a linear

  1. Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with non-gonococcal urethritis.

    Science.gov (United States)

    Takahashi, Satoshi; Ichihara, Kohji; Hashimoto, Jiro; Kurimura, Yuichiro; Iwasawa, Akihiko; Hayashi, Kenji; Sunaoshi, Kenichi; Takeda, Koichi; Suzuki, Nobukazu; Satoh, Takashi; Tsukamoto, Taiji

    2011-06-01

    To confirm the efficacy of the treatment regimen with oral levofloxacin (LVFX) 500 mg once daily for 7 days for patients with non-gonococcal urethritis (NGU), we evaluated the microbiological and clinical outcomes of the regimen in those patients. We finally evaluated 53 patients with symptomatic NGU and 5 patients with asymptomatic NGU. As a result of microbiological examinations, 19 of the symptomatic patients were diagnosed as having non-gonococcal chlamydial urethritis (NGCU); 13 had non-gonococcal non-chlamydial urethritis (NGNCU), and 21 had urethritis without any microbial detection. Five of the asymptomatic patients were diagnosed as having NGCU. Microbiological cure was achieved in 91% of the 32 patients with symptomatic NGU and in 80% of the 5 patients with asymptomatic NGCU. Clinical cure was obtained in 92% of the 53 patients with symptomatic NGU. The microbiological eradication rate for Chlamydia trachomatis was 92% in 24 patients. As for other organisms, the microbiological eradication rate for Mycoplasma genitalium was 60% in 5 patients and that for Ureaplasma urealyticum was 100% in 10. The microbiological and clinical efficacy of oral LVFX 500 mg once daily for 7 days for the patients with NGU was the same for the azithromycin (AZM) 1,000 mg single dose that we previously reported. The eradication rates of C. trachomatis and U. urealyticum in the treatment regimen with LVFX 500 mg were high enough in the clinical setting; however, for M. genitalium, the rate was relatively inferior to that with AZM.

  2. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vilsbøll, Tina

    2007-01-01

    The incretin hormones are intestinal peptides that enhance insulin secretion following ingestion of nutrients. Liraglutide is a glucagon-like peptide-1 receptor analogue, which is obtained by derivatising glucagon-like peptide-1 with a fatty acid, providing a compound with pharmacokinetic propert...... transient nausea and diarrhoea. This article reviews the mechanisms of action and efficacy of liraglutide for the treatment of Type 2 diabetes mellitus. This agent is presently in Phase III clinical development....... properties that are suitable for once-daily dosing. Liraglutide has demonstrated lasting improvement of HbA(1c )levels, weight reduction and improved beta-cell function in patients with Type 2 diabetes mellitus. Liraglutide is well tolerated; the adverse events that are most frequently reported being...

  3. The influence of the preparations with the glucocorticosteroids and ceramides on the morphological state of the rats’ skin with the nonspecific dermatitis

    Directory of Open Access Journals (Sweden)

    Ya. O. Butko

    2013-04-01

    Full Text Available Introduction. Local therapy is an important method for treatment of dermatitis used to suppress the skin inflammation and the main related symptoms: hyperemia, edema, pruritus, lichenification etc. However today it is important to pay more attention to elimination of the skin dryness, restoration of the damaged epithelium and improvement of the skin barrier functions in dermatitis therapy. Considering all the requirements mentioned above, cream and ointment that correspond to the modern requirements of the local therapy were developed. They promote the decrease of inflammatory processes in skin (Mometasone furoate and Methylprednisolone atseponat are strong GCS with antipruritic, anti-inflammatory, vasoconstrictive, antiproliferative action and with minimum side effects, eliminate excessive skin dryness, restore the damaged epithelium, improve the skin condition and normalize the barrier functions of the skin (ceramides are the natural ceramides of the human’s skin. The purpose of this work was morphological study of the rats’ skin during treatment with cream “Mometasone with ceramides” and ointment “Methyl­prednisolone with ceramides” in the conditions of contact dermatitis inducted by turpentine. Materials and methods. Skin of animals was an object of the research after its treatment with cream “Mometasone with ceramides” and ointment “Methylprednisolone with ceramides”. The comparator preparations were cream “Elocom” and ointment “Advantan”. In the experiment 36 rats divided into groups were used. All the preparations were applied on the skin in a thin layer once a day. After the 5th day of the treatment animals were taken out of the experiment and all the tissue materials were fixed in 10% solution of formalin for morphological studies carrying out. Sections were stained with hematoxylin and eosine. An examination was carried out under the microscope Micros 400. Results of the research. The results showed that

  4. Addition of topical pimecrolimus to once-daily mid-potent steroid confers no short-term therapeutic benefit in the treatment of severe atopic dermatitis; a randomized controlled trial.

    Science.gov (United States)

    Spergel, J M; Boguniewicz, M; Paller, A S; Hebert, A A; Gallagher, P R; McCormick, C; Parneix-Spake, A; Hultsch, T

    2007-08-01

    Combination therapy with pimecrolimus cream 1%, a topical calcineurin inhibitor (TCI), and fluticasone propionate cream 0.05% (FP), a mid-potency topical corticosteroid, may have a synergistic effect for treatment of atopic dermatitis (AD) because their mechanism of action differs. To assess the efficacy of concomitant pimecrolimus twice daily/FP once daily vs. vehicle twice daily/FP once daily in patients with severe AD. An exploratory, 2-week, double-blind, randomized, within-patient study was conducted (n = 45). Two target areas of similar severity, size and location were assessed. Assessments included the modified Eczema Area and Severity Index (0-12 scale) (primary variable), localized investigator global assessment (0-4 scale) and Patients' Self-Assessment of Disease Severity (0-4 scale). Data for all variables were similar for the TCI/FP and vehicle/FP treatments. The efficacy observed for treatment of severe AD flares with this TCI/FP combination regimen was equivalent to that of vehicle/FP.

  5. Comparison of once-daily versus twice-daily dosing of valsartan in patients with chronic stable heart failure

    Directory of Open Access Journals (Sweden)

    Inder S Anand

    2010-06-01

    Full Text Available Inder S Anand1, Anita Deswal2, Dean J Kereiakes3, Das Purkayastha4, Dion H Zappe41Veterans Administration Medical Center, Minneapolis, MN, USA; 2Michael E DeBakey VA Medical Center, Houston, TX, USA; 3The Christ Hospital Heart and Vascular Center, Cincinnati, OH, USA; 4Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; Clinical trial registration information: www.clinicaltrials.gov/ct2/show/NC T00294086 Unique identification number: NC T00294086Background: The safety of once-daily (qd dosing of valsartan in heart failure (HF patients is not known. Hypothesis: This 10-week, double-blind trial examined the relative safety and efficacy of valsartan administered qd versus twice-daily (bid.Methods: HF patients (NYHA class II–III receiving diuretics (87%, angiotensin-converting enzyme inhibitors (98%, beta-blockers (92%, aldosterone antagonists (25%, or digoxin (32% were randomized to valsartan 40 mg bid (n = 60 or 80 mg qd (n = 55 and titrated to a maximum dose of 320 mg/day; doubling the dose every 2 weeks. Clinical and biochemical parameters were measured at Weeks 2, 4, 6, and 10.Results: The average dose of valsartan at the end of study was 245 mg in the bid group vs 256 mg in the qd group (P = NS. Similar proportions of patients tolerated qd vs bid dosing (bid 67% vs qd 68%. Outcome measures including reduction in blood pressure, incidence of hypotension, renal impairment, orthostatic dizziness or fatigue, changes in serum K+, creatinine, cystatin-C, and estimated glomerular filtration rate were similar between the 2 groups at all time-points. Brain natriuretic peptide levels decreased and plasma renin activity increased from baseline by the same amount in both groups at all time-points.Conclusion: Valsartan administered qd has a similar safety and tolerability profile with comparable 24-hour RAAS blockade, as assessed by increases in PRA, as bid dosing in patients with moderate to severe (NYHA class II–III heart failure

  6. Tadalafil once daily in the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in men without erectile dysfunction.

    Science.gov (United States)

    Brock, Gerald; Broderick, Gregory; Roehrborn, Claus G; Xu, Lei; Wong, David; Viktrup, Lars

    2013-11-01

    To assess the safety and efficacy of tadalafil once daily on lower urinary tract symptoms suggestive of clinical benign prostatic hyperplasia (BPH-LUTS) in men without erectile dysfunction (ED). To compare these with effects in men with ED. After a 4-week washout period and 4-week placebo run-in period, 1089 men without ED (n = 338) and with ED (n = 751) were randomly assigned to placebo or tadalafil 5 mg once daily for 12 weeks in three global clinical studies with similar designs. In the pooled dataset, post hoc analyses of covariance assessed the impact and severity of BPH-LUTS using the International Prostate Symptom Score (IPSS) and the BPH Impact Index (BII) and IPSS quality-of-life (IPSS-QoL) subscores. Safety was assessed using treatment-emergent adverse events. The treatment-by-ED-status interaction was used to assess efficacy differences between the with/without ED subgroups. Men without ED were similar in BPH-LUTS severity/previous therapy to men with ED. Tadalafil significantly reduced BPH-LUTS from baseline when compared with placebo in men without ED (IPSS -5.4 vs -3.3, P  0.68). Tadalafil was safe and well tolerated. Tadalafil 5 mg once daily improved BPH-LUTS in men without ED by a magnitude similar to that observed in men with ED. The adverse event profile in men without ED was consistent with that observed in men with ED. © 2013 The Authors. BJU International © 2013 BJU International.

  7. The efficacy and safety of a novel lipophilic formulation of methimazole for the once daily transdermal treatment of cats with hyperthyroidism.

    Science.gov (United States)

    Hill, K E; Gieseg, M A; Kingsbury, D; Lopez-Villalobos, N; Bridges, J; Chambers, P

    2011-01-01

    Previous studies on transdermal methimazole have used pluronic lecithin organogel as the vehicle. This might not be the most suitable vehicle for a lipophilic drug, such as methimazole. Once daily transdermal administration of a novel lipophilic formulation of methimazole is as safe and effective as oral carbimazole in treating hyperthyroidism in cats. Forty-five client-owned cats diagnosed with hyperthyroidism. Prospective study. Cats with newly diagnosed, untreated hyperthyroidism were treated with carbimazole (5 mg p.o., q12h) or methimazole (10 mg) applied to the inner pinnae q24h. Cats were examined after 0, 1, 4, 8, and 12 weeks of treatment. Clinical signs, body weight, systolic blood pressure, hematologic, serum biochemical and urine parameters, total serum thyroxine concentrations (TT4), and serum methimazole concentrations were recorded. No significant differences between groups were detected at day 0. Both formulations were effective in treating hyperthyroidism. No significant differences were detected in thyroxine concentrations, body weight, blood pressure, heart rate, alkaline phosphatase, alanine aminotransferase, creatinine, urea, and urine specific gravity (USG) between groups. The serum methimazole concentrations correlated poorly with TT4-concentrations in both groups. In this 12-week trial, once daily application of a novel formulation of transdermal methimazole applied to the pinnae was as effective and safe as twice daily oral carbimazole in the treatment of cats with hyperthyroidism. This novel formulation and transdermal application could have practical advantages to some pet owners. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  8. Onychomycosis of Toenails and Post-hoc Analyses with Efinaconazole 10% Solution Once-daily Treatment

    Science.gov (United States)

    2016-01-01

    Topical treatment for toenail onychomycosis has been fraught with a long-standing reputation of poor efficaey, primarily due to physical properties of the nail unit that impede drug penetration. Newer topical agents have been formulated as Solution, which appear to provide better therapeutic response in properly selected patients. It is important to recognize the impact the effects that mitigating and concomitant factors can have on efficaey. These factors include disease severity, gender, presence of tinea pedis, and diabetes. This article reviews results achieved in Phase 3 pivotal studies with topical efinaconazole 10% Solution applied once daily for 48 weeks with a focus on how the aforementioned factors influenced therapeutic outcomes. It is important for clinicians treating patients for onychomycosis to evaluate severity, treat concomitant tinea pedis, address control of diabetes if present by encouraging involvement of the patient’s primary care physician, and consider longer treatment courses when clinically relevant. PMID:27047631

  9. PGC-1beta is downregulated by training in human skeletal muscle: no effect of training twice every second day vs. once daily on expression of the PGC-1 family

    DEFF Research Database (Denmark)

    Mortensen, Ole Hartvig; Plomgaard, Peter; Fischer, Christian P

    2007-01-01

    We hypothesized that the peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) family of transcriptional coactivators (PGC-1alpha, PGC-1beta, and PRC) is differentially regulated by training once daily vs. training twice daily every second day and that this difference might...... be observed in the acute response to endurance exercise. Furthermore, we hypothesized that expression levels of the PGC-1 family differ with muscular fiber-type composition. Thus, before and after 10 wk of knee extensor endurance training, training one leg once daily and the other leg twice daily every second...... day, keeping the total amount of training for the legs equal, skeletal muscle mRNA expression levels of PGC-1alpha, PGC-1beta, and PRC were determined in young healthy men (n = 7) in response to 3 h of acute exercise. No significant difference was found between the two legs, suggesting that regulation...

  10. Comparison of therapy augmentation and deviation rates from the recommended once-daily dosing regimen between LDX and commonly prescribed long-acting stimulants for the treatment of ADHD in youth and adults.

    Science.gov (United States)

    Setyawan, Juliana; Hodgkins, Paul; Guérin, Annie; Gauthier, Geneviève; Cloutier, Martin; Wu, Eric; Erder, M Haim

    2013-10-01

    To compare therapy augmentation and deviation rates from the recommended once-daily dosing regimen in Attention Deficit Hyperactivity Disorder (ADHD) patients initiated on lisdexamfetamine (LDX) vs other once-daily Food and Drug Administration (FDA) approved stimulants. ADHD patients initiated on a long-acting ADHD stimulant medication (index medication) in/after 2007 were selected from a large U.S. administrative claims database. Patients were required to be persistent for ≥90 days and continuously enrolled in their healthcare plan for ≥12 months following treatment initiation date. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (≥18 years old), and previously treated adults. Furthermore, patients were classified into four mutually exclusive treatment groups, based on index medication: lisdexamfetamine (LDX), osmotic release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate long-acting (MPH LA), and amphetamine/dextroamphetamine long-acting (AMPH LA). The average daily consumption was measured as the quantity of index medication supplied in the 12-month study period divided by the total number of days of supply. Therapy augmentation was defined as the use of another ADHD medication concomitantly with the index medication for ≥28 consecutive days. Therapy augmentation and deviation rates from the recommended once-daily dosing regimen were compared between treatment groups using multivariate logistic regression models. Compared to the other treatment groups, LDX patients were less likely to augment with another ADHD medication (range odds ratios [OR]; 1.28-3.30) and to deviate from the recommended once-daily dosing regimen (range OR; 1.73-4.55), except for previously treated adult patients, where therapy augmentation differences were not statistically

  11. Comparing omeprazole with fluoxetine for treatment of patients with heartburn and normal endoscopy who failed once daily proton pump inhibitors: double-blind placebo-controlled trial.

    Science.gov (United States)

    Ostovaneh, M R; Saeidi, B; Hajifathalian, K; Farrokhi-Khajeh-Pasha, Y; Fotouhi, A; Mirbagheri, S S; Emami, H; Barzin, G; Mirbagheri, S A

    2014-05-01

    Patients with heartburn but without esophageal erosion respond less well to proton pump inhibitors (PPIs). There is a growing body of evidence implicating the role of psychological comorbidities in producing reflux symptoms. Pain modulators improve symptoms in patients with other functional gastrointestinal disorders. We aimed to compare the efficacy of fluoxetine with omeprazole and placebo to achieve symptomatic relief in patients with heartburn and normal endoscopy who failed once daily PPIs. Endoscopy-negative patients with heartburn who failed once daily PPIs were randomly allocated to receive 6 weeks treatment of fluoxetine, omeprazole, or placebo. Random allocation was stratified according to ambulatory pH monitoring study. Percentage of heartburn-free days and symptom severity was assessed. Sixty patients with abnormal and 84 patients with normal pH test were randomized. Subjects receiving fluoxetine experienced more improvement in percentage of heartburn-free days (median 35.7, IQR 21.4-57.1) than those on omeprazole (median 7.14, IQR 0-50, p heartburn-free days (median improvement, 57.1, IQR 35.7-57.1 vs 13.9, IQR, 0-45.6 and 7.14, 0-23.8, respectively, p heartburn and normal endoscopy who failed once daily PPIs. The superiority of fluoxetine was mostly attributed to those with normal esophageal pH rather than those with abnormal pH (ClinicalTrials.gov, number NCT01269788). © 2014 John Wiley & Sons Ltd.

  12. Postprandial changes in methanogenic and acidogenic bacteria in the rumens of steers fed high- or low-forage diets once daily.

    OpenAIRE

    Leedle, J A; Greening, R C

    1988-01-01

    Four ruminally fistulated Hereford steers (400 kg) were fed two isocaloric diets at 1.5 x maintenance once daily in a repeated measurement crossover experiment. Postprandial changes in hydrogen-oxidizing, carbon dioxide-reducing bacterial groups were monitored. The methanogenic bacterial populations were present at densities of 4 x 10(8) to 8 x 10(8)/g of ruminal contents on either the high- or low-forage diet. Numbers remained constant postprandially on the high-forage diet but showed a dist...

  13. Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli

    2014-01-01

    BACKGROUND AND AIM: Long-acting bronchodilators are the preferred option for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD). The aim of this review is to provide an overview of the clinical studies evaluating the clinical efficacy of the once-daily fixed-dose du...... for chronic Obstructive Lung Disease [GOLD] spirometric criteria). Furthermore, a very recent study has shown that fixed-dose indacaterol/glycopyrronium improves exercise endurance time compared with placebo, although no significant difference was observed between fixed-dose indacaterol...

  14. Tafluprost once daily for treatment of elevated intraocular pressure in patients with open-angle glaucoma

    Directory of Open Access Journals (Sweden)

    Liu Y

    2012-12-01

    Full Text Available Yang Liu, Weiming MaoDepartment of Cell Biology and Anatomy, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TXAbstract: Glaucoma is a leading cause of visual loss worldwide. Current antiglaucoma therapy focuses on lowering intraocular pressure to a safe level. In recent years, prostaglandin analogs have become the first-line agents for treating open angle glaucoma. Tafluprost, which was first reported in 2003, is a novel prostaglandin analog, and has been shown to be a potent ocular hypotensive agent in a number of preclinical and clinical studies. Also, its unique preservative-free formulation helps to decrease preservative-associated ocular disorders and improve patient compliance. In this review, studies from 2003 to 2012 focusing on the structure, metabolism, efficacy, and safety of tafluprost are summarized. These studies suggested that application of tafluprost once daily is a safe and effective treatment for patients with open angle glaucoma.Keywords: tafluprost, prostaglandin analog, glaucoma, intraocular pressure, preservative-free formulation

  15. Accelerated partial breast irradiation using once-daily fractionation: analysis of 312 cases with four years median follow-up

    Directory of Open Access Journals (Sweden)

    Shaikh Arif Y

    2012-02-01

    Full Text Available Abstract Background There are limited data on accelerated partial breast irradiation (APBI using external beam techniques. Moreover, there are recent reports of increased fibrosis and unacceptable cosmesis with APBI using external beam with BID fractionation. We adopted a once daily regimen of APBI with fractionation similar to that shown to be effective in a Canadian randomized trial of whole breast irradiation. It is unclear whether patients with DCIS or invasive lobular carcinoma (ILC are suitable for APBI. Methods The retrospective cohort included 310 patients with 312 tumors of T1-T2N0-N1micM0 invasive ductal carcinoma (IDC, ILC, or Tis (DCIS treated with APBI via external beam. Most patients were treated using IMRT with 16 daily fractions of 270 cGy to a dose of 4320 cGy. The target volume included the lumpectomy cavity plus 1.0 cm to account for microscopic disease and an additional 0.5 to 1.0 cm for setup uncertainty and breathing motion. Ipsilateral breast failure (IBF was pathologically confirmed as a local failure (LF or an elsewhere failure (EF. Results Median follow-up was 49 months. Among the 312 cases, 213 were IDC, 31 ILC, and 68 DCIS. Median tumor size was 1.0 cm. There were 9 IBFs (2.9% including 5 LFs and 4 EFs. The IBF rates among patients with IDC, ILC, and DCIS were 2.4%, 3.2%, and 4.4%, respectively, with no significant difference between histologies. When patients were analyzed by the ASTRO APBI consensus statement risk groups, 32% of treated cases were considered suitable, 50% cautionary, and 18% unsuitable. The IBF rates among suitable, cautionary, and unsuitable patients were 4.0%, 2.6%, and 1.8%, respectively, with no significant difference between risk groups. Acute skin reactions were rare and long-term cosmetic outcome was very good to excellent. Conclusions External beam APBI with once daily fractionation has a low rate of IBF consistent with other published APBI studies. The ASTRO risk stratification did not

  16. Real-world glycemic outcomes in patients with type 2 diabetes initiating exenatide once weekly and liraglutide once daily: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Saunders WB

    2016-07-01

    Full Text Available William B Saunders,1 Hiep Nguyen,2 Iftekhar Kalsekar2 1Department of Public Health Sciences, College of Health and Human Services, The University of North Carolina at Charlotte, Charlotte, NC, 2AstraZeneca, Fort Washington, PA, USA Aim: The glucagon-like peptide-1 receptor agonists exenatide once weekly (QW and liraglutide once daily (QD have demonstrated improvements in glycemic outcomes in patients with type 2 diabetes mellitus in randomized clinical trials. However, little is known about their real-world comparative effectiveness. This retrospective cohort study used the Quintiles Electronic Medical Record database to evaluate the 6-month change in glycated hemoglobin (A1C for patients initiating exenatide QW or liraglutide QD.Methods: Patients with type 2 diabetes mellitus prescribed exenatide QW (n=664 or liraglutide QD (n=3,283 between February 1, 2012 and May 31, 2013 were identified. Baseline A1C measures were from 75 days before to 15 days after initiating exenatide QW or liraglutide QD, with follow-up measures documented at 6 months (±45 days. Adjusted linear regression models compared the difference in mean A1C change. A priori defined sensitivity analysis was performed in the subgroup of patients with baseline A1C ≥7.0% and no prescription for insulin during the 12-month pre-index period.Results: For exenatide QW and liraglutide QD, respectively, mean (SD age of the main study cohort was 58.01 (10.97 and 58.12 (11.05 years, mean (SD baseline A1C was 8.4% (1.6 and 8.4% (1.6, and 48.2% and 54.2% of patients were women. In adjusted models, change in A1C did not differ between exenatide QW and liraglutide QD during 6 months of follow-up. Results were consistent in the subgroup analyses.Conclusion: In a real-world setting, A1C similarly improves in patients initiating exenatide QW or liraglutide QD. Keywords: diabetes, exenatide, outcomes

  17. Action of topical mometasone on the pigmented halos of micrografting in patients with vitiligo Ação da mometasona tópica nos halos pigmentares de microenxertia em vitiligo

    Directory of Open Access Journals (Sweden)

    Karine Dantas Diógenes Saldanha

    2012-10-01

    Full Text Available BACKGROUND: Vitiligo is a prevalent skin pigmentation disorder worldwide. The treatments available still offer limited results to some patients. For patients with clinically stable vitiligo, melanocyte transplantation is an appropriate treatment option, and the technique of autologous punch grafting shows good repigmentation. OBJECTIVE: To evaluate the effect of topical mometasone on the halos of repigmentation after autologous punch grafting in patients with clinically stable vitiligo. METHODS: Between 2009 and 2010, 11 patients with clinically stable vitiligo (7 generalized, 2 focal and 2 segmental underwent autologous punch grafting in the achromic patches. According to the clinical type of vitiligo, patients were instructed to use the corticosteroid ointment during 6 months, only on a few grafted lesions. In the first month, the mometasone ointment was used twice a day and after that just once. They were reassessed 1, 3 and 6 months after the procedure. Grafted halos were photographed and recorded using the software fotofinder. After 6 months, all the treated and untreated areas of the repigmentation halos were measured and analyzed comparatively. RESULTS: The median area of the repigmentation halos after 6 months of treatment with mometasone was larger (25,96 mm² than the one of the untreated halos (13,86 mm² , showing a statistically significant difference (p = 0,026. CONCLUSION: In this study, the use of mometasone ointment increased the area of the repigmentation halos after punch grafting. However, this should be further investigated in larger samples in order to validate this positive action in the treatment of stable vitiligo.FUNDAMENTOS: Vitiligo é um transtorno de pigmentação freqüente na população mundial. Seu tratamento ainda oferece resultados limitados em alguns pacientes. Nos casos de vitiligo estável clinicamente, o transplante de melanócitos tornase uma opção terapêutica, sendo a técnica de enxertos aut

  18. Managing Daily Life

    Science.gov (United States)

    ... Duchenne / Managing Daily Life Print Email Managing Daily Life Environmental accessibility As the person with Duchenne starts ... such as wider doorways and ramps, can make life easier once the person with Duchenne cannot climb ...

  19. Recruitment factors which affect the outcome of a seasonal allergic rhinitis trial.

    Science.gov (United States)

    Sharma, Shilpy; Vasnani, Raj; De Tineo, Marcella; Du, Gaixin; Pinto, Jayant M; Baroody, Fuad M; Naclerio, Robert M

    2011-01-01

    Although intranasal corticosteroids (INSs) are the first-line treatment for seasonal allergic rhinitis (SAR), some patients do not respond adequately, reflecting biological heterogeneity or confounding conditions. The objective of this study was to determine what recruitment factors identify SAR subjects who will be unresponsive to mometasone furoate (MF). We performed a 2-week, double-blind, placebo-controlled, parallel study on 40 subjects with SAR. Each subject underwent a decongestant test using oxymetazoline. Baseline nasal symptoms, nasal peak inspiratory flow (NPIF) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores were recorded. Next, subjects were randomized to either 200 μg of MF or placebo. Symptom diaries and NPIF measurements were completed twice daily. After 2 weeks, subjects repeated the RQLQ and the global assessment of symptoms. There was a significant reduction in symptoms in the MF group compared with placebo (p ≤ 0.05) in patients with baseline total symptom scores of ≥6. Multivariate analysis showed that treatment (MF versus placebo; p = 0.049) and amount of decongestion (percent change in NPIF after oxymetazoline; p = 0.008) predicted the improvement in total nasal symptoms. In clinical trials, SAR subjects must report multiple symptoms to be responsive to treatment with INSs. Our results also support the use of the decongestant test for choice of appropriate study volunteers, both to ensure participation of potentially responsive subjects and to eliminate those with confounding issues.

  20. Pharmacokinetic Comparison of Once-Daily Topical Minocycline Foam 4% vs Oral Minocycline for Moderate-to-Severe Acne.

    Science.gov (United States)

    Jones, Terry M; Ellman, Herman; deVries, Tina

    2017-10-01

    To characterize minocycline pharmacokinetics and relative bioavailability following multiple-dose topical administration of minocycline hydrochloride (HCl) foam 4% (FMX101 4%) as compared with single-dose oral administration of minocycline HCl extended-release tablets (Solodyn®) in subjects with moderate-to-severe acne. A Phase 1, single-center, nonrandomized, open-label, active-controlled, 2-period, 2-treatment crossover clinical study. The study included 30 healthy adults (mean age, 22.6 years; 90% white, and 60% females) who had moderate-to-severe acne. Subjects were assigned to first receive a single oral dose of a minocycline HCl extended-release tablet (approximately 1 mg/kg). At 10 days after the oral minocycline dose, topical minocycline foam 4% was applied, once daily for 21 days. Serial blood samples were obtained before and after administration of oral minocycline and each topical application of minocycline foam 4% on days 1, 12, and 21. Following oral administration of minocycline (approximately 1 mg/kg), plasma minocycline concentration increased until 3 hours, followed by a log-linear decrease over the remainder of the 96-hour sampling period. Following topical application of a 4-g maximal-use dose of minocycline foam 4% for 21 days, plasma minocycline concentration was very low, with geometric mean Cmax values ranging from 1.1 ng/mL to 1.5 ng/mL. Steady state was achieved by day 6. Overall, minocycline exposure with topical minocycline foam 4% was 730 to 765 times lower than that with oral minocycline. There was no evidence of minocycline accumulation over the 21 days of topical application of minocycline foam 4%. Topical minocycline foam 4% appeared to be safe and well tolerated, with no serious treatment-emergent adverse events (TEAEs), treatment-related TEAEs, or TEAEs that led to treatment discontinuation. Once-daily topical application of minocycline foam 4% did not lead to significant systemic exposure to minocycline. It appears to be a well

  1. The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Jeremy A Falk

    2010-04-01

    Full Text Available Jeremy A Falk, Kiran J Philip, Ernst R SchwarzCedars Sinai Women’s Guild Lung Institute, Cedars Sinai Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USAAbstract: Pulmonary hypertension (PH is found in a vast array of diseases, with a minority representing pulmonary arterial hypertension (PAH. Idiopathic PAH or PAH in association with other disorders has been associated with poor survival, poor exercise tolerance, progressive symptoms of dyspnea, and decreased quality of life. Left untreated, patients with PAH typically have a progressive decline in function with high morbidity ultimately leading to death. Advances in medical therapy for PAH over the past decade have made significant inroads into improved function, quality of life, and even survival in this patient population. Three classes of pulmonary artery-specific vasodilators are currently available in the United States. They include prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 (PDE5 inhibitors. In May 2009, the FDA approved tadalafil, the first once-daily PDE5 inhibitor for PAH. This review will outline the currently available data on tadalafil and its effects in patients with PAH.Keywords: PDE-5 inhibition, pulmonary hypertension, tadalafil

  2. Effect of illicit direct to consumer advertising on use of etanercept, mometasone, and tegaserod in Canada: controlled longitudinal study.

    Science.gov (United States)

    Law, Michael R; Majumdar, Sumit R; Soumerai, Stephen B

    2008-09-02

    To assess the impact of direct to consumer advertising of prescription drugs in the United States on Canadian prescribing rates for three heavily marketed drugs-etanercept, mometasone, and tegaserod. Controlled quasi-experimental study using interrupted time series analysis. Representative sample of 2700 Canadian pharmacies and prescription data from 50 US Medicaid programmes. Differences in number of filled prescriptions per 10,000 population per month between English speaking and French speaking (control) Canadian provinces before and after the start of direct to consumer advertising in the United States. Spending on direct to consumer advertising for study drugs ranged from $194m to $314m ( pound104m- pound169m; euro131m-euro212m) over the study period. Prescription rates for etanercept and mometasone did not increase in English speaking provinces relative to French speaking controls after the start of direct to consumer advertising. In contrast, tegaserod prescriptions increased 42% (0.56 prescriptions/10,000 residents, 95% confidence interval 0.37 to 0.76) in English speaking provinces immediately after the start of US direct to consumer advertising. Uncontrolled analysis of US Medicaid data showed a larger 56% increase in tegaserod prescriptions. However, this increase did not persist over time in either country, despite continued advertising. Exposure to US direct to consumer advertising transiently influenced both Canadian and US prescribing rates for tegaserod, a drug later withdrawn owing to safety concerns. The impact of direct to consumer advertising on drug use seems to be highly variable and probably depends on the characteristics of the advertised drug, the level of exposure to direct to consumer advertising, and the cultural context.

  3. Pneumonia risk with inhaled fluticasone furoate and vilanterol compared with vilanterol alone in patients with COPD

    DEFF Research Database (Denmark)

    Crim, Courtney; Dransfield, Mark T; Bourbeau, Jean

    2015-01-01

    : Radiographically confirmed pneumonia risk is increased with inhaled FF/VI, although at less than investigator-defined rates. Modifiable pneumonia risk factors should be considered when attempting to optimize COPD management. Clinical trial registered with www.clinicaltrials.gov (NCT01009463 [HZC102871]; NCT......RATIONALE: Radiographically confirmed pneumonia risk with inhaled corticosteroid use in chronic obstructive pulmonary disease (COPD) has not been assessed to date. OBJECTIVES: To determine the incidence of pneumonia, risk factors, and clinical attributes with inhaled fluticasone furoate (FF...... with compatible parenchymal infiltrates, the respective incidences were 2, 4, 4, and 5%. Factors associated with at least a twofold increase in the risk of pneumonia with FF/VI treatment were being a current smoker, having prior pneumonia, body mass index

  4. Safety and Efficacy of Once-Daily Intravenous Busulfan in Allogeneic Transplantation: A Matched-Pair Analysis.

    Science.gov (United States)

    Kako, Shinichi; Fujiwara, Shinichiro; Sato, Miki; Kimura, Shun-Ichi; Nakasone, Hideki; Ohashi, Kazuteru; Kawakita, Toshiro; Maeda, Tetsuo; Morishita, Takanobu; Suzuki, Ritsuro; Fukuda, Takahiro; Ichinohe, Tatsuo; Kurata, Mio; Atsuta, Yoshiko; Kanda, Yoshinobu

    2018-04-19

    Compared with 4-times-daily infusion of intravenous busulfan (ivBU4), the safety and efficacy of once-daily infusion of ivBU (ivBU1) has not been fully clarified. We have been routinely using ivBU1 in a conditioning regimen in adult patients with myeloid malignancy who undergo allogeneic hematopoietic stem cell transplantation. In this study, a total of 91 patients who received ivBU1 for 2 days (n = 18) or 4 days (n = 73) in our institutions were compared with 273 control patients who received ivBU4, who were matched for age, sex, performance status, disease risk, conditioning regimen, and donor type, selected from the database of the Japanese Society for Hematopoietic Cell Transplantation using optimal matching algorithms. One-year overall survival (56.8% versus 57.1%, P = .94), disease-free survival (51.6% versus 50.8%, P = .73), relapse rate (28.5% versus 26.2%, P = .94), nonrelapse mortality (19.9% versus 23.0%, P = .71), and the incidence of graft-versus-host disease were not significantly different between the ivBU1 and ivBU4 groups. In patients who received ivBU1, neutrophil recovery was slower (median days: 22 versus 17, P = .001), and the incidence of veno-occlusive disease was lower (2.6% versus 17.4%, P = .04). In conclusion, ivBU1 can be safely administered with clinical outcomes similar to those with ivBU4. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  5. Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial

    Directory of Open Access Journals (Sweden)

    D'Urzo Anthony

    2011-12-01

    Full Text Available Abstract Background NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD. The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1 evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD. Methods Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1 1/forced vital capacity 1 antagonists permitted in patients stabilized on them prior to study entry. The primary outcome measure was trough FEV1 at Week 12. Results A total of 822 patients were randomized to NVA237 (n = 552 or placebo (n = 270. Least squares mean (± standard error trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L, versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p 1 were apparent at the end of Day 1 and sustained through Week 26. FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints. Transition dyspnoea index focal scores and St. George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p Conclusions Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication. Trial registration ClinicalTrials.gov: NCT01005901

  6. Effect of illicit direct to consumer advertising on use of etanercept, mometasone, and tegaserod in Canada: controlled longitudinal study

    Science.gov (United States)

    Majumdar, Sumit R; Soumerai, Stephen B

    2008-01-01

    Objective To assess the impact of direct to consumer advertising of prescription drugs in the United States on Canadian prescribing rates for three heavily marketed drugs—etanercept, mometasone, and tegaserod. Design Controlled quasi-experimental study using interrupted time series analysis. Population Representative sample of 2700 Canadian pharmacies and prescription data from 50 US Medicaid programmes. Main outcome measures Differences in number of filled prescriptions per 10 000 population per month between English speaking and French speaking (control) Canadian provinces before and after the start of direct to consumer advertising in the United States. Results Spending on direct to consumer advertising for study drugs ranged from $194m to $314m (£104m-£169m; €131m-€212m) over the study period. Prescription rates for etanercept and mometasone did not increase in English speaking provinces relative to French speaking controls after the start of direct to consumer advertising. In contrast, tegaserod prescriptions increased 42% (0.56 prescriptions/10 000 residents, 95% confidence interval 0.37 to 0.76) in English speaking provinces immediately after the start of US direct to consumer advertising. Uncontrolled analysis of US Medicaid data showed a larger 56% increase in tegaserod prescriptions. However, this increase did not persist over time in either country, despite continued advertising. Conclusions Exposure to US direct to consumer advertising transiently influenced both Canadian and US prescribing rates for tegaserod, a drug later withdrawn owing to safety concerns. The impact of direct to consumer advertising on drug use seems to be highly variable and probably depends on the characteristics of the advertised drug, the level of exposure to direct to consumer advertising, and the cultural context. PMID:18765444

  7. Exploratory study of once-daily transcranial direct current stimulation (tDCS) as a treatment for auditory hallucinations in schizophrenia.

    Science.gov (United States)

    Fröhlich, F; Burrello, T N; Mellin, J M; Cordle, A L; Lustenberger, C M; Gilmore, J H; Jarskog, L F

    2016-03-01

    Auditory hallucinations are resistant to pharmacotherapy in about 25% of adults with schizophrenia. Treatment with noninvasive brain stimulation would provide a welcomed additional tool for the clinical management of auditory hallucinations. A recent study found a significant reduction in auditory hallucinations in people with schizophrenia after five days of twice-daily transcranial direct current stimulation (tDCS) that simultaneously targeted left dorsolateral prefrontal cortex and left temporo-parietal cortex. We hypothesized that once-daily tDCS with stimulation electrodes over left frontal and temporo-parietal areas reduces auditory hallucinations in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled study that evaluated five days of daily tDCS of the same cortical targets in 26 outpatients with schizophrenia and schizoaffective disorder with auditory hallucinations. We found a significant reduction in auditory hallucinations measured by the Auditory Hallucination Rating Scale (F2,50=12.22, PtDCS for treatment of auditory hallucinations and the pronounced response in the sham-treated group in this study contrasts with the previous finding and demonstrates the need for further optimization and evaluation of noninvasive brain stimulation strategies. In particular, higher cumulative doses and higher treatment frequencies of tDCS together with strategies to reduce placebo responses should be investigated. Additionally, consideration of more targeted stimulation to engage specific deficits in temporal organization of brain activity in patients with auditory hallucinations may be warranted. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat® versus placebo and formoterol twice daily in patients with GOLD 2–4 COPD: results from two replicate 48-week studies

    Directory of Open Access Journals (Sweden)

    Koch A

    2014-07-01

    Full Text Available Andrea Koch,1 Emilio Pizzichini,2 Alan Hamilton,3 Lorna Hart,3 Lawrence Korducki,4 Maria Cristina De Salvo,5 Pierluigi Paggiaro6 1Medical Clinic III for Pneumology, Allergology, Sleep and Respiratory Medicine, University Hospital Bochum-Bergmannsheil, Bochum, Germany; 2NUPAIVA (Asthma Research Center, Universidade Federal de Santa Catarina, Santa Catarina, Brazil; 3Boehringer Ingelheim, Burlington, Ontario, Canada; 4Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 5Centro Médico Dra. De Salvo, Fundación Respirar, Buenos Aires, Argentina; 6Cardio-Thoracic and Vascular Department, University of Pisa, Pisa, Italy Abstract: Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy. Patients received once-daily olodaterol 5 or 10 µg, twice-daily formoterol 12 µg, or placebo. Co-primary end points were forced expiratory volume in 1 second (FEV1 area under the curve from 0–3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George's Respiratory Questionnaire. Overall, 904 (Study 1222.13 and 934 (Study 1222.14 patients received treatment. Olodaterol significantly improved FEV1 area under the curve from 0–3 hours versus placebo in both studies (with olodaterol 5 µg, 0.151 L and 0.129 L; with olodaterol 10 µg, 0.165 L and 0.154 L; for all comparisons P<0.0001 and FEV1 trough responses versus placebo (0.053–0.085 L; P<0.01, as did formoterol. Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo. Post hoc analysis using pattern mixture modeling (accounting for

  9. Dapagliflozin once-daily and exenatide once-weekly dual therapy: A 24-week randomized, placebo-controlled, phase II study examining effects on body weight and prediabetes in obese adults without diabetes.

    Science.gov (United States)

    Lundkvist, Per; Sjöström, C David; Amini, Sam; Pereira, Maria J; Johnsson, Eva; Eriksson, Jan W

    2017-01-01

    To explore the effects of dual therapy with dapagliflozin and exenatide on body weight, body composition, glycaemic variables and systolic blood pressure (SBP) in obese adults without diabetes. In this single-centre, double-blind trial, we randomized 50 obese adults without diabetes (aged 18-70 years; body mass index 30-45 kg/m 2 ) to oral dapagliflozin 10 mg once daily plus subcutaneous long-acting exenatide 2 mg once weekly or placebo. MRI was used to assess change in body composition. Participants were instructed to follow a balanced diet and exercise moderately. Of 25 dapagliflozin/exenatide- and 25 placebo-treated participants, 23 (92.0%) and 20 (80.0%) completed 24 weeks of treatment, respectively. At baseline, the mean participant age was 52 years, 61% were female, the mean body weight was 104.6 kg, and 73.5% of participants had prediabetes (impaired fasting glucose or impaired glucose tolerance). After 24 weeks, for dapagliflozin/exenatide versus placebo: the difference in body weight change was -4.13 kg (95% confidence interval -6.44, -1.81; P prediabetes was less frequent with active treatment (34.8% vs 85.0%, respectively; P prediabetes and SBP over 24 weeks and was well tolerated in obese adults without diabetes. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  10. Lansoprazole 15 mg once daily for 14 days is effective for treatment of frequent heartburn: results of 2 randomized, placebo-controlled, double-blind studies.

    Science.gov (United States)

    Kushner, Pamela R; Snoddy, Andrew M; Gilderman, Larry; Peura, David A

    2009-07-01

    To investigate the efficacy and safety of a 14-day treatment period with lansoprazole 15 mg for frequent heartburn in patients who are likely to select a nonprescription medication before consulting a prescriber. Adults with untreated frequent heartburn > or = 2 days a week over the past month were recruited for 2 identical multicenter, double-blind studies conducted with a 1-week screening and heartburn medication washout, a 1-week placebo run-in, a 2-week placebo-controlled treatment, and a 1-week placebo follow-up. After the washout and placebo run-in, subjects were randomly assigned to receive lansoprazole 15 mg or placebo once daily for 14 days in a double-blind fashion. Antacid tablets were permitted as rescue medication. Endpoints included percentage of 24-hour days without heartburn (primary), percentage of night-times without heartburn, and percentage of subjects without heartburn during day 1 of treatment (secondary endpoints). Data were collected daily via an interactive voice response system. In studies 1 and 2, 282 and 288 subjects, respectively, were randomly assigned to lansoprazole, and 282 in each study received placebo. The mean percentage of days without heartburn was greater among lansoprazole recipients compared with placebo recipients (P heartburn and no heartburn during day 1 of the 14-day treatment. Adverse events were infrequent and were similar for lansoprazole and placebo groups. During the 14-day treatment period in a population with frequent heartburn who were likely to select a medication without consulting a prescriber, lansoprazole 15 mg once daily showed rapid and sustained effectiveness throughout a 24-hour period and was well tolerated.

  11. Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate-Release Tofacitinib and Impact of Food.

    Science.gov (United States)

    Lamba, Manisha; Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C

    2016-11-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended-release (XR) formulation has been designed to provide a once-daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice-daily immediate-release (IR) formulation. We conducted 2 randomized, open-label, phase 1 studies in healthy volunteers. Study A characterized single-dose and steady-state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single-dose and steady-state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high-fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half-life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration-time curve (AUC) and maximum plasma concentration (C max ) after single- and multiple-dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. C max increased by 27% under the fed state. On repeat administration, negligible accumulation (Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. © 2016, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  12. Efficacy and safety of coadministration of once-daily indacaterol and glycopyrronium versus indacaterol alone in COPD patients: the GLOW6 study

    Directory of Open Access Journals (Sweden)

    Vincken W

    2014-02-01

    Full Text Available Walter Vincken,1 Joseph Aumann,2 Hungta Chen,3 Michelle Henley,3 Danny McBryan,4 Pankaj Goyal4 1Respiratory Division, University Hospital, UZ Brussel, Free University of Brussels, Brussels, Belgium; 2Longartsenpraktijk, Prins Bisschopssingel, Hasselt, Belgium; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 4Novartis Pharma AG, Basel, Switzerland Background: Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD whose symptoms are insufficiently controlled by bronchodilator monotherapy. GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND and the long-acting muscarinic antagonist glycopyrronium (GLY versus IND alone in patients with moderate-to-severe COPD. Materials and methods: In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 µg and GLY 50 µg daily (IND + GLY or IND 150 µg daily and placebo (IND + PBO (all delivered via separate Breezhaler® devices. The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1 at week 12. Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min–4h, peak FEV1, inspiratory capacity and trough forced vital capacity (FVC at day 1 and week 12, and transition dyspnea index (TDI focal score, COPD symptoms, and rescue medication use over 12 weeks. Results: A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223; 94% completed the study. On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46–101 mL and 64 mL (95% CI 28–99 mL, respectively (both P<0.001. IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min–4h

  13. The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Bakerly, Nawar Diar; Woodcock, Ashley; New, John P; Gibson, J Martin; Wu, Wei; Leather, David; Vestbo, Jørgen

    2015-09-04

    New treatments need to be evaluated in real-world clinical practice to account for co-morbidities, adherence and polypharmacy. Patients with chronic obstructive pulmonary disease (COPD), ≥ 40 years old, with exacerbation in the previous 3 years are randomised 1:1 to once-daily fluticasone furoate 100 μg/vilanterol 25 μg in a novel dry-powder inhaler versus continuing their existing therapy. The primary endpoint is the mean annual rate of COPD exacerbations; an electronic medical record allows real-time collection and monitoring of endpoint and safety data. The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in COPD. Clinicaltrials.gov identifier NCT01551758.

  14. Effect of prandial treatment timing adjustment, based on continuous glucose monitoring, in patients with type 2 diabetes uncontrolled with once-daily basal insulin: A randomized, phase IV study.

    Science.gov (United States)

    Ilany, Jacob; Bhandari, Hamad; Nabriski, Dan; Toledano, Yoel; Konvalina, Noa; Cohen, Ohad

    2018-05-01

    To evaluate the glycaemic control achieved by prandial once-daily insulin glulisine injection timing adjustment, based on a continuous glucose monitoring sensor, in comparison to once-daily insulin glulisine injection before breakfast in patients with type 2 diabetes who are uncontrolled with once-daily basal insulin glargine. This was a 24-week open-label, randomized, controlled, multicentre trial. At the end of an 8-week period of basal insulin optimization, patients with HbA1c ≥ 7.5% and FPG sensor) or arm B (sensor) to receive 16-week intensified prandial glulisine treatment. Patients in arm A received pre-breakfast glulisine, and patients in arm B received glulisine before the meal with the highest glucose elevation based on sensor data. The primary outcome was mean HbA1c at week 24 and secondary outcomes included rates of hypoglycaemic events and insulin dosage. A total of 121 patients were randomized to arm A (n = 61) or arm B (n = 60). There was no difference in mean HbA1c at week 24 between arms A and B (8.5% ± 1.2% vs 8.4% ± 1.0%; P = .66). The prandial insulin glulisine dosage for arm A and arm B was 9.3 and 10.1 units, respectively (P = .39). The frequency of hypoglycaemic events did not differ between study arms (36.1% vs 51.7%; P = .08). Using a CGM sensor to identify the meal with the highest glucose excursion and adjusting the timing of prandial insulin treatment did not show any advantage in terms of glycaemic control or safety in our patients. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  15. 75 FR 16346 - Ophthalmic and Topical Dosage Form New Animal Drugs; Orbifloxacin, Mometasone Furoate Monohydrate...

    Science.gov (United States)

    2010-04-01

    ... posaconazole for the treatment of otitis externa in dogs. DATES: This rule is effective April 1, 2010. FOR... posaconazole) Otic Suspension for the treatment of otitis externa in dogs associated with susceptible strains... statement is required. Under section 512(c)(2)(F)(ii) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C...

  16. Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction.

    Science.gov (United States)

    Ramiro, Miguel A; Llibre, Josep M

    2014-11-01

    The availability of generic lamivudine in the context of the current economic crisis has raised a new issue in some European countries: breaking up the once-daily fixed-dose antiretroviral combinations (FDAC) of efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or abacavir/lamivudine, in order to administer their components separately, thereby allowing the use of generic lamivudine instead of branded emtricitabine or lamivudine. The legal, ethical, and economic implications of this potential strategy are reviewed, particularly in those patients receiving a once-daily single-tablet regimen. An unfamiliar change in antiretroviral treatment from a successful patient-friendly FDAC into a more complex regimen including separately the components to allow the substitution of one (or some) of them for generic surrogates (in the absence of a generic bioequivalent FDAC) could be discriminatory because it does not guarantee access to equal excellence in healthcare to all citizens. Furthermore, it could violate the principle of non-maleficence by potentially causing harm both at the individual level (hindering adherence and favouring treatment failure and resistance), and at the community level (hampering control of disease transmission and transmission of HIV-1 resistance). Replacing a FDAC with the individual components of that combination should only be permitted when the substituting medication has the same qualitative and quantitative composition of active ingredients, pharmaceutical form, method of administration, dosage and presentation as the medication being replaced, and a randomized study has demonstrated its non-inferiority. Finally, a strict pharma-economic study supporting this change, comparing the effectiveness and the cost of a specific intervention with the best available alternative, should be undertaken before its potential implementation. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiolog

  17. Weather/temperature-sensitive vasomotor rhinitis may be refractory to intranasal corticosteroid treatment.

    Science.gov (United States)

    Jacobs, Robert; Lieberman, Philip; Kent, Edward; Silvey, MaryJane; Locantore, Nicholas; Philpot, Edward E

    2009-01-01

    Vasomotor rhinitis (VMR) is a common but poorly understood disorder of which there are two major subgroups: VMR(w/t), triggered by weather/temperature and VMR(ir), triggered by airborne irritants. No specific biological pathways or specific treatments for VMR(w/t) or VMR(ir) have been identified. However, intranasal corticosteroids (INSs) are effective in treating many forms of nonallergic rhinitis that include these conditions. A recently introduced INS with established efficacy in allergic rhinitis and enhanced affinity, fluticasone furoate, may possess the potency and safety profile required to treat chronic VMR(w/t). Two replicate studies (FFR30006 and FFR30007) were conducted in six countries to evaluate the efficacy and safety of fluticasone furoate nasal spray in subjects with VMR(w/t). After a 7- to 14-day screening period, subjects (n = 699) with symptomatic VMR(w/t) received fluticasone furoate, 110 mug q.d. or placebo for 4 weeks in these two randomized, double-blind, parallel-group studies. Subjects rated their nasal symptoms (congestion, rhinorrhea, and postnasal drip) twice daily on a 4-point categorical scale and evaluated their overall response to treatment at study end. Fluticasone furoate did not significantly improve daily reflective total nasal symptom scores, the primary end point, versus placebo (p = 0.259) and there was no improvement in any other measure of efficacy. The active treatment was well tolerated. Fluticasone furoate was not effective in treating subjects with a newly defined condition, weather-sensitive VMR. These unexpected results suggest that VMR(w/t) is a distinct subgroup of VMR that is refractory to treatment with INSs. Additional study of other treatments for VMR(w/t) (including INSs) is warranted.

  18. A Prospective Open-Label Multicentre Trial on the Use of 1 G, Once Daily Ceftriaxone in Lower Respiratory Tract Infections

    Directory of Open Access Journals (Sweden)

    Donald E Low

    1994-01-01

    in the study. Clinical cure and clinical improvement were achieved in 64.6 and 28.3% of the evaluable patients. respectively. Relapse of infection occurred in two patients (1.8%. and treatment failure was recorded in six cases (5.3%. Twelve patients (8.8% died clue to reasons unrelated to the sludy treatment. Three adverse event (hives, diarrhea and phlebitis at the injection site were possibly related to the study drug. A cross-Canada in vitro susceptibility surveillance study of bacterial pathogens. frequently the cause of pneumonia. found ceftriaxone to have minimal inhibitory concentrations in 90% of isolates that would support such a dosing regimen. with the exception of Enterobacter species. These rcsults support the use of 1 g, once daily ceftriaxone for the empirical treatment of pneumonia in those patients requiring hospitalization.

  19. The short-term cost-effectiveness of once-daily liraglutide versus once-weekly exenatide for the treatment of type 2 diabetes mellitus in the United States.

    Directory of Open Access Journals (Sweden)

    Bruce Wang

    Full Text Available Type 2 diabetes mellitus (T2DM is a chronic metabolic disease with substantial morbidity, mortality, and economic impacts. Glucagon-like peptide-1 (GLP-1 receptor agonists, such as once-daily (QD liraglutide and once-weekly (QW exenatide, are FDA-approved treatment for T2DM. Head-to-head trials and meta-analyses comparing these agents have reported clinically meaningful improvements but small differences in glycemic control between both agents. In this study, we calculate and compare the cost-effectiveness implications of these alternative effectiveness outcomes.We developed a decision model to evaluate the short-term cost-effectiveness of exenatide QW 2 mg versus liraglutide QD 1.8 mg in T2DM patients, with effectiveness measured as reduction in glycated hemoglobin (HbA1c. In the base case, the model tracks change in HbA1c and direct medical expenditure over a 6-month time horizon. We calculated and compared the cost per 1% reduction in HbA1c of models populated with clinical data from a head-to-head randomized, controlled trial (DURATION-6 and a network meta-analysis. Expenditure inputs were derived from wholesale acquisition costs and published sources.In the base case, 6-month expenditure for the liraglutide and exenatide strategies were $3,509 and $2,618, respectively. Using clinical data from DURATION-6 and the network meta-analysis, the liraglutide strategy had an incremental cost per 1% reduction in HbA1c of $4,773 and $27,179, respectively. The most influential model parameters were drug costs, magnitude of HbA1c reduction in patients on treatment for >1 month, and liraglutide gastrointestinal adverse event rate. In probabilistic sensitivity analyses (PSA using DURATION-6 data, the exenatide strategy was optimal at willingness-to-pay levels below $4,800 per 1% reduction in HbA1c. In a PSA using meta-analysis data, the exenatide strategy was dominant.Our modeled results demonstrate that the effectiveness and cost-effectiveness of

  20. The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in asthma.

    Science.gov (United States)

    Woodcock, Ashley; Bakerly, Nawar Diar; New, John P; Gibson, J Martin; Wu, Wei; Vestbo, Jørgen; Leather, David

    2015-12-10

    Novel therapies need to be evaluated in normal clinical practice to allow a true representation of the treatment effectiveness in real-world settings. The Salford Lung Study is a pragmatic randomised controlled trial in adult asthma, evaluating the clinical effectiveness and safety of once-daily fluticasone furoate (100 μg or 200 μg)/vilanterol 25 μg in a novel dry-powder inhaler, versus existing asthma maintenance therapy. The study was initiated before this investigational treatment was licensed and conducted in real-world clinical practice to consider adherence, co-morbidities, polypharmacy, and real-world factors. Asthma Control Test at week 24; safety endpoints include the incidence of serious pneumonias. The study utilises the Salford electronic medical record, which allows near to real-time collection and monitoring of safety data. The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in asthma. Use of patients' linked electronic health records to collect clinical endpoints offers minimal disruption to patients and investigators, and also ensures patient safety. This highly innovative study will complement standard double-blind randomised controlled trials in order to improve our understanding of the risk/benefit profile of fluticasone furoate/vilanterol in patients with asthma in real-world settings. Clinicaltrials.gov, NCT01706198; 04 October 2012.

  1. The economics of 4 grams once daily mesalazine dosing compared with 4 grams twice daily in active ulcerative colitis

    NARCIS (Netherlands)

    Connolly, M.; Kuyvenhoven, J.; Postma, M.; Nielsen, S.

    2013-01-01

    Background: Dosing frequency is an important treatment consideration that has been shown to influence adherence and outcomes when treating ulcerative colitis (UC). In this analysis we evaluate the economic consequences of outcome differences observed in the study comparing mesalazine 4g per day once

  2. Effects of Tadalafil Once-Daily or On-Demand vs Placebo on Return to Baseline Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy - Results from a Randomized Controlled Trial (REACTT)

    DEFF Research Database (Denmark)

    Mulhall, John P; Brock, Gerald; Oelke, Matthias

    2016-01-01

    INTRODUCTION AND AIM: The multicenter, randomized, double-blind, double-dummy, placebo-controlled REACTT trial suggested that treatment with tadalafil once daily (OaD) started early after bilateral nerve-sparing radical prostatectomy (nsRP) for prostate cancer may contribute to erectile function......: REACTT included 422 men blind treatment (DBT) with tadalafil 5 mg OaD (n = 139), tadalafil 20 mg on...

  3. Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial.

    Science.gov (United States)

    Johannsson, Gudmundur; Feldt-Rasmussen, Ulla; Håkonsson, Ida Holme; Biering, Henrik; Rodien, Patrice; Tahara, Shigeyuki; Toogood, Andrew; Rasmussen, Michael Højby

    2018-05-01

    Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin ® . Local tolerability and treatment satisfaction were also assessed. 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939). Male or female patients aged 18-79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan ( n  = 61) or once-daily Norditropin ( n  = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin ( P  = 0.0171). In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin. © 2018 The authors.

  4. Safety update regarding intranasal corticosteroids for the treatment of allergic rhinitis.

    Science.gov (United States)

    Blaiss, Michael S

    2011-01-01

    Intranasal corticosteroids (INSs) are the most efficacious medication for the treatment of allergic rhinitis. In 2006, the Joint Task Force of the American College of Allergy, Asthma, and Immunology, and the American Academy of Allergy, Asthma, and Immunology, published a white paper on the potential over-the-counter switch of INS (Bielory L, Blaiss M, Fineman SM, et al. Concerns about intranasal corticosteroids for over-the-counter use: Position statement of the Joint Task Force for the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 96:514-525, 2006). The concern of the paper was the safety of the use of these agents without oversight by a health care professional. The objective of this paper was to review published literature on the safety of INS since the publication of the task force white paper. Recent studies, which evaluated topical and systemic adverse events associated with ciclesonide (CIC), fluticasone furoate (FF), mometasone furoate (MF), triamcinolone acetonide, fluticasone propionate, budesonide, and beclomethasone dipropionate were summarized. In general, no significant topical or systemic complications were observed in these studies, although none were >1 year in duration. The newer formulations of topical corticosteroids for allergic rhinitis, such as CIC, FF, and MF, which have less systemic bioavailability, may be safer for long-term use. New studies continue to add to the reassurance of the safety of INSs in the treatment of allergic rhinitis but still do not answer the question if these agents are appropriate for long-term use without oversight by a health care professional.

  5. Local control and functional results after twice-daily radiotherapy for Ewing's sarcoma of the extremities

    International Nuclear Information System (INIS)

    Bolek, Timothy W.; Marcus, Robert B.; Mendenhall, Nancy Price; Scarborough, Mark T.; Graham-Pole, John

    1996-01-01

    Purpose: Radiotherapy (RT) has been the predominant local treatment for Ewing's sarcoma of bone at the University of Florida. Twice-daily hyperfractionated RT was initiated in 1982 to improve local control and functional outcome. This retrospective review compares the results of once-daily vs. twice-daily RT in patients with primary Ewing's sarcoma of an extremity, with emphasis on functional outcome. Methods and Materials: Between June 1971 and January 1990, 37 patients were treated at the University of Florida for nonmetastatic Ewing's sarcoma of bone with a primary lesion in an extremity. Three patients underwent amputation. Of 34 patients treated with RT, 31 had RT alone and 3 had a combination of RT and local excision. Before 1982, 14 patients received once-daily RT; since 1982, 17 patients have received twice-daily RT. Doses of once-daily RT varied from 47 to 61 Gy at 1.8-2 Gy per fraction. Doses of twice-daily RT varied, depending on the response of the soft-tissue component of the tumor to chemotherapy, and ranged from 50.4 to 60 Gy at 1.2 Gy per fraction. Some patients in the twice-daily RT group also received total body irradiation 1-3 months after local RT as part of a conditioning regimen before marrow-ablative therapy with stem cell rescue. They received either 8 Gy in two once-daily fractions or 12 Gy in six twice-daily fractions. The six patients who received surgery were excluded from local control analysis. Local control rates were calculated using the Kaplan-Meier (actuarial) method. Fifteen patients had a formal functional evaluation. Results: In the 31 patients treated with RT alone, the actuarial local control rate at 5 years was 81% for patients treated twice daily and 77% for those treated once daily (p = NS). No posttreatment pathologic fractures occurred in patients treated twice daily, whereas five fractures occurred in those treated once daily (p = 0.01). On functional evaluation, less loss in range of motion (15 deg. vs. 28 deg. of loss

  6. Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study.

    Science.gov (United States)

    Leyden, James J; Sniukiene, Vilma; Berk, David R; Kaoukhov, Alexandre

    2018-03-01

    There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris. In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations. Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred. Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other

  7. Cost-effectiveness analysis of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese patients with Type 2 diabetes mellitus inadequately controlled by oral therapies.

    Science.gov (United States)

    Deng, Jing; Gu, Shuyan; Shao, Hui; Dong, Hengjin; Zou, Dajin; Shi, Lizheng

    2015-01-01

    To estimate cost-effectiveness of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese type 2 diabetes patients not well controlled by oral anti-diabetic (OAD) agents. The Cardiff model was populated with data synthesized from three head-to-head randomized clinical trials of up to 30 weeks in China comparing exenatide BID vs insulin glargine as add-on therapies to oral therapies in the Chinese population. The Cardiff model generated outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs, and quality-adjusted life years (QALYs). Cost and QALYs were estimated with a time horizon of 40 years at a discount rate of 3% from a societal perspective. Compared with insulin glargine plus OAD treatments, patients on exenatide BID plus OAD gained 1.88 QALYs, at an incremental cost saving of Chinese Renminbi (RMB) 114,593 (i.e., cost saving of RMB 61078/QALY). The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis. The variables with the most impact on incremental cost-effectiveness ratio included HbA1c level at baseline, health utilities decrement, and BMI at baseline. Compared with insulin glargine QD, exenatide BID as add-on therapy to OAD is a cost-effective treatment in Chinese patients inadequately controlled by OAD treatments.

  8. Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vilsbøll, Tina; Brock, Birgitte; Perrild, Hans

    2008-01-01

    To assess the effect of liraglutide, a once-daily human glucagon-like peptide-1 analogue on pancreatic B-cell function. methods: Patients with Type 2 diabetes (n = 39) were randomized to treatment with 0.65, 1.25 or 1.9 mg/day liraglutide or placebo for 14 weeks. First- and second-phase insulin...... release were measured by means of the insulin-modified frequently sampled intravenous glucose tolerance test. Arginine-stimulated insulin secretion was measured during a hyperglycaemic clamp (20 mmol/l). Glucose effectiveness and insulin sensitivity were estimated by means of the insulin...

  9. Optimization of health-care organization and perceived improvement of patient comfort by switching from intra-venous BU four-times-daily infusions to a once-daily administration scheme in adult hematopoietic stem cell recipients.

    Science.gov (United States)

    Xhaard, A; Rzepecki, P; Valcarcel, D; Santarone, S; Fürst, S; Serrano, D; De Angelis, G; Krüger, W; Scheid, C

    2014-04-01

    Previous studies have shown an equivalent pharmacokinetic profile between four-times-daily (4QD) and once-daily (QD) administration of intra-venous (IV) BU, without increased toxicity. We assess the impact of a switch in IV BU from a 4QD to a QD schedule, in terms of health-care organization, staff working conditions, quality of care dispensed and perceived patient comfort. Clinicians, nurses and pharmacists from nine allogeneic transplantation units in five European countries were interviewed face to face. Overall perception of QD versus 4QD BU was very positive. Both administration schemes were evaluated to be equally efficaciousZ. QD BU was perceived to be safer and more convenient. Clinicians and nurses perceived that patient comfort was improved, due to fewer complications associated with repeated infusions, and avoiding night infusions associated with stress, anxiety and decreased quality of sleep. Switching from 4QD to QD BU had a significant impact on health-care organization, with a better integration in the overall management and usual timelines in the pharmacies and transplantation units. Time spent to prepare and administer BU was significantly reduced, leading to potential financial savings that merit further assessment and would be of particular interest in the current economic climate.

  10. Review of once-monthly oral ibandronate and the use thereof

    African Journals Online (AJOL)

    The MOBILE study was a prospective, randomised, phase lll, non- inferiority study that compared the efficacy and safety of three once-monthly oral ibandronate doses (50+50 mg monthly, given on 2 consecutive days; 100 mg monthly; 150 mg monthly) with. 2.5 mg daily ibandronate, which has previously been shown.

  11. Control of hypertension with single daily doses of sotalol hydrochloride.

    Science.gov (United States)

    Gabriel, R

    A study was carried out in 12 previously untreated hypertensive patients to assess the efficacy of sotalol given in a once-daily dosage regimen. After an initial dosage titration period (mean 3 weeks) during which diastolic pressure was stabilized at less than 100 mmHg, all patients were satisfactorily maintained on a constant once-daily dose of sotalol for 3 months. Eight of the 12 patients required 320 mg or less daily (mean dose 190 mg). Whilst blood pressure remained controlled for at least 26 hours after daily doses the pulse rate, counted at the same time, showed escape from beta-blockade. Side-effects (vivid dreams) were reported in only 1 patient.

  12. Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study.

    Science.gov (United States)

    Arnold, Lesley M; Arsenault, Pierre; Huffman, Cynthia; Patrick, Jeffrey L; Messig, Michael; Chew, Marci L; Sanin, Luis; Scavone, Joseph M; Pauer, Lynne; Clair, Andrew G

    2014-10-01

    Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.

  13. Teriflunomide: a once-daily oral medication for the treatment of relapsing forms of multiple sclerosis.

    Science.gov (United States)

    Miller, Aaron E

    2015-10-01

    The purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes. In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. After recent updates to the prescribing information (October 2014), key findings from these and 2 other Phase III clinical trials, TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis) and TOPIC (Oral Teriflunomide for Patients with a First Clinical Episode Suggestive of Multiple Sclerosis), and practical considerations for physicians are summarized. Teriflunomide, 14 mg and 7 mg, significantly reduced mean number of unique active lesions on magnetic resonance imaging (MRI; P treatment was also associated with significant efficacy on MRI measures of disease activity in TEMSO; both doses significantly reduced total lesion volume and number of gadolinium-enhancing T1 lesions. TOPIC evaluated patients with a first clinical event consistent with acute demyelination and brain MRI lesions characteristic of multiple sclerosis. More patients were free of relapse in the teriflunomide 14-mg and 7-mg groups than in the placebo group (P treatment are recommended to assess potential safety issues. Women of childbearing potential must use effective contraception and, in the event of pregnancy, undergo an accelerated elimination procedure to reduce plasma concentrations of teriflunomide. Clinical evidence suggests that teriflunomide is an effective therapeutic choice for patients with RMS, both as an initial treatment and as an alternative for patients who may have experienced intolerance or inadequate response to a previous or current disease-modifying therapy. Copyright © 2015 The Authors

  14. Dry matter intake, body condition score, and grazing behavior of nonlactating, pregnant dairy cows fed kale or grass once versus twice daily during winter.

    Science.gov (United States)

    Rugoho, I; Edwards, G R

    2018-01-01

    The objective of this study was to examine the effect of wintering pregnant, nonlactating dairy cows outdoors on either kale or grass, fed in 1 [11 kg dry matter (DM) of kale or grass + 3 kg DM of baled barley straw offered in the morning] or 2 allocations (5.5 kg DM of kale or grass grazed + 1.5 kg DM of barley straw offered morning and afternoon) per day. The body condition score (BCS) gain over the 47-d winter feeding period was higher for grass-fed (0.5 BCS units) than kale-fed cows (0.3 BCS units), but was unaffected by feeding frequency. Forage DM utilization was higher for kale-fed (97%) than grass-fed cows (76%), leading to higher estimated dry matter intake (DMI) in kale-fed (10.7 kg of DM/cow per day) than grass-fed cows (7.7 kg of DM/cow per day). Forage DM utilization and estimated DMI were not affected by feeding frequency. Prehension bite rate was greater for grass-fed (37.3 bites/min) than kale-fed cows (7.6 bites/min), but more mastication bites were required for kale-fed cows. Cumulative DMI after 2, 3, and 6 h was greater in cows allocated forage once than twice a day and for kale than grass after 3 and 6 h. Mean eating time was greater for cows offered forage once (477 min) than twice (414 min) per day. In conclusion, increasing feeding frequency from once to twice per day decreased the intake rate within the first 6 h after allocation, but did not affect total daily DMI, DM utilization or BCS gain. Thus, moving cows more frequently would not have any significant advantage. It may increase labor requirements, thereby creating a more challenging wintering management than feeding once per day. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. Randomised clinical trial: alginate (Gaviscon Advance) vs. placebo as add-on therapy in reflux patients with inadequate response to a once daily proton pump inhibitor.

    Science.gov (United States)

    Reimer, C; Lødrup, A B; Smith, G; Wilkinson, J; Bytzer, P

    2016-04-01

    Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor (PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach content and thus offer a supplemental mechanism of action to acid suppression. To assess the efficacy of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. This was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using the Heartburn Reflux Dyspepsia Questionnaire (HRDQ). Based on symptom score during run-in, eligible patients were randomised to Gaviscon Advance 10 mL four times a day or placebo in addition to a once daily PPI. The primary endpoint was change in HRDQ score post-treatment compared to baseline. One hundred and thirty-six patients were randomised. Change in HRDQ reflux score was significantly greater for Gaviscon Advance (mean: -5.0, s.d.: 4.7) than for placebo (mean: -3.5, s.d.: 5.5) with an LS mean difference of 1.6 [95% CI -3.1 to -0.1], P = 0.03. A decrease in the mean (s.d.) number of nights with symptoms was observed from 3.6 (2.8) to 3.0 (3.0) in the placebo group and from 3.9 (2.8) to 2.2 (2.7) for the Gaviscon Advance group. This reduction was significantly greater in the Gaviscon Advance group than in the placebo group [LS mean difference = -0.9, 95% CI (-1.6 to -0.2), P < 0.01]. In patients with residual reflux symptoms despite PPI treatment, adding an alginate offers additional decrease in the burden of reflux symptoms (EudraCT/IND Number: 2011-005486-21). © 2016 John Wiley & Sons Ltd.

  16. Once upon an algorithm how stories explain computing

    CERN Document Server

    Erwig, Martin

    2017-01-01

    How Hansel and Gretel, Sherlock Holmes, the movie Groundhog Day, Harry Potter, and other familiar stories illustrate the concepts of computing. Picture a computer scientist, staring at a screen and clicking away frantically on a keyboard, hacking into a system, or perhaps developing an app. Now delete that picture. In Once Upon an Algorithm, Martin Erwig explains computation as something that takes place beyond electronic computers, and computer science as the study of systematic problem solving. Erwig points out that many daily activities involve problem solving. Getting up in the morning, for example: You get up, take a shower, get dressed, eat breakfast. This simple daily routine solves a recurring problem through a series of well-defined steps. In computer science, such a routine is called an algorithm. Erwig illustrates a series of concepts in computing with examples from daily life and familiar stories. Hansel and Gretel, for example, execute an algorithm to get home from the forest. The movie Groundho...

  17. Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties.

    Science.gov (United States)

    Rygg, Alex; Hindle, Michael; Longest, P Worth

    2016-04-01

    The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.

  18. One-by-one or all-at-once? Self-reporting policies and dishonesty

    NARCIS (Netherlands)

    Rilke, R.M.; Schurr, A.; Barkan, R.; Shalvi, S.

    2016-01-01

    Organizational monitoring relies frequently on self-reports (e.g., work hours, progress reports, travel expenses). A "one-by-one" policy requires employees to submit a series of reports (e.g., daily or itemized reports). An "all-at-once" policy requires an overall report (e.g., an annual or an

  19. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial.

    OpenAIRE

    Rascol, O.; Brooks, D.J.; Melamed, E.; Oertel, W.; Poewe, W.; Stocchi, F.; Tolosa, E.; LARGO study group

    2005-01-01

    Lancet. 2005 Mar 12-18;365(9463):947-54. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Rascol O, Brooks DJ, Melamed E, Oertel W, Poewe W, Stocchi F, Tolosa E; LARGO study group. Clinical Investigation Centre, Department of Clinical Pharmacology, University Hospital, Toulouse, France. ...

  20. Fifteen-year results of a randomized prospective trial of hyperfractionated chest wall irradiation versus once-daily chest wall irradiation after chemotherapy and mastectomy for patients with locally advanced noninflammatory breast cancer

    International Nuclear Information System (INIS)

    Buchholz, Thomas A.; Strom, Eric A.; Oswald, Mary Jane; Perkins, George H.; Oh, Julia; Domain, Delora; Yu, Tse-Kuan; Woodward, Wendy A.; Tereffe, Welela; Singletary, S. Eva; Thomas, Eva; Buzdar, Aman U.; Hortobagyi, Gabriel N.; McNeese, Marsha D.

    2006-01-01

    Purpose: To analyze the results of a Phase III clinical trial that investigated whether a hyperfractionated radiotherapy (RT) schedule could reduce the risk of locoregional recurrence in patients with locally advanced breast cancer treated with chemotherapy and mastectomy. Methods and Materials: Between 1985 and 1989, 200 patients with clinical Stage III noninflammatory breast cancer were enrolled in a prospective study investigating neoadjuvant and adjuvant chemotherapy. Of the 179 patients treated with mastectomy after neoadjuvant chemotherapy, 108 participated in a randomized component of the trial that compared a dose-escalated, hyperfractionated (twice-daily, b.i.d.) chest wall RT schedule (72 Gy in 1.2-Gy b.i.d. fractions) with a once-daily (q.d.) schedule (60 Gy in 2-Gy q.d. fractions). In both arms of the study, the supraclavicular fossa and axillary apex were treated once daily to 50 Gy. The median follow-up period was 15 years. Results: The 15-year actuarial locoregional recurrence rate was 7% for the q.d. arm and 12% for the b.i.d. arm (p = 0.36). The rates of severe acute toxicity were similar (4% for q.d. vs. 5% for b.i.d.), but moist desquamation developed in 42% of patients in the b.i.d. arm compared with 28% of the patients in the q.d. arm (p = 0.16). The 15-year actuarial rate of severe late RT complications did not differ between the two arms (6% for q.d. vs. 11% for b.i.d., p = 0.54). Conclusion: Although the sample size of this study was small, we found no evidence that this hyperfractionation schedule of postmastectomy RT offered a clinical advantage. Therefore, we have concluded that it should not be further studied in this cohort of patients

  1. 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.

  2. The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer's disease taking cholinesterase inhibitors.

    Science.gov (United States)

    Grossberg, George T; Manes, Facundo; Allegri, Ricardo F; Gutiérrez-Robledo, Luis Miguel; Gloger, Sergio; Xie, Lei; Jia, X Daniel; Pejović, Vojislav; Miller, Michael L; Perhach, James L; Graham, Stephen M

    2013-06-01

    Immediate-release memantine (10 mg, twice daily) is approved in the USA for moderate-to-severe Alzheimer's disease (AD). This study evaluated the efficacy, safety, and tolerability of a higher-dose, once-daily, extended-release formulation in patients with moderate-to-severe AD concurrently taking cholinesterase inhibitors. In this 24-week, double-blind, multinational study (NCT00322153), outpatients with AD (Mini-Mental State Examination scores of 3-14) were randomized to receive once-daily, 28-mg, extended-release memantine or placebo. Co-primary efficacy parameters were the baseline-to-endpoint score change on the Severe Impairment Battery (SIB) and the endpoint score on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus). The secondary efficacy parameter was the baseline-to-endpoint score change on the 19-item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19); additional parameters included the baseline-to-endpoint score changes on the Neuropsychiatric Inventory (NPI) and verbal fluency test. Data were analyzed using a two-way analysis of covariance model, except for CIBIC-Plus (Cochran-Mantel-Haenszel test). Safety and tolerability were assessed through adverse events and physical and laboratory examinations. A total of 677 patients were randomized to receive extended-release memantine (n = 342) or placebo (n = 335); completion rates were 79.8 and 81.2 %, respectively. At endpoint (week 24, last observation carried forward), memantine-treated patients significantly outperformed placebo-treated patients on the SIB (least squares mean difference [95 % CI] 2.6 [1.0, 4.2]; p = 0.001), CIBIC-Plus (p = 0.008), NPI (p = 0.005), and verbal fluency test (p = 0.004); the effect did not achieve significance on ADCS-ADL19 (p = 0.177). Adverse events with a frequency of ≥5.0 % that were more prevalent in the memantine group were headache (5.6 vs. 5.1 %) and diarrhea (5.0 vs. 3.9

  3. Whole-abdomen radiotherapy for non-Hodgkin's lymphoma using twice-daily fractionation

    International Nuclear Information System (INIS)

    Liauw, Stanley L.; Yeh, Alexander M.; Morris, Christopher G.; Olivier, Kenneth R.; Mendenhall, Nancy Price

    2006-01-01

    Purpose: To report the tolerability and efficacy of twice-daily whole-abdomen irradiation (WAI) for non-Hodgkin's lymphoma (NHL). Methods and Materials: Of 123 patients treated for NHL with WAI, 37% received previous chemotherapy, 28% received WAI as part of comprehensive lymphatic irradiation (CLI), and 32% received WAI for palliation. The median dose to the whole abdomen was 25.0 Gy, followed by a median tumor boost of 9.8 Gy in 58 patients. Fractionation was 1.0 Gy once daily (54%) or 0.8 Gy twice daily (46%). Blood counts were measured weekly. Results: At a median follow-up of 4.3 years, local control was 72% and overall survival was 55% at 5 years. Median time of WAI was 42 days for once-daily treatment and 32 days for twice-daily treatment. Patients receiving twice-daily WAI did not have a significantly higher rate of acute side effects (e.g., nausea, diarrhea, platelet or red blood cell toxicity). Overall, acute thrombocytopenia was the most frequent side effect of treatment; 24 of 96 patients (25%) with available hematologic data had Grade 3+ toxicity. There was no acute Grade 3 gastrointestinal toxicity and no late small bowel obstruction. Multiple regression indicated that patients with four or less involved sites and disease size ≤6 cm had improved local control and overall survival. Conclusions: Twice-daily WAI using 0.8 Gy/fraction does not appear to have any greater toxicity compared with once-daily treatment using 1 Gy/fraction. Small doses per fraction (0.8-1 Gy/fx) are effective, tolerated well in the acute setting, and associated with a low rate of late toxicity

  4. Once-daily transdermal rivastigmine in the treatment of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Andreas Wentrup

    2008-11-01

    Full Text Available Andreas Wentrup, Wolfgang H Oertel, Richard DodelDepartment of Neurology, Philipps-University Marburg, GermanyAbstract: During the past decade, transdermal delivery systems (TDS have become increasingly important for treating neurologic and psychiatric disorders. The rivastigmine patch was the first patch to be approved to treat Alzheimer’s disease (AD. The 9.5 mg/24 h patch has equal efficacy to the capsules and reduces gastrointestinal adverse events, such as nausea and vomiting, by two-thirds. This treatment is well tolerated by patients because drug delivery is even and continuous, reducing fluctuation in drug plasma level, and attenuating the development of centrally mediated cholinergic side effects. Furthermore, once-a-day application of the patch enables an easy treatment schedule, ease of handling, infrequent skin irritations, and a patient- and caregiver-friendly mode of administration. Improved compliance with a subsequent drug administration may contribute to better clinical efficacy, reduce caregiver burden, result in a slower rate of institutionalization, and lead to a decrease in healthcare and medical costs. Because of these advantages, the rivastigmine patch has enabled great progress in the treatment of AD, and represents an excellent alternative to the orally administered cholinesterase inhibitors.Keywords: Alzheimer’s disease, rivastigmine, patch, dementia

  5. Pharmacodynamic analysis and clinical trial of amoxicillin sprinkle administered once daily for 7 days compared to penicillin V potassium administered four times daily for 10 days in the treatment of tonsillopharyngitis due to Streptococcus pyogenes in children.

    Science.gov (United States)

    Pichichero, M E; Casey, J R; Block, S L; Guttendorf, R; Flanner, H; Markowitz, D; Clausen, S

    2008-07-01

    An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (T >MIC; based on the MIC(90) of 0.06 microg/ml for Streptococcus pyogenes reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formulation of amoxicillin (amoxicillin sprinkle). The daily T >MIC achieved with the QD amoxicillin sprinkle formulation was comparable to that achieved with a four-times-daily (QID) penicillin VK suspension. An investigator-blinded, randomized, parallel-group, multicenter study involving 579 children 6 months to 12 years old with acute streptococcal tonsillopharyngitis was then undertaken. Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7 days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle and 68.0% (132/194) for penicillin VK (95% confidence interval, -12.0% to 6.6%). Thus, neither antibiotic regimen met the minimum criterion of > or =85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to S. pyogenes. The results of subgroup analyses across demographic characteristics and current infection characteristics and by age/weight categories were consistent with the primary-efficacy result. The clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1% (216/251) and 91.9% (204/222), respectively (95% confidence interval, -11.6% to -0.4%). The results of a post hoc PD analysis suggested that a requirement for 60% daily T >MIC(90) more accurately predicted the observed high failure rates for bacteriologic eradication with the amoxicillin sprinkle and penicillin VK suspension studied. Based on the association between

  6. Pilot study of once-daily simplification therapy with abacavir/lamivudine/zidovudine and efavirenz for treatment of HIV-1 infection.

    Science.gov (United States)

    Ruane, Peter; Lang, Joseph; DeJesus, Edwin; Berger, Daniel S; Dretler, Robin; Rodriguez, Allan; Ward, Douglas J; Lim, Michael L; Liao, Qiming; Reddy, Sunila; Clair, Marty St; Vila, Tania; Shaefer, Mark S

    2006-01-01

    The purpose of this pilot study was to explore the efficacy and safety of the abacavir/lamivudine/zidovudine fixed-dose combination tablet administered as two tablets once daily (qd) versus one tablet twice daily (bid) in combination with efavirenz (EFV). This was a prospective, randomized, open-label, multicenter study with a 24-week treatment period in 7 outpatient HIV clinics in the United States. Patients currently receiving an initial regimen of abacavir/lamivudine/zidovudine bid plus EFV qd for at least 6 months with HIV-1 RNA or = 200 cells/mm3 were eligible. Thirty-six patients enrolled, and 35 (97%) completed the study. Participants were randomized to switch to 2 tablets of abacavir/lamivudine/zidovudine qd plus EFV qd (QD arm) or continue current treatment (BID arm) for 24 weeks. Efficacy, safety, and adherence were evaluated. Median baseline CD4+ cell count was 521 cells/mm3. At week 24, HIV-1 RNA or = 0.29 to +0.18, p = 1.000). At week 24, median CD4+ cell count change from baseline was +26 cells/mm3 for the QD arm and -39 cells/mm3 for BID arm. One patient randomized to the QD arm met virologic failure criteria (confirmed HIV-1 RNA >120 copies/mL) at week 20 and viral genotype showed M184V. After failure, this patient revealed he never took EFV throughout the entire study after randomization, effectively receiving only abacavir/lamivudine/zidovudine qd alone. Median adherence was slightly higher in the QD arm, although both arms had broad variability and overlapping interquartile ranges. Adverse events were infrequent and occurred with similar frequency between arms; treatment-related adverse events were abdominal pain, flatulence, nausea, headache, and abnormal dreams (1 patient [3%] for each adverse event). No patients withdrew due to adverse events, and no abacavir hypersensitivity reactions were reported. In this pilot study of patients suppressed on abacavir/lamivudine/zidovudine bid plus EFV, 94% of participants switching to abacavir

  7. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial.

    Science.gov (United States)

    Rascol, O; Brooks, D J; Melamed, E; Oertel, W; Poewe, W; Stocchi, F; Tolosa, E

    Rasagiline mesylate is a novel drug for Parkinson's disease with selective, irreversible monoamine oxidase B (MAO-B) inhibitor activity, and is effective as monotherapy in early disease. This study investigated rasagiline efficacy and safety in levodopa-treated patients with Parkinson's disease and motor fluctuations. In an 18-week, double-blind, multicentre (74 hospitals and academic centres in Israel, Argentina, and Europe) trial, 687 outpatients were randomly assigned to oral rasagiline (231 individuals; 1 mg once daily), entacapone (227; 200 mg with every levodopa dose), or placebo (229). Primary outcome was change in total daily off-time (intention-to-treat population). Other measures included the clinical global improvement (CGI) score and unified Parkinson's disease rating scale (UPDRS) scores. Analysis was by intention to treat. 88 (13%) patients who were assigned treatment did not complete the study (23 rasagiline, 30 entacapone, 35 placebo), mainly because of withdrawal of consent (n=34) and adverse events (n=34). Both rasagiline and entacapone reduced mean daily off-time (-1.18 h rasagiline and -1.2 h entacapone vs placebo -0.4 h; p=0.0001, prasagiline and -0.72 entacapone vs -0.37 placebo; prasagiline reduces mean daily off-time and improves symptoms of Parkinson's disease in levodopa-treated patients with motor fluctuations, an effect similar to that of entacapone.

  8. Switch from a ZDV/3TC-based regimen to a completely once daily (QD regimen of emtricitabine/tenofovir DF fixed dose combination plus a third QD agent (SONETT

    Directory of Open Access Journals (Sweden)

    Arasteh K

    2009-05-01

    Full Text Available Abstract Objectives To assess the efficacy and safety of a treatment switch from a twice-daily (BID regimen containing zidovudine (ZDV and lamivudine (3TC plus a third agent to a once daily (QD regimen containing the fixed-dose combination of tenofovir DF/emtricitabine (TDF/FTC, Truvada® plus a divergent third QD agent in HIV-1 infected patients. Methods Prospective, 48-week, non-randomised, single-group, open-label, study. Fifty-one patients on stable ZDV/3TC-containing HAART, with HIV-1 RNA 50 cells/μl, were switched to TDF/FTC plus a third agent. Plasma HIV-1 RNA, CD4+ and CD8+ T-cell counts were assessed at baseline and weeks 4, 12, 24, 36 and 48 post-switch. Results During the 48-week study, 10 patients discontinued prematurely, including three due to adverse events (AEs. At week 48, plasma HIV-1 RNA was p Conclusions Results from this study support switching from a ZDV/3TC-containing HAART regimen to a completely QD regimen of TDF/FTC plus a third agent. Virologic and immunologic control are maintained, with apparent benefits in haemoglobin.

  9. Drug Repurposing from an Academic Perspective.

    Science.gov (United States)

    Oprea, Tudor I; Bauman, Julie E; Bologa, Cristian G; Buranda, Tione; Chigaev, Alexandre; Edwards, Bruce S; Jarvik, Jonathan W; Gresham, Hattie D; Haynes, Mark K; Hjelle, Brian; Hromas, Robert; Hudson, Laurie; Mackenzie, Debra A; Muller, Carolyn Y; Reed, John C; Simons, Peter C; Smagley, Yelena; Strouse, Juan; Surviladze, Zurab; Thompson, Todd; Ursu, Oleg; Waller, Anna; Wandinger-Ness, Angela; Winter, Stuart S; Wu, Yang; Young, Susan M; Larson, Richard S; Willman, Cheryl; Sklar, Larry A

    2011-01-01

    Academia and small business research units are poised to play an increasing role in drug discovery, with drug repurposing as one of the major areas of activity. Here we summarize project status for a number of drugs or classes of drugs: raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate, astemizole, R-naproxen, ketorolac, tolfenamic acid, phenothiazines, methylergonovine maleate and beta-adrenergic receptor drugs, respectively. Based on this multi-year, multi-project experience we discuss strengths and weaknesses of academic-based drug repurposing research. Translational, target and disease foci are strategic advantages fostered by close proximity and frequent interactions between basic and clinical scientists, which often result in discovering new modes of action for approved drugs. On the other hand, lack of integration with pharmaceutical sciences and toxicology, lack of appropriate intellectual coverage and issues related to dosing and safety may lead to significant drawbacks. The development of a more streamlined regulatory process world-wide, and the development of pre-competitive knowledge transfer systems such as a global healthcare database focused on regulatory and scientific information for drugs world-wide, are among the ideas proposed to improve the process of academic drug discovery and repurposing, and to overcome the "valley of death" by bridging basic to clinical sciences.

  10. Single-use autoinjector for once-weekly intramuscular injection of IFNβ-1a.

    Science.gov (United States)

    Limmroth, Volker; Gerbershagen, Kathrin

    2014-12-01

    IFNβ products and glatiramer acetate are established treatment first-line options in long-term disease-modifying therapy of multiple sclerosis (MS). These self-injectable medications are used once weekly to once daily. Injection-related issues are common patient-cited reasons for nonadherence. Autoinjectors have been shown to support long-term adherence to injectable medications. The ability to self-inject in MS patients has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patient independence. The recently introduced easy-to-use prefilled once-weekly pen is a safe and effective device for intramuscular (IM) IFNβ-1a application and provides a convenient method for self-injection. We reviewed the available published evidence on the characteristics of this device. The once-weekly pen facilitates self-injection and was preferred over prefilled syringes by patients in a prospective open-label, multicenter Phase IIIb trial in MS patients who had been using IM IFNβ-1a in prefilled syringes. The simple and safe handling, shielded short needle, single-use disposable design and virtually painless injection by the device may contribute to adherence, quality of life and independence in patients using IM IFNβ-1a.

  11. Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

    Science.gov (United States)

    Hale, Martin E; Nalamachu, Srinivas R; Khan, Arif; Kutch, Michael

    2013-01-01

    Purpose To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER) during dose conversion and titration. Patients and methods A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio), and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs) and serious AEs. Results Mean (standard deviation) final daily dose of OROS hydromorphone ER was 37.5 (17.8) mg. Mean (standard error of the mean [SEM]) numeric rating scale scores decreased from 6.6 (0.1) at screening to 4.3 (0.1) at the final titration visit (mean [SEM] change, −2.3 [0.1], representing a 34.8% reduction). Mean (SEM) change in Patient Global Assessment was −0.6 (0.1), and mean change (SEM) in the Roland–Morris Disability Questionnaire was −2.8 (0.3). Patients achieving a stable dose showed greater improvement than patients who discontinued during titration for each of these measures (P < 0.001). Almost 80% of patients achieving a stable dose (213/268) had a ≥30% reduction in pain. Commonly reported AEs were constipation (15.4%), nausea (11.9%), somnolence (8.7%), headache (7.8%), and vomiting (6.5%); 13.0% discontinued from the study due to AEs. Conclusion The majority of opioid-tolerant patients with chronic low back pain were successfully converted to effective doses of

  12. Pharmacodynamic Analysis and Clinical Trial of Amoxicillin Sprinkle Administered Once Daily for 7 Days Compared to Penicillin V Potassium Administered Four Times Daily for 10 Days in the Treatment of Tonsillopharyngitis Due to Streptococcus pyogenes in Children▿

    Science.gov (United States)

    Pichichero, M. E.; Casey, J. R.; Block, S. L.; Guttendorf, R.; Flanner, H.; Markowitz, D.; Clausen, S.

    2008-01-01

    An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (T >MIC; based on the MIC90 of 0.06 μg/ml for Streptococcus pyogenes reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formulation of amoxicillin (amoxicillin sprinkle). The daily T >MIC achieved with the QD amoxicillin sprinkle formulation was comparable to that achieved with a four-times-daily (QID) penicillin VK suspension. An investigator-blinded, randomized, parallel-group, multicenter study involving 579 children 6 months to 12 years old with acute streptococcal tonsillopharyngitis was then undertaken. Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7 days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle and 68.0% (132/194) for penicillin VK (95% confidence interval, −12.0% to 6.6%). Thus, neither antibiotic regimen met the minimum criterion of ≥85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to S. pyogenes. The results of subgroup analyses across demographic characteristics and current infection characteristics and by age/weight categories were consistent with the primary-efficacy result. The clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1% (216/251) and 91.9% (204/222), respectively (95% confidence interval, −11.6% to −0.4%). The results of a post hoc PD analysis suggested that a requirement for 60% daily T >MIC90 more accurately predicted the observed high failure rates for bacteriologic eradication with the amoxicillin sprinkle and penicillin VK suspension studied. Based on the association between longer

  13. Cost-effectiveness of exenatide twice daily vs insulin glargine as add-on therapy to oral antidiabetic agents in patients with type 2 diabetes in China.

    Science.gov (United States)

    Gu, Shuyan; Wang, Xiaoyong; Qiao, Qing; Gao, Weiguo; Wang, Jian; Dong, Hengjin

    2017-12-01

    To estimate the long-term cost-effectiveness of exenatide twice daily vs insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM). The Cardiff Diabetes Model was used to simulate disease progression and estimate the long-term effects of exenatide twice daily vs insulin glargine once daily. Patient profiles and treatment effects required for the model were obtained from literature reviews (English and Chinese databases) and from a meta-analysis of 8 randomized controlled trials comparing exenatide twice daily with insulin glargine once daily add-on to OADs for T2DM in China. Medical expenditure data were collected from 639 patients with T2DM (aged ≥18 years) with and without complications incurred between January 1, 2014 and December 31, 2015 from claims databases in Shandong, China. Costs (2014 Chinese Yuan [¥]) and benefits were estimated, from the payers' perspective, over 40 years at a discount rate of 3%. A series of sensitivity analyses were performed. Patients on exenatide twice daily + OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic events and lower total costs compared with those on insulin glargine once daily + OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost saving of ¥117 706 gained was associated with exenatide twice daily vs insulin glargine once daily. (i.e. cost saving of ¥60 764/QALY) per patient. In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice daily is a cost-effective add-on therapy alternative to insulin glargine once daily, and may address the problem of an excess of medical needs resulting from weight gain and hypoglycaemia in T2DM treatment. © 2017 John Wiley & Sons Ltd.

  14. Review of Efficacy and Safety of Duloxetine 40 to 60 mg Once Daily in Patients with Diabetic Peripheral Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Vladimir Skljarevski

    2012-01-01

    Full Text Available We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studies and 1 open-label, uncontrolled, 34-week maintenance-of-effect (MOE study that examine duloxetine 40 and 60 mg once daily (QD in patients with diabetic peripheral neuropathic pain (DPNP. In all placebo-controlled studies, duloxetine showed significantly (P≤.01 greater reduction in pain severity (weekly mean of 24-hour average pain severity ratings, primary outcome measure compared with placebo. In all placebo-controlled studies, duloxetine showed significantly (P≤.05 greater improvement on brief pain inventory-Interference ratings. Patient global impression of improvement ratings were superior to placebo (P≤.01 for duloxetine patients in all placebo-controlled studies. Response rates (based on 30% pain reduction ranged from 57% to 68% for duloxetine and from 35% to 47% for placebo and were statistically significantly different (P≤.01 between treatment groups in 3 out of 4 studies. The open-label study showed maintenance of analgesic effect of duloxetine in DPNP. In the duloxetine groups, 4.3% to 14.9% of patients discontinued because of adverse events (placebo groups: 2.6% to 7.4%. Most commonly reported treatment-emergent adverse events were nausea, somnolence, and headache. Duloxetine 40 and 60 mg QD was efficacious and well tolerated in the management of DPNP.

  15. Cost effectiveness of once-daily oral chelation therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassaemia patients: US healthcare system perspective.

    Science.gov (United States)

    Delea, Thomas E; Sofrygin, Oleg; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

    2007-01-01

    Deferasirox is a recently approved once-daily oral iron chelator that has been shown to reduce liver iron concentrations and serum ferritin levels to a similar extent as infusional deferoxamine. To determine the cost effectiveness of deferasirox versus deferoxamine in patients with beta-thalassaemia major from a US healthcare system perspective. A Markov model was used to estimate the total additional lifetime costs and QALYs gained with deferasirox versus deferoxamine in patients with beta-thalassaemia major and chronic iron overload from blood transfusions. Patients were assumed to be 3 years of age at initiation of chelation therapy and to receive prescribed dosages of deferasirox and deferoxamine that have been shown to be similarly effective in such patients. Compliance with chelation therapy and probabilities of iron overload-related cardiac disease and death by degree of compliance were estimated using data from published studies. Costs ($US, year 2006 values) of deferoxamine administration and iron overload-related cardiac disease were based on analyses of health insurance claims of transfusion-dependent thalassaemia patients. Utilities were based on a study of patient preferences for oral versus infusional chelation therapy, as well as published literature. Probabilistic and deterministic sensitivity analyses were employed to examine the robustness of the results to key assumptions. Deferasirox resulted in a gain of 4.5 QALYs per patient at an additional expected lifetime cost of $US126,018 per patient; the cost per QALY gained was $US28,255. The cost effectiveness of deferasirox versus deferoxamine was sensitive to the estimated costs of deferoxamine administration and the quality-of-life benefit associated with oral versus infusional therapy. Cost effectiveness was also relatively sensitive to the equivalent daily dose of deferasirox, and the unit costs of deferasirox and deferoxamine, and was more favourable in younger patients. Results of this analysis

  16. A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation.

    Science.gov (United States)

    Alai, Milind; Lin, Wen Jen

    2013-01-01

    The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration.

  17. 76 FR 6794 - 30-Day Submission Period for Requests for ONC-Approved Accreditor (ONC-AA) Status

    Science.gov (United States)

    2011-02-08

    ... Accreditor (ONC-AA) Status AGENCY: Office of the National Coordinator for Health Information Technology... submission of requests for ONC-Approved Accreditor (ONC-AA) status. Authority: 42 U.S.C. 300jj-11. DATES: The... for ONC-AA status may be submitted. The 30-day period for submission of requests for ONC-AA status...

  18. Comparative efficacy of tadalafil once daily in men with erectile dysfunction who demonstrated previous partial responses to as-needed sildenafil, tadalafil, or vardenafil.

    Science.gov (United States)

    Kim, Edward; Seftel, Allen; Goldfischer, Evan; Baygani, Simin; Burns, Patrick

    2015-02-01

    Phosphodiesterase type-5 inhibitors (PDE5Is) are first-line therapies for erectile dysfunction (ED). Sildenafil (SIL) and vardenafil (VAR) are approved for as-needed (PRN) dosing; tadalafil (TAD) is approved for both PRN and once-a-day (OaD) dosing for ED. Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy. This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy. In this randomized, double-blind, placebo-controlled trial, men with a ≥3 month ED history received SIL 100 mg, TAD 20 mg, or VAR 20 mg during a 4 week open-label lead-in period. Those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain scores TAD 2.5 mg up-titrated to 5 mg, TAD 5 mg, or placebo (PBO) OaD for 12 weeks. MAIN OUTCOME MEASURES obtained from patients treated with TAD-OaD were compared to PBO-treated patients. Additionally, results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy. NCT01130532. International Index of Erectile Function (IIEF) domain scores; Sexual Encounter Profile (SEP) questions 2-5. Endpoint data was obtained from 590 men (391 TAD; 199 PBO). RESULTS for all IIEF and SEP measures were significantly better for TAD-OaD (p TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated. Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED. Key limitations include the lack of a PRN PDE5I study group during the double-blind period, and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period.

  19. Once-daily milking during a feed deficit decreases milk production but improves energy status in early lactating grazing dairy cows.

    Science.gov (United States)

    Kay, J K; Phyn, C V C; Rius, A G; Morgan, S R; Grala, T M; Roche, J R

    2013-10-01

    The objective of this study was to investigate the effect of milking frequency (MF) at 2 feeding levels (FL) on milk production, body condition score, and metabolic indicators of energy status in grazing dairy cows during early lactation. Multiparous Holstein-Friesian and Holstein-Friesian × Jersey cows (n=120) grazed pasture and were milked twice daily (2×) from calving until 34 ± 6 d in milk (mean ± standard deviation). Cows were then allocated to 1 of 4 treatments in a 2 × 2 factorial arrangement. Treatments consisted of 2 FL: adequately fed [AF; 14.3 kg dry matter intake (DMI)/cow per d] or underfed (UF; 8.3 kg of DMI/cow per d) and 2 MF: 2× or once daily (1×). Treatments were imposed for 3 wk. After the treatment period, all cows were offered a generous pasture allowance (grazing residuals >1,600 kg of dry matter/ha) and milked 2×. During the 3-wk treatment period, we observed an interaction between FL and MF for energy-corrected milk (ECM), such that the decrease due to 1× milking was greater in AF than in UF cows (20 and 14% decrease, respectively). No interactions were found posttreatment. Cows previously UF produced 7% less ECM than AF cows during wk 4 to 12; however, no subsequent effect was observed of the previous underfeeding. Cows previously milked 1× produced 5% less ECM during wk 4 to 12, and differences remained during wk 13 to 23. During the 3-wk treatment period, UF cows lost 0.2 body condition score units (1-10 scale) and this was not affected by 1× milking. During the treatment period, UF cows had lower plasma glucose, insulin, and insulin-like growth factor I, and greater nonesterified fatty acids and β-hydroxybutyrate concentrations than AF cows. Cows milked 1× had greater plasma glucose, insulin, and insulin-like growth factor I, and lower nonesterified fatty acids and β-hydroxybutyrate concentrations compared with cows milked 2×. In conclusion, energy status was improved by 1× milking; however, when UF cows were milked 1

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

    Science.gov (United States)

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

    2015-01-01

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

  1. Scheduling reinforcement about once a day.

    Science.gov (United States)

    Eckerman, D A

    1999-04-01

    A pigeon earned its daily food by pecking a key according to reinforcement schedules that produced food about once per day. Fixed-interval (FI), Fixed-time (FT), and various complex schedules were arranged to demonstrate the degree to which a scalloped pattern of responding remained. Pausing continued until about an hour before the reinforcer could be earned for FIs of 12, 24, and 48 h. Pausing was not as long for FIs of 18, 19, and 23 h. Pausing of about 24 h was seen for FI 36 h. FT 24 h produced continued responding but at a diminished frequency. The pattern of responding was strongly controlled by the schedule of reinforcement and seemed relatively independent of the cycle of human activity in the surrounding laboratory. Effects of added ratio contingencies and of signaling the availability of reinforcement in FT were also examined. Signaled FTs of 5 min-3 h produced more responding during the signal (autoshaping) than did FTs of 19 or 24 h.

  2. Comparison of insulin intensification strategies with insulin lispro low mixture twice daily versus basal insulin glargine and prandial insulin lispro once daily in East Asian and Caucasian patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Jeong, In-Kyung; Chung, Choon Hee; Zhou, Zhiguang; Han, Jeong Hee; Duan, Ran; Edralin, Diana M; Rodriguez, Angel

    2017-04-01

    This analysis evaluated efficacy and safety of insulin lispro low mixture (LM25) twice daily (breakfast and dinner) versus basal insulin glargine (bedtime) plus prandial insulin lispro (IGL) once daily before the largest meal in East Asian (EA) and Caucasian patients with type 2 diabetes mellitus who failed to reach glycemic targets on basal insulin glargine with metformin and/or pioglitazone. Included patients had an HbA1c ≥7.5% and ≤10.5% and fasting plasma glucose ≤6.7 mmol/L. Primary outcome was HbA1c change at 24 weeks. Baseline mean HbA1c was numerically similar between groups in EA (n = 79) and Caucasian (n = 278) patients. Mean (± SD) HbA1c decreased significantly from baseline to 24 weeks for LM25 and IGL in both subpopulations (EA: -1.32 ± 0.96% and -0.89 ± 0.96%; Caucasian: -1.24 ± 0.98% and -1.04 ± 0.97; all P 1). The respective proportions reaching HbA1c ≤7.0% at Week 24 in the LM25 and IGL groups were 33.3% and 22.9% (EA) and 37.2% and 34.1% (Caucasian). Mean (± SD) rates of hypoglycemia per 30 days in the LM25 and IGL groups were 0.74 ± 1.16 and 1.22 ± 1.36 (EA) and 1.38 ± 2.04 and 1.65 ± 2.43 (Caucasian). Mean (± SD) weight gain changes in the LM25 and IGL groups were 0.62 ± 2.78 and 0.51 ± 2.63 kg (EA) and 1.77 ± 2.91 and 0.67 ± 3.09 kg (Caucasian). Both strategies improved glycemic control in a small group of EA and Caucasian patients not adequately controlled on insulin glargine plus metformin and/or pioglitazone. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  3. Concentrations of dapivirine in the rhesus macaque and rabbit following once daily intravaginal administration of a gel formulation of [14C]dapivirine for 7 days.

    Science.gov (United States)

    Nuttall, Jeremy P; Thake, Daryl C; Lewis, Mark G; Ferkany, John W; Romano, Joseph W; Mitchnick, Mark A

    2008-03-01

    Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivirine ( approximately 0.1 mg/ml [15 microCi/ml]) to rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels associated with vaginal and cervical tissue samples 1 h after the final dose were high (quantities of microg/g of tissue) and remained detectable at 24 h (mean, >or=2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity levels were low in the plasma and very low or unquantifiable in the draining lymph nodes of the macaques. Microautoradiography identified drug-related material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits and macaques. Although DRM was primarily associated with the outermost layer of shedding cells in rabbits, two animals showed some evidence of small quantities in the mucosal epithelium of the cervix. In macaques, DRM was seen within the keratinized layer of the vaginal epithelium and and was found to extend into the superficial cellular layers, and in at least one animal it appeared to be present in the deepest (germinal) layer of the epithelium and in submucosal tissues. The persistence of biologically significant concentrations of dapivirine in vaginal and cervical tissues for >24 h supports the development of dapivirine as a microbicide for once daily application.

  4. Concentrations of Dapivirine in the Rhesus Macaque and Rabbit following Once Daily Intravaginal Administration of a Gel Formulation of [14C]Dapivirine for 7 Days▿

    Science.gov (United States)

    Nuttall, Jeremy P.; Thake, Daryl C.; Lewis, Mark G.; Ferkany, John W.; Romano, Joseph W.; Mitchnick, Mark A.

    2008-01-01

    Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivirine (∼0.1 mg/ml [15 μCi/ml]) to rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels associated with vaginal and cervical tissue samples 1 h after the final dose were high (quantities of μg/g of tissue) and remained detectable at 24 h (mean, ≥2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity levels were low in the plasma and very low or unquantifiable in the draining lymph nodes of the macaques. Microautoradiography identified drug-related material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits and macaques. Although DRM was primarily associated with the outermost layer of shedding cells in rabbits, two animals showed some evidence of small quantities in the mucosal epithelium of the cervix. In macaques, DRM was seen within the keratinized layer of the vaginal epithelium and and was found to extend into the superficial cellular layers, and in at least one animal it appeared to be present in the deepest (germinal) layer of the epithelium and in submucosal tissues. The persistence of biologically significant concentrations of dapivirine in vaginal and cervical tissues for >24 h supports the development of dapivirine as a microbicide for once daily application. PMID:18086845

  5. Inhalation by design: novel ultra-long-acting β(2)-adrenoreceptor agonists for inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease that utilize a sulfonamide agonist headgroup.

    Science.gov (United States)

    Glossop, Paul A; Lane, Charlotte A L; Price, David A; Bunnage, Mark E; Lewthwaite, Russell A; James, Kim; Brown, Alan D; Yeadon, Michael; Perros-Huguet, Christelle; Trevethick, Michael A; Clarke, Nicholas P; Webster, Robert; Jones, Rhys M; Burrows, Jane L; Feeder, Neil; Taylor, Stefan C J; Spence, Fiona J

    2010-09-23

    A novel series of potent and selective sulfonamide derived β(2)-adrenoreceptor agonists are described that exhibit potential as inhaled ultra-long-acting bronchodilators for the treatment of asthma and chronic obstructive pulmonary disease. Analogues from this series mediate very long-lasting smooth muscle relaxation in guinea pig tracheal strips. The sulfonamide agonist headgroup confers high levels of intrinsic crystallinity that could relate to the acidic sulfonamide motif supporting a zwitterionic form in the solid state. Optimization of pharmacokinetic properties was achieved through targeted introduction of a phenolic moiety to support rapid phase II clearance, thereby minimizing systemic exposure following inhalation and reducing systemically mediated adverse events. Compound 38 (PF-610355) is identified as a clinical candidate from this series, with in vivo duration of action studies confirming its potential for once-daily use in humans. Compound 38 is currently in advanced phase II clinical studies.

  6. Bacterial contamination of stethoscope chest pieces and the effect of daily cleaning.

    Science.gov (United States)

    Fujita, H; Hansen, B; Hanel, R

    2013-01-01

    Stethoscopes are a potential source of nosocomial infection for hospitalized humans, a phenomenon not previously studied in companion animals. To determine if daily cleaning of stethoscope chest pieces reduces bacterial contamination between cleanings. Client-owned dogs and cats. Prospective observational study. In phase 1, bacterial cultures were obtained from the chest pieces of 10 participant stethoscopes once weekly for 3 weeks. In phase 2, stethoscopes were cleaned daily and 2 culture samples were obtained once weekly, immediately before and after cleaning with 70% isopropyl alcohol, for 3 weeks. Daily cleaning eliminated bacteria immediately after each cleaning (P = .004), but did not reduce the rate of positive cultures obtained before cleaning in phase 2. Cultures were positive for 20/30 (67%) samples during phase 1 and 18/30 (60%) obtained before daily cleaning during phase 2. Recovered organisms included normal skin flora, agents of opportunistic infections, and potential pathogens. The only genus that was repeatedly recovered from the same stethoscope for 2 or more consecutive weeks was Bacillus sp. Daily cleaning was highly effective at removing bacteria, but provided no reduction in precleaning contamination. Cleaning stethoscopes after use on dogs or cats infected with pathogenic bacteria and before use on immunocompromised animals should be considered. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  7. Once vs. twice daily thoracic irradiation in limited stage small cell lung cancer

    International Nuclear Information System (INIS)

    Kim, Jun Sang; Kim, Jae Sung; Kim, Ju Ock; Kim, Sun Young; Cho, Moon June

    1998-01-01

    A retrospective study was conducted comparing single dally fraction (SDF) thoracic radiotherapy (TRT) with twice daily (BID) TRT to determine the potential benefit of BID TRT in limited-stage small cell lung cancer (SCLC). Endpoints of the study were response, survival, pattern of failure, and acute toxicity. Between November 1989 to December 1996, 78 patients with histologically proven limited-stage SCLC were treated at the Department of Therapeutic Radiology, Chungnam National University Hospital. Of these, 9 were irradiated for palliative intent, and 1 had recurrent disease. Remaining 68 patients were enrolled in this study. There were 26 patients with a median age of 58 years, and 22 (85%) ECOG performance score of less than 1 in SDF TRT. There were 42 patients with a median age of 57 years, and 36 (86%) ECOG performance score of less than 1 in BID TRT. By radiation fractionation regimen, there were 26 in SDF TRT and 42 in BID TRT. SDF TRT consisted of 180 cGy, 5 days a week. BID TRT consisted of 150 cGY BID, 5 days a week in 13 of 42 and 120 cGy BID, in 29 of 42. And the twice daily fractions were separated by at least 4 hours. Total radiotherapy doses were between 5040 and 6940 cGy (median, 5040 cGy) in SDF TRT and was between 4320 and 5100 cGy (median, 4560 cGy) in BID TRT. Prophylactic cranial irradiation (PCI) was recommended for patients who achieved a CR. The recommended PCI dose was 2500 cGy/10 fractions. Chemotherapy consisted of CAV (cytoxan 1000 mg/m 2 , adriamycin 40 mg/m 2 , vincristine 1 mg/m 2 ) alternating with VPP (cisplatin 60 mg/m 2 , etoposide 100 mg/m 2 ) every 3 weeks in 25 (96%) of SDF TRT and in 40 (95%) of BID TRT. Median cycle of chemotherapy was six in both group. Timing for chemotherapy was sequential in 23 of SDF TRT and in 3 BID TRT, and concurrent in 3 of SDF TRT and in 39 of BID TRT. Follow-up ranged from 2 of 99 months (median, 14 months) in both groups. Of the 26 SDF TRT, 9 (35%) achieved a complete response (CR) and 14 (54

  8. Pharmacokinetics of and short-term virologic response to low-dose 400-milligram once-daily raltegravir maintenance therapy.

    NARCIS (Netherlands)

    Ananworanich, J.; Gorowara, M.; Avihingsanon, A.; Kerr, S.J.; Heesch, N. van; Khongpetch, C.; Uanithirat, A.; Hill, A.; Ruxrungtham, K.; Burger, D.M.

    2012-01-01

    Because studies showed similar viral suppression with lower raltegravir doses and because Asians usually have high antiretroviral concentrations, we explored low-dose raltegravir therapy in Thais. Nineteen adults on raltegravir at 400 mg twice daily (BID) with HIV RNA loads of <50 copies/ml were

  9. Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

    Directory of Open Access Journals (Sweden)

    Hale ME

    2013-05-01

    Full Text Available Martin E Hale,1 Srinivas R Nalamachu,2 Arif Khan,3 Michael Kutch4,* 1Gold Coast Research, LLC, Weston, FL, USA; 2International Clinical Research Institute, Overland Park, KS, USA; 3MedNorthwest Clinical Research Center, Bellevue, WA, USA; Duke University Medical Center, Durham, NC, USA; 4Applied Clinical Intelligence, LLC, Bala Cynwyd, PA, USA *Affiliation at the time this work was completed. Michael Kutch is currently affiliated with Cytel Inc, Chesterbrook, PA, USA Purpose: To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER during dose conversion and titration. Patients and methods: A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio, and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs and serious AEs. Results: Mean (standard deviation final daily dose of OROS hydromorphone ER was 37.5 (17.8 mg. Mean (standard error of the mean [SEM] numeric rating scale scores decreased from 6.6 (0.1 at screening to 4.3 (0.1 at the final titration visit (mean [SEM] change, -2.3 [0.1], representing a 34.8% reduction. Mean (SEM change in Patient Global Assessment was -0.6 (0.1, and mean change (SEM in the Roland–Morris Disability Questionnaire was -2.8 (0.3. Patients achieving a stable dose showed greater improvement

  10. Onychomycosis of Toenails and Post-hoc Analyses with Efinaconazole 10% Solution Once-daily Treatment: Impact of Disease Severity and Other Concomitant Associated Factors on Selection of Therapy and Therapeutic Outcomes.

    Science.gov (United States)

    Del Rosso, James Q

    2016-02-01

    Topical treatment for toenail onychomycosis has been fraught with a long-standing reputation of poor efficaey, primarily due to physical properties of the nail unit that impede drug penetration. Newer topical agents have been formulated as Solution, which appear to provide better therapeutic response in properly selected patients. It is important to recognize the impact the effects that mitigating and concomitant factors can have on efficaey. These factors include disease severity, gender, presence of tinea pedis, and diabetes. This article reviews results achieved in Phase 3 pivotal studies with topical efinaconazole 10% Solution applied once daily for 48 weeks with a focus on how the aforementioned factors influenced therapeutic outcomes. It is important for clinicians treating patients for onychomycosis to evaluate severity, treat concomitant tinea pedis, address control of diabetes if present by encouraging involvement of the patient's primary care physician, and consider longer treatment courses when clinically relevant.

  11. Effect of once-daily insulin detemir on oral antidiabetic drug (OAD) use in patients with type 2 diabetes.

    Science.gov (United States)

    Vora, J; Caputo, S; Damci, T; Orozco-Beltran, D; Pan, C; Svendsen, A L; Sølje, K S; Khunti, K

    2014-04-01

    There are acknowledged benefits to continuing metformin when initiating insulin, but there appears to be growing concern over the role of sulphonylureas and thiazolidinediones when used in combination with insulin. This analysis investigates the effects of continuing or discontinuing oral antidiabetic drugs (OADs) following the initiation of once-daily insulin detemir. SOLVE is a 24-week, multinational observational study of insulin detemir initiation in patients with type 2 diabetes mellitus treated with one or more OADs. In the total cohort (n = 17 374), there were significant improvements in HbA1c (-1·3%, 95% CI -1·34; -1·27%) and weight (-0·6 kg, 95% CI -0·65; -0·47 kg), with an increase in the incidence rate of minor hypoglycaemia (+0·256 events ppy, P use either prior to (n = 17 086) or during insulin initiation (n = 16 346). HbA1c reductions were significantly greater in patients continuing treatment with metformin (-1·3% vs. -1·1%, P < 0·01), thiazolidinediones (-1·3% vs. -1·0%, P < 0·01) and DPP-IV inhibitors (-1·3% vs. -0·9%, P < 0·001). Final insulin doses were significantly greater in patients discontinuing treatment with sulphonylureas (0·29 vs. 0·26 IU/kg, P < 0·001), glinides (0·28 vs. 0·26 IU/kg, P < 0·01), thiazolidinediones (0·31 vs. 0·26 IU/kg, P < 0·001) and DPP-IV inhibitors (0·35 vs. 0·29 IU/kg, P < 0·001) compared with patients continuing these respective agents. All patient subgroups had a mean weight loss irrespective of OAD continuation, apart from those continuing thiazolidinediones (+0·2 kg). The largest improvements in weight were seen following the withdrawal of sulphonylureas and thiazolidinediones (-1·1 and -1·1 kg, respectively). Discontinuation (or switching) of OADs at the time of insulin initiation appears to be governed principally by concerns about hypoglycaemia and weight. HbA1c improvements were smaller in patients discontinuing OADs at the time of insulin

  12. Once-daily long-acting beta-agonists for chronic obstructive pulmonary disease: an indirect comparison of olodaterol and indacaterol

    Directory of Open Access Journals (Sweden)

    Roskell NS

    2014-07-01

    Full Text Available Neil S Roskell,1 Antonio Anzueto,2 Alan Hamilton,3 Bernd Disse,4 Karin Becker5 1Statistics, Bresmed Health Solutions Ltd, Sheffield, UK; 2School of Medicine, University of Texas Health Science Center, San Antonio, TX, USA; 3Medical Department, Boehringer Ingelheim (Canada Ltd, Burlington, ON, Canada; 4Medical Department, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany; 5Global Health Economics and Outcomes Research, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany Purpose: In the absence of head-to-head clinical trials comparing the once-daily, long-acting beta2-agonists olodaterol and indacaterol for the treatment of chronic obstructive pulmonary disease (COPD, an indirect treatment comparison by systematic review and synthesis of the available clinical evidence was conducted. Methods: A systematic literature review of randomized, controlled clinical trials in patients with COPD was performed to evaluate the efficacy and safety of olodaterol and indacaterol. Network meta-analysis and adjusted indirect comparison methods were employed to evaluate treatment efficacy, using outcomes based on trough forced expiratory volume in 1 second (FEV1, Transition Dyspnea Index, St George’s Respiratory Questionnaire total score and response, rescue medication use, and proportion of patients with exacerbations. Results: Eighteen trials were identified for meta-analysis (eight, olodaterol; ten, indacaterol. Olodaterol trials included patients of all severities, whilst indacaterol trials excluded patients with very severe COPD. Concomitant maintenance bronchodilator use was allowed in most olodaterol trials, but not in indacaterol trials. When similarly designed trials/data were analyzed for change from baseline in trough FEV1 (liters, the following mean differences (95% confidence interval were observed: trials excluding concomitant bronchodilator: indacaterol 75 mcg versus olodaterol 5 mcg, –0.005 (–0.077 to 0.067, and indacaterol 150 mcg

  13. Once Daily Valacyclovir for Reducing Viral Shedding in Subjects Newly Diagnosed with Genital Herpes

    Directory of Open Access Journals (Sweden)

    Mark G. Martens

    2009-01-01

    Results. 52 subjects had at least one PCR measurement in both treatment periods and comprised the primary efficacy population. Valacyclovir significantly reduced HSV-2 shedding during all days compared to placebo (mean 2.9% versus 13.5% of all days (P<.01, a 78% reduction. Valacyclovir significantly reduced subclinical HSV-2 shedding during all days compared to placebo (mean 2.4% versus 11.0% of all days (P<.01, a 78% reduction. However, 79% of subjects had no GH recurrences while receiving valacyclovir compared to 52% of subjects receiving placebo (P<.01. Conclusion. In this study, the frequency of total and subclinical HSV-2 shedding was greater than reported in earlier studies involving subjects with a history of symptomatic genital recurrences. Our study is the first to demonstrate a significant reduction in viral shedding with valacyclovir 1 g daily compared to placebo in a population of subjects newly diagnosed with HSV-2 infection.

  14. Once-daily fosamprenavir with ritonavir in the treatment of HIV infection in therapy-naïve patients

    OpenAIRE

    Gisslen, Magnus; Flamholc,Leo; Gisslen,Magnus

    2008-01-01

    Leo Flamholc1, Magnus Gisslén21Department of Infectious Diseases, Malmö University Hospital, Malmö, Sweden; 2Sahlgrenska University Hospital/Östra, Gothenburg, SwedenAbstract: Treatment options for HIV patients have dramatically improved since the introduction of efficacious antiretroviral combination therapy more than a decade ago. Treatment regimens have been simplified with fewer pills and fewer daily dosages. Fosamprenavir is a protease inhibitor with...

  15. Daily Administration of Short-Acting Liothyronine Is Associated with Significant Triiodothyronine Excursions and Fails to Alter Thyroid-Responsive Parameters.

    Science.gov (United States)

    Jonklaas, Jacqueline; Burman, Kenneth D

    2016-06-01

    Although most studies of levothyroxine-liothyronine combination therapy employ once-daily hormone administration, the kinetics of once-daily liothyronine have been studied infrequently. The aim of this study was to document both the peak and trough serum triiodothyronine (T3) levels that occur with once-daily liothyronine administration, along with changes in thyroid-responsive parameters. Participants with hypothyroidism were studied prospectively at an academic institution. Patients were switched from levothyroxine monotherapy to liothyronine monotherapy with 15 μg liothyronine for two weeks, and then continued liothyronine at doses of 30-45 μg for a further four weeks in an open-label, single-arm study. Weekly trough levels of T3 were documented. In addition, hourly T3 concentrations immediately following liothyronine tablet administration were documented for eight hours during the sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4) concentrations were documented. Biochemical markers, markers of energy metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were also assessed. Mean serum TSH levels increased from 1.56 ± 0.81 mIU/L at baseline to 5.90 ± 5.74 mIU/L at two weeks and 3.84 ± 3.66 mIU/L at six weeks. Trough T3 levels decreased from 99.5 ± 22.9 to 91.9 ± 40.2 at two weeks and recovered to 96.1 ± 32.2 at six weeks. The peak T3 concentration after dosing of liothyronine during week 6 was 292.8 ± 152.3 ng/dL. fT4 levels fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4. The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p = 0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at weeks 4-5 of liothyronine therapy (p = 0.04-0.005). Preference for liothyronine therapy increased from 6% to 39% over the study period. Once-daily dosing of liothyronine at doses of 30-45 μg did not return serum

  16. Preclinical evaluation of the imipridone family, analogs of clinical stage anti-cancer small molecule ONC201, reveals potent anti-cancer effects of ONC212.

    Science.gov (United States)

    Wagner, Jessica; Kline, Christina Leah; Ralff, Marie D; Lev, Avital; Lulla, Amriti; Zhou, Lanlan; Olson, Gary L; Nallaganchu, Bhaskara Rao; Benes, Cyril H; Allen, Joshua E; Prabhu, Varun V; Stogniew, Martin; Oster, Wolfgang; El-Deiry, Wafik S

    2017-10-02

    Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene activation. ONC201 is under investigation in multiple clinical trials to treat patients with cancer. Given the unique imipridone core chemical structure of ONC201, we synthesized a series of analogs to identify additional compounds with distinct therapeutic properties. Several imipridones with a broad range of in vitro potencies were identified in an exploration of chemical derivatives. Based on in vitro potency in human cancer cell lines and lack of toxicity to normal human fibroblasts, imipridones ONC206 and ONC212 were prioritized for further study. Both analogs inhibited colony formation, and induced apoptosis and downstream signaling that involves the integrated stress response and Akt/ERK, similar to ONC201. Compared to ONC201, ONC206 demonstrated improved inhibition of cell migration while ONC212 exhibited rapid kinetics of activity. ONC212 was further tested in >1000 human cancer cell lines in vitro and evaluated for safety and anti-tumor efficacy in vivo. ONC212 exhibited broad-spectrum efficacy at nanomolar concentrations across solid tumors and hematological malignancies. Skin cancer emerged as a tumor type with improved efficacy relative to ONC201. Orally administered ONC212 displayed potent anti-tumor effects in vivo, a broad therapeutic window and a favorable PK profile. ONC212 was efficacious in vivo in BRAF V600E melanoma models that are less sensitive to ONC201. Based on these findings, ONC212 warrants further development as a drug candidate. It is clear that therapeutic utility extends beyond ONC201 to include additional imipridones.

  17. ONC201: Stressing tumors to death.

    Science.gov (United States)

    Endo Greer, Yoshimi; Lipkowitz, Stanley

    2016-02-16

    The small molecule ONC201 was identified in a screen for compounds that would induce expression of the gene encoding tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in tumors and thus cause an autocrine- or paracrine-induced death in tumor cells. Two Research Articles in this issue of Science Signaling by Ishizawa et al. and Kline et al. describe how ONC201 can also trigger cytotoxicity by inducing a stress response. The mechanisms of the stress response induced differ between hematological malignancies and solid tumors, highlighting the complexity of ONC201-induced toxicity and raising intriguing issues of tissue-specific pathways activated by the drug. Copyright © 2016, American Association for the Advancement of Science.

  18. Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes.

    Science.gov (United States)

    Wysham, Carol H; Rosenstock, Julio; Vetter, Marion L; Dong, Fang; Öhman, Peter; Iqbal, Nayyar

    2018-01-01

    To simplify administration of aqueous exenatide once weekly, which requires reconstitution, the exenatide microspheres have been reformulated in a ready-to-use autoinjector with a Miglyol diluent (exenatide QWS-AI). This study compared the efficacy and safety of exenatide QWS-AI with the first-in-class glucagon-like peptide-1 receptor agonist exenatide twice daily (BID). This randomized, open-label, controlled study in patients with type 2 diabetes using diet and exercise or taking stable oral glucose-lowering medication randomized patients 3:2 to either exenatide QWS-AI (2 mg) or exenatide BID (10 μg) for 28 weeks. The primary outcome was the 28-week change in glycated haemoglobin (HbA1c). A subset of patients completed a standardized meal test for postprandial and pharmacokinetic assessments. A total of 375 patients (mean HbA1c, 8.5% [69 mmol/mol]; body mass index, 33.2 kg/m 2 ; diabetes duration, 8.5 years) received either exenatide QWS-AI (n = 229) or exenatide BID (n = 146); HbA1c was reduced by -1.4% and -1.0%, respectively (least-squares mean difference, -0.37%; P = .0072). More patients achieved HbA1c <7.0% with exenatide QWS-AI (49.3%) than with exenatide BID (43.2%; P = .225). Body weight was reduced in both groups (P = .37 for difference). Gastrointestinal adverse events (AEs) were reported in 22.7% (exenatide QWS-AI) and 35.6% (exenatide BID) of patients; fewer patients in the exenatide QWS-AI group withdrew because of AEs than in the exenatide BID group. Minor hypoglycaemia occurred most often with concomitant sulfonylurea use. Exenatide QWS-AI was associated with a greater reduction in HbA1c, similar weight loss and a favorable gastrointestinal AE profile compared with exenatide BID. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  19. Algebraic Factoring algorithm to recognise read-once functions.

    NARCIS (Netherlands)

    Naidu, S.R.

    2003-01-01

    A fast polynomial-time algorithm was recently proposed to determine whether a logic function expressed as a unate DNF (disjunctive normal form) can be expressed as a read-once formula where each variable appears no more than once. The paper uses a combinatorial characterisation of read-once formulas

  20. Randomised study to assess the efficacy and safety of once-daily etravirine-based regimen as a switching strategy in HIV-infected patients receiving a protease inhibitor-containing regimen. Etraswitch study.

    Directory of Open Access Journals (Sweden)

    Patricia Echeverría

    Full Text Available Etravirine (ETR was approved for patients with virological failure and antiretroviral resistance mutations. It has also shown antiviral efficacy in antiretroviral-naïve patients. However, data on the switching from protease inhibitors (PI to ETR are lacking.HIV-1-infected patients with suppressed viral load (VL during a PI-containing regimen (>12 months and no previous virological failure were randomized to switch from the PI to ETR (400 mg/day, dissolved in water (ETR group, n = 22 or to continue with the same regimen (control group, n = 21. Percentage of patients with VL ≤ 50 copies/mL were assessed at week 48, as well as changes in CD4 T-cell counts and metabolic profile.We included 43 patients [72.9% male, 46.3 (42.2; 50.6 years]. Two patients receiving ETR (grade-1 diarrhea and voluntary discontinuation and another in the control group (simplification discontinued therapy early. No patients presented virological failure (two consecutive VL>50 copies/mL; treatment was successful in 95.2% of the control group and 90.9% of the ETR group (intention-to-treat analysis, missing = failure (p = 0.58. CD4+ T-cell counts did not significantly vary [+49 cells/µL in the ETR group (p = 0.25 and -4 cells/µL in the control group (p = 0.71]. The ETR group showed significant reductions in cholesterol (p<0.001, triglycerides (p = <0.001, and glycemia (p = 0.03 and higher satisfaction (0-10 scale (p = 0.04. Trough plasma concentrations of ETR were similar to observed in studies using ETR twice daily.Switch from a PI-based regimen to a once-daily combination based on ETR maintained undetectable VL during 48 weeks in virologically suppressed HIV-infected patients while lipid profile and patient satisfaction improved significantly.ClinicalTrials.gov NCT01034917.

  1. An introduction to the Micrel Micropump MP Daily portable syringe driver.

    Science.gov (United States)

    Groves, Karen E

    2003-11-01

    In this article the author describes the Micrel Micropump MP Daily (MP Daily) portable syringe driver. This follows the author's experience of a 4-month pilot of the device by an inpatient palliative care unit. Portable syringe drivers are commonly used to deliver continuous subcutaneous infusions in palliative care situations. Those in current use are not without problems and serious adverse events have occasionally been reported, mainly resulting from confusion between models. The MP Daily syringe driver addresses some of these issues while remaining small, lightweight and inexpensive, with a long battery life and fitting into the pocket of a shirt of pyjama jacket. Improvements over current models include an on/off button, the absence of facilities to set a zero rate or change the rate once the syringe driver is running, and the absence of a boost button. In addition, there are improved alarms, a message display system and a configuration menu. Although confusion remains a problem, and the ideal has not yet been reached, the MP Daily goes some considerable way towards reducing risks and opportunities for human error.

  2. Pegylated Long-Acting Human Growth Hormone Possesses a Promising Once-Weekly Treatment Profile, and Multiple Dosing Is Well Tolerated in Adult Patients with Growth Hormone Deficiency

    DEFF Research Database (Denmark)

    Søndergaard, Esben; Klose, Marianne; Hansen, Mette

    2011-01-01

    Background: Recombinant human GH (rhGH) replacement therapy in children and adults currently requires daily sc injections for several years or lifelong, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed for once-weekly administration. Objectives...

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

    Directory of Open Access Journals (Sweden)

    Ross Lisa L

    2008-03-01

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

  4. Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug monitoring performance.

    LENUS (Irish Health Repository)

    Egan, Sean

    2012-08-07

    BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires good practice in dose selection and monitoring of serum levels. Suboptimal therapy occurs with breakdown in the process of drug dosing, serum blood sampling, laboratory processing and level interpretation. Unintentional underdosing may result. This improvement effort aimed to optimise this process in an academic teaching hospital using Six Sigma process improvement methodology. METHODS: A multidisciplinary project team was formed. Process measures considered critical to quality were defined, and baseline practice was examined through process mapping and audit. Root cause analysis informed improvement measures. These included a new dosing and monitoring schedule, and standardised assay sampling and drug administration timing which maximised local capabilities. Three iterations of the improvement cycle were conducted over a 24-month period. RESULTS: The attainment of serum level sampling in the required time window improved by 85% (p≤0.0001). A 66% improvement in accuracy of dosing was observed (p≤0.0001). Unnecessary dose omission while awaiting level results and inadvertent disruption to therapy due to dosing and monitoring process breakdown were eliminated. Average daily dose administered increased from 3.39 mg\\/kg to 4.78 mg\\/kg\\/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin usage process performance. Local process related factors may adversely affect adherence to practice guidelines for gentamicin, a drug which is complex to use. It is vital to adapt dosing guidance and monitoring requirements so that they are capable of being implemented in the clinical environment as a matter of routine. Improvement may be achieved through a structured localised approach with multidisciplinary stakeholder involvement.

  5. Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain.

    Science.gov (United States)

    Taber, Louise; Lynch, Shau Yu; He, Ellie; Ripa, Steven R

    2016-01-01

    To evaluate long-term use of Hysingla(®) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain. This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naïve or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily. Supplemental nonopioid and short-acting opioid analgesics were permitted. This paper presents the results of 106 patients who continued HYD treatment for up to 76 weeks. Primary safety measures included the incidence of adverse events, as well as audiologic, clinical laboratory and electrocardiogram measurements. Effectiveness was measured by the change between baseline and the overall 76-week treatment period in "average pain over the last 24 h" (0 = no pain, 10 = pain as bad as you can imagine), Brief Pain Inventory-Short Form survey, Medical Outcomes Study 36-Item Short Form Health Survey, Medical Outcomes Study Sleep Scale-Revised and concomitant nonstudy opioid analgesic use. Among 410 patients who completed the maintenance period, 106 continued into the extension. Of these, 83 (78%) completed the entire 76-week treatment period. Treatment-emergent adverse events were typical of those observed with μ-opioid agonists. No study drug abuse or diversion was reported. Clinically important analgesia and functional improvement were achieved during the dose-titration period and were maintained in most patients throughout 76 weeks without the need for continued HYD dose increases or changes in concomitant nonstudy opioid analgesics. The mean pain score was 6.1 at baseline, 3.8 at the end of the dose titration period and 3.8 through 76 weeks. HYD was generally well tolerated. No unexpected safety concerns emerged. Pain control was sustained throughout 76 weeks of

  6. ONC201 kills breast cancer cells in vitro by targeting mitochondria.

    Science.gov (United States)

    Greer, Yoshimi Endo; Porat-Shliom, Natalie; Nagashima, Kunio; Stuelten, Christina; Crooks, Dan; Koparde, Vishal N; Gilbert, Samuel F; Islam, Celia; Ubaldini, Ashley; Ji, Yun; Gattinoni, Luca; Soheilian, Ferri; Wang, Xiantao; Hafner, Markus; Shetty, Jyoti; Tran, Bao; Jailwala, Parthav; Cam, Maggie; Lang, Martin; Voeller, Donna; Reinhold, William C; Rajapakse, Vinodh; Pommier, Yves; Weigert, Roberto; Linehan, W Marston; Lipkowitz, Stanley

    2018-04-06

    We report a novel mechanism of action of ONC201 as a mitochondria-targeting drug in cancer cells. ONC201 was originally identified as a small molecule that induces transcription of TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cancer cells by activating TRAIL death receptors. In this study, we examined ONC201 toxicity on multiple human breast and endometrial cancer cell lines. ONC201 attenuated cell viability in all cancer cell lines tested. Unexpectedly, ONC201 toxicity was not dependent on either TRAIL receptors nor caspases. Time-lapse live cell imaging revealed that ONC201 induces cell membrane ballooning followed by rupture, distinct from the morphology of cells undergoing apoptosis. Further investigation found that ONC201 induces phosphorylation of AMP-dependent kinase and ATP loss. Cytotoxicity and ATP depletion were significantly enhanced in the absence of glucose, suggesting that ONC201 targets mitochondrial respiration. Further analysis indicated that ONC201 indirectly inhibits mitochondrial respiration. Confocal and electron microscopic analysis demonstrated that ONC201 triggers mitochondrial structural damage and functional impairment. Moreover, ONC201 decreased mitochondrial DNA (mtDNA). RNAseq analysis revealed that ONC201 suppresses expression of multiple mtDNA-encoded genes and nuclear-encoded mitochondrial genes involved in oxidative phosphorylation and other mitochondrial functions. Importantly, fumarate hydratase deficient cancer cells and multiple cancer cell lines with reduced amounts of mtDNA were resistant to ONC201. These results indicate that cells not dependent on mitochondrial respiration are ONC201-resistant. Our data demonstrate that ONC201 kills cancer cells by disrupting mitochondrial function and further suggests that cancer cells that are dependent on glycolysis will be resistant to ONC201.

  7. Why still philosophy?: Once again

    Directory of Open Access Journals (Sweden)

    Krstić Predrag

    2007-01-01

    Full Text Available The intention of this paper is to revisit, once again the question asked by Adorno and Habermas and other contemporary thinkers under different headings few decades ago. The author is suggesting that nowadays philosophy requires a final departure from the idea of having single and perennial face, and that this would not only allow, but also enable philosophy to test its various faces freely, that is, without norm or limit set in advance. At the same time, by creating such ′liberal′ climate philosophy would no longer be frightened by the possible answer, and hence would no longer dramatize the very question of ′why still?′. Even if philosophy turns out to be far less than the mission it once bestowed upon itself.

  8. Efficacy and tolerability of rasagiline in daily clinical use--a post-marketing observational study in patients with Parkinson's disease.

    Science.gov (United States)

    Reichmann, H; Jost, W H

    2010-09-01

    The MAO-B inhibitor rasagiline is indicated for the treatment of idiopathic Parkinson's disease (PD), and its use is supported by evidence from large-scale, controlled clinical studies. The post-marketing observational study presented here investigated the efficacy and tolerability of rasagiline treatment (monotherapy or combination therapy) in daily clinical practice. The study included patients with idiopathic PD who received rasagiline (recommended dose 1 mg, once daily) as monotherapy or combination therapy. The treatment and observation period was approximately 4 months. Outcome measures included the change from baseline in the Columbia University Rating Scale (CURS), the Unified PD Rating Scale fluctuation subscale, daily OFF time (patient home diaries) and the PD Questionnaire-39. Adverse drug reactions/adverse events (ADRs/AEs) and the physician's global judgement of tolerability and efficacy were also examined. Overall, 754 patients received rasagiline during the study. Patients treated with rasagiline (monotherapy or combination therapy) showed significant improvements from baseline in symptom severity (including classical motor and non-classical motor/non-motor symptoms) and quality of life (QoL). Patients receiving combination therapy also experienced significant reductions in daily OFF time. Tolerability was rated as good/very good in over 90% of patients. In daily clinical practice, monotherapy or combination therapy with rasagiline is able to improve PD symptoms, reduce OFF time, and improve QoL, whilst demonstrating favourable tolerability. In addition, rasagiline has a simple dosing schedule of one tablet, once daily, with no titration. These results are consistent with the pivotal rasagiline clinical studies (TEMPO, LARGO and PRESTO).

  9. Meteorological Reference Years of Daily Mean Temperature during the Slighting Time

    International Nuclear Information System (INIS)

    Marchante Jimenez, M.; Ramirez Santigosa, L.; Navarro Fernandez, A.; Mora Lopez, L.; Sidrach de Cardona Ortin, M.

    2002-01-01

    In this work the characterization of the daily mean temperature during the sunlight time has been analyzed. An algorithm for the hourly series generation from extreme daily values has been applied to evaluate the daily mean temperature during the sunlight time. A generic algorithm has been enhanced as a function of the sunrise time. This algorithm allows taking into account the fractions related to the sunrise and sunset hours. This methodology has been applied in data from 45 Spanish stations, uniformly distributed in the Iberian Peninsula. Data for a period of 14 years has been used in most of locations, and once the interest variable has been calculated, the meteorological reference year of the daily mean temperature during the sunlight time has been evaluated in each stations. The next step is the evaluation of the daily mean temperature during the sunlight time in any point into the zone of evaluation, not only in the measured stations. From the result data in each measured station, an geographic information system has been used in order to calculate the interpolation, obtaining maps with a data each 5 km. for each of the 365 days of the year. Then, this results can be superposed with the solar radiation evaluation obtaining the input data for the sizing of the photovoltaic grid connected system in any point of the Spanish geography. (Author) 64 refs

  10. A new once-a-day fentanyl citrate patch (Fentos Tape) could be a new treatment option in patients with end-of-dose failure using a 72-h transdermal fentanyl matrix patch.

    Science.gov (United States)

    Koike, Kazuhiko; Terui, Takeshi; Nagasako, Tomokazu; Horiuchi, Iori; Machino, Takayuki; Kusakabe, Toshiro; Hirayama, Yasuo; Mihara, Hiroyoshi; Yamakage, Michiaki; Kato, Junji; Nishisato, Takuji; Ishitani, Kunihiko

    2016-03-01

    The recommended dosing interval for transdermal fentanyl is every 72 h. However, some patients will have "end-of-dose failure," which may be seen as an increase of episodes of severe pain flares at the third day after application of the patch. A new once-a-day fentanyl patch was developed in Japan since 2010. This study aimed to assess the efficacy of the once-a-day fentanyl citrate patch for patients with cancer-related pain receiving the 72-h transdermal fentanyl not lasting 72 h. We performed a cross-sectional retrospective analysis of 445 inpatients with the 72-h transdermal fentanyl at Higashi Sapporo Hospital. We could switch to the once-a-day fentanyl citrate patch if patients reported inadequate pain relief beyond 48 h after application of the 72-h transdermal fentanyl. Patients recorded baseline scores for background pain intensity (PI) and the frequency of use of daily rescue medication for breakthrough cancer pain (BTcP). Of all patients, 10.1% showed the increase in PI of 30% or more baseline PI on the third day after application of the 72-h transdermal fentanyl. Of patients, 84.4% were converted from equivalent dose of the 72-h transdermal fentanyl to the once-a-day fentanyl citrate patch. On the third day after switching, 60.5% of patients showed a reduction of more than 30% from baseline PI. Switching to the once-a-day fentanyl citrate patch significantly reduced the mean frequency of daily rescue dose for BTcP. A once-a-day fentanyl citrate patch provided stable pain control. Its use may be considered as the dominant strategy for patients receiving a 72-h transdermal fentanyl not lasting 72 h.

  11. Daily snow depth measurements from 195 stations in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Allison, L.J. [ed.] [Oak Ridge National Lab., TN (United States). Carbon Dioxide Information Analysis Center; Easterling, D.R.; Jamason, P.; Bowman, D.P.; Hughes, P.Y.; Mason, E.H. [National Oceanic and Atmospheric Administration, Asheville, NC (United States). National Climatic Data Center

    1997-02-01

    This document describes a database containing daily measurements of snow depth at 195 National Weather Service (NWS) first-order climatological stations in the United States. The data have been assembled and made available by the National Climatic Data Center (NCDC) in Asheville, North Carolina. The 195 stations encompass 388 unique sampling locations in 48 of the 50 states; no observations from Delaware or Hawaii are included in the database. Station selection criteria emphasized the quality and length of station records while seeking to provide a network with good geographic coverage. Snow depth at the 388 locations was measured once per day on ground open to the sky. The daily snow depth is the total depth of the snow on the ground at measurement time. The time period covered by the database is 1893--1992; however, not all station records encompass the complete period. While a station record ideally should contain daily data for at least the seven winter months (January through April and October through December), not all stations have complete records. Each logical record in the snow depth database contains one station`s daily data values for a period of one month, including data source, measurement, and quality flags.

  12. A prospective randomized trial of hyperfractionated versus conventional once daily radiation for advanced squamous cell carcinomas of the larynx and pharynx

    International Nuclear Information System (INIS)

    Cummings, B.J.; Keane, T.J.; Pintilie, M.; O'Sullivan, B.; Payne, D.; Warde, P.; McLean, M.; Waldron, J.; Liu, F.-F.; Gullane, P.

    1996-01-01

    Purpose: To examine the effects of an increased dose of radiation therapy (RT) delivered by a hyperfractionated schedule compared to conventional once daily RT on toxicity, locoregional control and survival in the treatment of squamous cell carcinomas (SCC) of the larynx and pharynx. Materials/Methods: Between 1988 and 1995 336 patients were randomized to receive RT with curative intent. Eligible patients had biopsy proven SCC of the larynx or pharynx, with TN stages (AJC-UICC 1987) T3 or T4 N0, or any T with any N+. All patients were M0. Patients were stratified by site (larynx/oropharynx/hypopharynx), node status (clinically positive/negative), and performance status. Patients were treated with either 51 Gy TAD/20 fractions/4 wk (2.55 Gy 1x/d, conventional RT=CRT) or 58 Gy TAD/40 fractions/4 wk (1.45 Gy 2x/d, hyperfractionated RT=HFRT). Patients underwent EUA and selective biopsies 10 wk after RT; surgical salvage was performed for residual or recurrent cancer whenever possible. Results: The primary cancer arose in the oropharynx (138), larynx (133) or hypopharynx (65). T stages were distributed T1 22, T2 72, T3 133 and T4 109. N stage distribution was N0 127, N1 74, N2 117 and N3 18. The proportion of patients with acute mucosal toxicity (RTOG Grade 3 or 4) was increased by HFRT (60% versus 40%), but other acute and late toxicity was not significantly different. There was no difference in the incidence of morbidity in the two treatment groups in those who underwent surgery following RT. The locoregional control rates at 3 yrs for all cases were 45% (HFRT) vs 40% (CRT) log rank p=0.16; for primary tumors <4 cm 54% (HFRT) vs 42% (CRT) p=0.04; for primary tumors ≥ 4 cm 38% (HFRT) vs 41% (CRT) p=0.73. Local control was improved to some extent in SCC which arose in all sites, but most noticeably in hypopharyngeal cancers. The disease free survival rates at 3 yr for all cases were 37% (HFRT) vs 30% (CRT) p=0.15; for primary tumors < 4 cm 47% (HFRT) vs 34% (CRT) p=0

  13. What Is the Most Effective Way of Increasing the Bioavailability of Dietary Long Chain Omega-3 Fatty Acids—Daily vs. Weekly Administration of Fish Oil?

    Directory of Open Access Journals (Sweden)

    Samaneh Ghasemifard

    2015-07-01

    Full Text Available The recommendations on the intake of long chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFA vary from eating oily fish (“once to twice per week” to consuming specified daily amounts of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA (“250–500 mg per day”. It is not known if there is a difference in the uptake/bioavailability between regular daily consumption of supplementsvs. consuming fish once or twice per week. In this study, the bioavailability of a daily dose of n-3 LC-PUFA (Constant treatment, representing supplements, vs. a large weekly dose of n-3 LC-PUFA (Spike treatment, representing consuming once or twice per week, was assessed. Six-week old healthy male Sprague-Dawley rats were fed either a Constant treatment, a Spike treatment or Control treatment (no n-3 LC-PUFA, for six weeks. The whole body, tissues and faeces were analysed for fatty acid content. The results showed that the major metabolic fate of the n-3 LC-PUFA (EPA+docosapentaenoic acid (DPA + DHA was towards catabolism (β-oxidation accounting for over 70% of total dietary intake, whereas deposition accounted less than 25% of total dietary intake. It was found that significantly more n-3 LC-PUFA were β-oxidised when originating from the Constant treatment (84% of dose, compared with the Spike treatment (75% of dose. Conversely, it was found that significantly more n-3 LC-PUFA were deposited when originating from the Spike treatment (23% of dose, than from the Constant treatment (15% of dose. These unexpected findings show that a large dose of n-3 LC-PUFA once per week is more effective in increasing whole body n-3 LC-PUFA content in rats compared with a smaller dose delivered daily.

  14. Effect of Direct-to-Consumer Advertising on Asthma Medication Sales and Healthcare Use.

    Science.gov (United States)

    Daubresse, Matthew; Hutfless, Susan; Kim, Yoonsang; Kornfield, Rachel; Qato, Dima M; Huang, Jidong; Miller, Kay; Emery, Sherry L; Alexander, G Caleb

    2015-07-01

    The United States is one of only two countries that permit direct-to-consumer advertising (DTCA) of prescription drugs, and many questions remain regarding its effects. To quantify the association between asthma-related DTCA, pharmacy sales, and healthcare use. This was an ecological study from 2005 through 2009 using linked data from Nielsen (DTCA television ratings), the IMS Health National Prescription Audit (pharmacy sales), and the MarketScan Commercial Claims data (healthcare use) for 75 designated market areas in the United States. We used multilevel Poisson regression to model the relationship between DTCA and rates of prescriptions and use within and across designated market areas. Main outcome measures include (1) volume of total, new, and refilled prescriptions for advertised products based on pharmacy sales; (2) prescription claims for asthma medications; and asthma-related (3) emergency department use, (4) hospitalizations, and (5) outpatient encounters among the commercially insured. Four Food and Drug Administration-approved asthma medicines were advertised during the period examined: (1) fluticasone/salmeterol (Advair), (2) mometasone furoate (Asmanex), (3) montelukast (Singulair), and (4) budesonide/formoterol (Symbicort). After adjustment, each additional televised advertisement was associated with 2% (incident rate ratio, 1.02; 95% confidence interval, 1.01-1.03) higher pharmacy sales rate from 2005 through 2009, although this effect varied across the three consistently advertised therapies examined. Among the commercially insured, DTCA was positively and significantly associated with emergency room visits related to asthma (incident rate ratio, 1.02; 95% confidence interval, 1.01-1.04), but there was no relationship with hospitalizations or outpatient encounters. Among this population, DTCA was associated with higher prescription sales and asthma-related emergency department use.

  15. Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM: Crossover pilot study (J-VICTORIA study

    Directory of Open Access Journals (Sweden)

    Sakamoto Masaya

    2012-08-01

    Full Text Available Abstract Background No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM and cardiovascular parameters. Methods Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1 mean (± standard deviation 24-hour blood glucose level, 2 mean amplitude of glycemic excursions (MAGE, 3 fasting blood glucose level, 4 highest postprandial blood glucose level and time, 5 increase in blood glucose level after each meal, 6 area under the curve (AUC for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7 area over the curve (AOC for daily blood glucose level Results The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012. In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040, the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015, the AUC (≥180 mg/dL within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025, and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008 than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. Conclusions CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There

  16. Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): Crossover pilot study (J-VICTORIA study)

    Science.gov (United States)

    2012-01-01

    Background No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters. Methods Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. Conclusions CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and

  17. CHEMOTHERAPY-INDUCED NEUTROPENIA IN HIV POSITIVE PATIENTS WITH LYMPHOMA: COMPARISON OF PEGFILGRASTIM WITH DAILY FILGRASTIM ADMINISTRATION.

    Directory of Open Access Journals (Sweden)

    Luciana Teofili

    2012-01-01

    Full Text Available

    We retrospectively compared the incidence of neutropenia  in two groups of  HIV patients with lymphoma,  who underwent chemotherapy supported by once-per-cycle administration of pegfilgrastim or by daily subcutaneous injection of filgrastim, respectively. Our findings indicate that pegfilgrastim and filgastrim produce similar results in preventing both neutropenia and febrile neutropenia.

  18. CHEMOTHERAPY-INDUCED NEUTROPENIA IN HIV POSITIVE PATIENTS WITH LYMPHOMA: COMPARISON OF PEGFILGRASTIM WITH DAILY FILGRASTIM ADMINISTRATION.

    Directory of Open Access Journals (Sweden)

    Luciana Teofili

    2012-10-01

    Full Text Available We retrospectively compared the incidence of neutropenia  in two groups of  HIV patients with lymphoma,  who underwent chemotherapy supported by once-per-cycle administration of pegfilgrastim or by daily subcutaneous injection of filgrastim, respectively. Our findings indicate that pegfilgrastim and filgastrim produce similar results in preventing both neutropenia and febrile neutropenia.

  19. Protostar Evolution in the Orion Nebula Cluster (ONC)

    Science.gov (United States)

    Sanchez, Michael Allan

    2018-01-01

    We present our preliminary analysis of the protostars within the Orion Nebula Cluster (ONC). We developed a pipeline to identify protostars in the ONC using the IRAC instrument aboard Spitzer. We verified our photometric measurements with the catalog provided by Megeath et al. (2012). We then classified the protostar evolution stages (0/I, Flatt, II, and III) based on their spectral slope.

  20. Estimating the real world daily usage and cost for exenatide twice daily and liraglutide in Germany, the Netherlands, and the UK based on volumes dispensed by pharmacies

    Directory of Open Access Journals (Sweden)

    McDonell AL

    2015-01-01

    Full Text Available Amanda L McDonell,1 Urpo Kiiskinen,2 Danielle C Zammit,3 Robert W Kotchie,1 Per-Olof Thuresson,3 Claudia Nicolay,4 Thomas Haslam,1 Michiel Bruinsma,5 Anne-Jeanine Janszen-Van Oosterhout,6 Thorsten Otto41IMS Health, London, UK; 2Eli Lilly and Company, Helsinki, Finland; 3IMS Health, Basel, Switzerland; 4Eli Lilly and Company, Bad Homburg, Germany; 5IMS Health, Rotterdam, the Netherlands; 6Eli Lilly Nederland, Houten, the NetherlandsBackground: Glucagon-like peptide-1 (GLP-1 receptor agonists are indicated for improvement of glycemic control in adults with type 2 diabetes. Cost is one aspect of treatment to be considered, in addition to clinical benefits, when selecting optimal therapy for a patient. The objective of this study was to estimate the average dose usage and real world daily cost of the GLP-1 receptor agonists, exenatide twice daily and liraglutide once daily, in Germany, the Netherlands, and the UK.Methods: Administrative databases were used to source the data from longitudinal records of dispensed prescriptions. Data were extracted from the IMS Longitudinal Prescription database which captures details of prescriptions dispensed in pharmacies. Information on the dispensed quantity of each product was used to estimate average daily usage per patient. Daily dose usage was multiplied by the public price per unit to estimate daily cost.Results: The dispensed volume in Germany corresponded to a mean dispensed daily dose of 16.81 µg for exenatide twice daily and 1.37 mg for liraglutide (mean daily cost €4.02 and €4.54, respectively. In the Netherlands, average dispensed daily doses of 17.07 µg and 1.49 mg were observed for exenatide twice daily and liraglutide (mean daily cost €3.05 and €3.97, respectively. In the UK, the mean dispensed volume corresponded to a daily usage of 20.49 µg for exenatide twice daily and 1.50 mg for liraglutide (mean daily cost £2.53 and £3.28, respectively.Conclusion: Estimates of average daily

  1. Sexual objectification in women's daily lives: A smartphone ecological momentary assessment study.

    Science.gov (United States)

    Holland, Elise; Koval, Peter; Stratemeyer, Michelle; Thomson, Fiona; Haslam, Nick

    2017-06-01

    Sexual objectification, particularly of young women, is highly prevalent in modern industrialized societies. Although there is plenty of experimental and cross-sectional research on objectification, prospective studies investigating the prevalence and psychological impact of objectifying events in daily life are scarce. We used ecological momentary assessment to track the occurrence of objectifying events over 1 week in the daily lives of young women (N = 81). Participants reported being targeted by a sexually objectifying event - most often the objectifying gaze - approximately once every 2 days and reported witnessing sexual objectification of others approximately 1.35 times per day. Further, multilevel linear regression analyses showed that being targeted by sexual objectification was associated with a substantial increase in state self-objectification. Overall, individual differences had little impact in moderating these effects. © 2016 The British Psychological Society.

  2. Discovery and clinical introduction of first-in-class imipridone ONC201.

    Science.gov (United States)

    Allen, Joshua E; Kline, C Leah B; Prabhu, Varun V; Wagner, Jessica; Ishizawa, Jo; Madhukar, Neel; Lev, Avital; Baumeister, Marie; Zhou, Lanlan; Lulla, Amriti; Stogniew, Martin; Schalop, Lee; Benes, Cyril; Kaufman, Howard L; Pottorf, Richard S; Nallaganchu, B Rao; Olson, Gary L; Al-Mulla, Fahd; Duvic, Madeleine; Wu, Gen Sheng; Dicker, David T; Talekar, Mala K; Lim, Bora; Elemento, Olivier; Oster, Wolfgang; Bertino, Joseph; Flaherty, Keith; Wang, Michael L; Borthakur, Gautam; Andreeff, Michael; Stein, Mark; El-Deiry, Wafik S

    2016-11-08

    ONC201 is the founding member of a novel class of anti-cancer compounds called imipridones that is currently in Phase II clinical trials in multiple advanced cancers. Since the discovery of ONC201 as a p53-independent inducer of TRAIL gene transcription, preclinical studies have determined that ONC201 has anti-proliferative and pro-apoptotic effects against a broad range of tumor cells but not normal cells. The mechanism of action of ONC201 involves engagement of PERK-independent activation of the integrated stress response, leading to tumor upregulation of DR5 and dual Akt/ERK inactivation, and consequent Foxo3a activation leading to upregulation of the death ligand TRAIL. ONC201 is orally active with infrequent dosing in animals models, causes sustained pharmacodynamic effects, and is not genotoxic. The first-in-human clinical trial of ONC201 in advanced aggressive refractory solid tumors confirmed that ONC201 is exceptionally well-tolerated and established the recommended phase II dose of 625 mg administered orally every three weeks defined by drug exposure comparable to efficacious levels in preclinical models. Clinical trials are evaluating the single agent efficacy of ONC201 in multiple solid tumors and hematological malignancies and exploring alternative dosing regimens. In addition, chemical analogs that have shown promise in other oncology indications are in pre-clinical development. In summary, the imipridone family that comprises ONC201 and its chemical analogs represent a new class of anti-cancer therapy with a unique mechanism of action being translated in ongoing clinical trials.

  3. ONC201 induces cell death in pediatric non-Hodgkin's lymphoma cells.

    Science.gov (United States)

    Talekar, Mala K; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S

    2015-08-03

    ONC201/TIC10 is a small molecule initially discovered by its ability to coordinately induce and activate the TRAIL pathway selectively in tumor cells and has recently entered clinical trials in adult advanced cancers. The anti-tumor activity of ONC201 has previously been demonstrated in several preclinical models of cancer, including refractory solid tumors and a transgenic lymphoma mouse model. Based on the need for new safe and effective therapies in pediatric non-Hodgkin's lymphoma (NHL) and the non-toxic preclinical profile of ONC201, we investigated the in vitro efficacy of ONC201 in non-Hodgkin's lymphoma (NHL) cell lines to evaluate its therapeutic potential for this disease. ONC201 caused a dose-dependent reduction in the cell viability of NHL cell lines that resulted from induction of apoptosis. As expected from prior observations, induction of TRAIL and its receptor DR5 was also observed in these cell lines. Furthermore, dual induction of TRAIL and DR5 appeared to drive the observed apoptosis and TRAIL expression was correlated linearly with sub-G1 DNA content, suggesting its potential role as a biomarker of tumor response to ONC201-treated lymphoma cells. We further investigated combinations of ONC201 with approved chemotherapeutic agents used to treat lymphoma. ONC201 exhibited synergy in combination with the anti-metabolic agent cytarabine in vitro, in addition to cooperating with other therapies. Together these findings indicate that ONC201 is an effective TRAIL pathway-inducer as a monoagent that can be combined with chemotherapy to enhance therapeutic responses in pediatric NHL.

  4. A reversible albumin-binding growth hormone derivative is well tolerated and possesses a potential once-weekly treatment profile.

    Science.gov (United States)

    Rasmussen, Michael Højby; Olsen, Minna W Brændholt; Alifrangis, Lene; Klim, Søren; Suntum, Mette

    2014-10-01

    Human growth hormone (hGH) replacement therapy currently requires daily sc injections for years/lifetime, which may be both inconvenient and distressing for patients. NNC0195-0092 is a novel hGH derivative intended for once-weekly treatment of GH deficiency. A noncovalent albumin binding moiety is attached to the hGH backbone. Clearance is reduced as a consequence of a reversible binding to circulating serum albumin, which prolongs the pharmacodynamic (PD) effect. To evaluate safety, local tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose (SD) and multiple doses (MD) of NNC0195-0092. Randomized, single-center, placebo-controlled, double-blind, SD/MD, dose-escalation trial of 105 healthy male subjects. NNC0195-0092 sc administration: Five cohorts of eight subjects received one dose of NNC0195-0092 (0.01-0.32 mg/kg) (n = 6) or placebo (n = 2). Sixteen subjects (equal numbers of Japanese and non-Asian) received once-weekly doses of NNC0195-0092 (0.02-0.24 mg/kg; n=12) or placebo (n=4) for 4 weeks. Blood samples were drawn for assessment of safety, PK, IGF-1, and IGF binding protein 3 profiles and anti-drug antibodies. SD and MD of NNC0195-0092 were well tolerated at all dose levels. No safety concerns or local tolerability issues were identified. A dose-dependent IGF-1 response was observed. IGF-1 profiles suggest that NNC0195-0092 may be suitable for once-weekly dosing, with a clinically relevant dose ≤0.08 mg/kg/week. No differences in PK and PD were observed between Japanese and non-Asian subjects. SD and MD of NNC0195-0092 administered to healthy Japanese and non-Asian male subjects were well tolerated at all doses. The present trial suggests that NNC0195-0092 has the potential for an efficacious, well-tolerated, once-weekly GH treatment.

  5. mTOR inhibition sensitizes ONC201-induced anti-colorectal cancer cell activity.

    Science.gov (United States)

    Jin, Zhe-Zhu; Wang, Wei; Fang, Di-Long; Jin, Yong-Jun

    2016-09-30

    We here tested the anti-colorectal cancer (CRC) activity by a first-in-class small molecule TRAIL inducer ONC201. The potential effect of mTOR on ONC201's actions was also examined. ONC201 induced moderate cytotoxicity against CRC cell lines (HT-29, HCT-116 and DLD-1) and primary human CRC cells. Significantly, AZD-8055, a mTOR kinase inhibitor, sensitized ONC201-induced cytotoxicity in CRC cells. Meanwhile, ONC201-induced TRAIL/death receptor-5 (DR-5) expression, caspase-8 activation and CRC cell apoptosis were also potentiated with AZD-8055 co-treatment. Reversely, TRAIL sequestering antibody RIK-2 or the caspase-8 specific inhibitor z-IETD-fmk attenuated AZD-8055 plus ONC201-induced CRC cell death. Further, mTOR kinase-dead mutation (Asp-2338-Ala) or shRNA knockdown significantly sensitized ONC201's activity in CRC cells, leading to profound cell death and apoptosis. On the other hand, expression of a constitutively-active S6K1 (T389E) attenuated ONC201-induced CRC cell apoptosis. For the mechanism study, we showed that ONC201 blocked Akt, but only slightly inhibited mTOR in CRC cells. Co-treatment with AZD-8055 also concurrently blocked mTOR activation. These results suggest that mTOR could be a primary resistance factor of ONC201 in CRC cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Role of Dopamine Receptors in the Anticancer Activity of ONC201.

    Science.gov (United States)

    Kline, Christina Leah B; Ralff, Marie D; Lulla, Amriti R; Wagner, Jessica M; Abbosh, Phillip H; Dicker, David T; Allen, Joshua E; El-Deiry, Wafik S

    2018-01-01

    ONC201/TIC10 is a first-in-class small molecule inducer of TRAIL that causes early activation of the integrated stress response. Its promising safety profile and broad-spectrum efficacy in vitro have been confirmed in Phase I/II trials in several advanced malignancies. Binding and reporter assays have shown that ONC201 is a selective antagonist of the dopamine D2-like receptors, specifically, DRD2 and DRD3. We hypothesized that ONC201's interaction with DRD2 plays a role in ONC201's anticancer effects. Using cBioportal and quantitative reverse-transcription polymerase chain reaction analyses, we confirmed that DRD2 is expressed in different cancer cell types in a cell type-specific manner. On the other hand, DRD3 was generally not detectable. Overexpressing DRD2 in cells with low DRD2 levels increased ONC201-induced PARP cleavage, which was preceded and correlated with an increase in ONC201-induced CHOP mRNA expression. On the other hand, knocking out DRD2 using CRISPR/Cas9 in three cancer cell lines was not sufficient to abrogate ONC201's anticancer effects. Although ONC201's anticancer activity was not dependent on DRD2 expression in the cancer cell types tested, we assessed the cytotoxic potential of DRD2 blockade. Transient DRD2 knockdown in HCT116 cells activated the integrated stress response and reduced cell number. Pharmacological antagonism of DRD2 significantly reduced cell viability. Thus, we demonstrate in this study that disrupting dopamine receptor expression and activity can have cytotoxic effects that may at least be in part due to the activation of the integrated stress response. On the other hand, ONC201's anticancer activity goes beyond its ability to antagonize DRD2, potentially due to ONC201's ability to activate other pathways that are independent of DRD2. Nevertheless, blocking the dopamine D1-like receptor DRD5 via siRNA or the use of a pharmacological antagonist promoted ONC201-induced anticancer activity. Copyright © 2018 The Authors

  7. Role of Dopamine Receptors in the Anticancer Activity of ONC201

    Directory of Open Access Journals (Sweden)

    Christina Leah B. Kline

    2018-01-01

    Full Text Available ONC201/TIC10 is a first-in-class small molecule inducer of TRAIL that causes early activation of the integrated stress response. Its promising safety profile and broad-spectrum efficacy in vitro have been confirmed in Phase I/II trials in several advanced malignancies. Binding and reporter assays have shown that ONC201 is a selective antagonist of the dopamine D2-like receptors, specifically, DRD2 and DRD3. We hypothesized that ONC201’s interaction with DRD2 plays a role in ONC201’s anticancer effects. Using cBioportal and quantitative reverse-transcription polymerase chain reaction analyses, we confirmed that DRD2 is expressed in different cancer cell types in a cell type–specific manner. On the other hand, DRD3 was generally not detectable. Overexpressing DRD2 in cells with low DRD2 levels increased ONC201-induced PARP cleavage, which was preceded and correlated with an increase in ONC201-induced CHOP mRNA expression. On the other hand, knocking out DRD2 using CRISPR/Cas9 in three cancer cell lines was not sufficient to abrogate ONC201’s anticancer effects. Although ONC201’s anticancer activity was not dependent on DRD2 expression in the cancer cell types tested, we assessed the cytotoxic potential of DRD2 blockade. Transient DRD2 knockdown in HCT116 cells activated the integrated stress response and reduced cell number. Pharmacological antagonism of DRD2 significantly reduced cell viability. Thus, we demonstrate in this study that disrupting dopamine receptor expression and activity can have cytotoxic effects that may at least be in part due to the activation of the integrated stress response. On the other hand, ONC201’s anticancer activity goes beyond its ability to antagonize DRD2, potentially due to ONC201’s ability to activate other pathways that are independent of DRD2. Nevertheless, blocking the dopamine D1-like receptor DRD5 via siRNA or the use of a pharmacological antagonist promoted ONC201-induced anticancer activity.

  8. 45 CFR 170.423 - Principles of proper conduct for ONC-ATCBs.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Principles of proper conduct for ONC-ATCBs. 170... § 170.423 Principles of proper conduct for ONC-ATCBs. An ONC-ATCB shall: (a) Operate its certification... EHR Module developer conspicuously include the following text on its Web site and in all marketing...

  9. Global Historical Climatology Network - Daily (GHCN-Daily), Version 3

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Global Historical Climatology Network - Daily (GHCN-Daily) dataset integrates daily climate observations from approximately 30 different data sources. Version 3...

  10. Computational fluid dynamics: a suitable assessment tool for demonstrating the antiobstructive effect of drugs in the therapy of allergic rhinitis.

    Science.gov (United States)

    Achilles, N; Pasch, N; Lintermann, A; Schröder, W; Mösges, R

    2013-02-01

    This systematic review aims first to summarize the previous areas of application of computational fluid dynamics (CFD) and then to demonstrate that CFD is also a suitable instrument for generating three-dimensional images that depict drug effects on nasal mucosa. Special emphasis is placed on the three-dimensional visualization of the antiobstructive effect of nasal steroids and antihistamines in the treatment of allergic rhinitis. In the beginning, CFD technology was only used to demonstrate physiological and pathophysiological airflow conditions in the nose and to aid in preoperative planning and postoperative monitoring of surgical outcome in the field of rhinosurgery. The first studies using CFD examined nasal respiratory physiology, important functions of the nose, such as conditioning and warming of inspired air, and the influence of pathophysiological changes on nasal breathing. Also, postoperative outcome of surgical procedures could be "predicted" using the nasal airflow model. Later studies focused on the three-dimensional visualization of the effect of nasal sprays in healthy subjects and postoperative patients. A completely new approach, however, was the use of CFD in the area of allergic rhinitis and the treatment of its cardinal symptom of nasal obstruction. In two clinical trials, a suitable patient with a positive history of allergic rhinitis was enrolled during a symptom-free period after the pollen season. The patient developed typical allergic rhinitis symptoms after provocation with birch pollen. The 3-D visualization showed that the antiallergic treatment successfully counteracted the effects of nasal allergen provocation on nasal airflow. These observations were attributed to the antiobstructive effect of a nasal steroid (mometasone furoate) and a systemic antihistamine (levocetirizine), respectively. CFD therefore constitutes a non-invasive, precise, reliable and objective examination procedure for generating three-dimensional images that

  11. Effect of Direct-to-Consumer Advertising on Asthma Medication Sales and Healthcare Use

    Science.gov (United States)

    Daubresse, Matthew; Hutfless, Susan; Kim, Yoonsang; Kornfield, Rachel; Qato, Dima M.; Huang, Jidong; Miller, Kay; Emery, Sherry L.

    2015-01-01

    Rationale: The United States is one of only two countries that permit direct-to-consumer advertising (DTCA) of prescription drugs, and many questions remain regarding its effects. Objectives: To quantify the association between asthma-related DTCA, pharmacy sales, and healthcare use. Methods: This was an ecological study from 2005 through 2009 using linked data from Nielsen (DTCA television ratings), the IMS Health National Prescription Audit (pharmacy sales), and the MarketScan Commercial Claims data (healthcare use) for 75 designated market areas in the United States. We used multilevel Poisson regression to model the relationship between DTCA and rates of prescriptions and use within and across designated market areas. Main outcome measures include (1) volume of total, new, and refilled prescriptions for advertised products based on pharmacy sales; (2) prescription claims for asthma medications; and asthma-related (3) emergency department use, (4) hospitalizations, and (5) outpatient encounters among the commercially insured. Measurements and Main Results: Four Food and Drug Administration–approved asthma medicines were advertised during the period examined: (1) fluticasone/salmeterol (Advair), (2) mometasone furoate (Asmanex), (3) montelukast (Singulair), and (4) budesonide/formoterol (Symbicort). After adjustment, each additional televised advertisement was associated with 2% (incident rate ratio, 1.02; 95% confidence interval, 1.01–1.03) higher pharmacy sales rate from 2005 through 2009, although this effect varied across the three consistently advertised therapies examined. Among the commercially insured, DTCA was positively and significantly associated with emergency room visits related to asthma (incident rate ratio, 1.02; 95% confidence interval, 1.01–1.04), but there was no relationship with hospitalizations or outpatient encounters. Conclusions: Among this population, DTCA was associated with higher prescription sales and asthma-related emergency

  12. SEZARY SYNDROME MIMICKING GENERALIZED PSORIASIS VULGARIS

    Directory of Open Access Journals (Sweden)

    Eko Rianova Lynoora

    2016-09-01

    Full Text Available Sezary syndrome is the leukemic variant of cutaneous T cell lymphoma. This disease is characterized by some reddish patches or plaques all over the skin which extends to the whole body into erythroderma, lymphadenopathy. It is also indicated by the presence of atypical lymphocytes called Sezary cells. This case report is aimed to know clinical manifestation, examination and management of Sezary syndrome which clinically resembles generalized psoriasis. A 60 years old man came with scaly reddish brown plaques almost all over his body. It was accompanied by lymphadenopathy on the supraclavicular lymph node right and left as well as intense itchy. Other clinical features were alopecia, palmoplantar hyperkeratosis, onychodysthropy, facies leonine without anesthesia on the lesion and enlargement of peripheral nerve. From a laboratory test, an increase in the number of leukocytes and, Sezary cells were found in peripheral blood smear examination; while the histopathology showed focal athrophy and acanthosis of the epidermis and dense infiltration of lymphocytes in the dermo-epidermal junction and superficial dermis. Patient received 3 x 5 mg (1 cycle of methotrexate (MTX with 0,1% cream mometasone furoate and 3x1 tablet of CTM for adjunctive therapy. Methotrexate was discontinued because there was a disturbance in liver function and deterioration of patient’s condition. After 25 days of treatment, the patient got sepsis and then passed away. Early onset of Sezary syndrome in this case is difficult to know because the clinical manifestation is similar with psoriasis vulgaris. Supporting examination such as laboratory test, blood smears and histopathology examination could help the diagnosis. The presence of lymphadenopathy, and atypical lymphocytes in the peripheral blood and the extensive skin involvement reflect the poor prognosis. The most common cause of death was sepsis.

  13. Effects of daily pyrantel tartrate on strongylid population dynamics and performance parameters of young horses repeatedly infected with cyathostomins and Strongylus vulgaris.

    Science.gov (United States)

    Reinemeyer, C R; Prado, J C; Andersen, U V; Nielsen, M K; Schricker, B; Kennedy, T

    2014-08-29

    Strongylid infections are ubiquitous in grazing horse populations. Infections with cyathostomin (small strongyle) and strongylin (large strongyle) nematodes have long been associated with clinical disease in horses, but little is known about their subclinical impact. A masked, randomized, controlled study was conducted to evaluate the effects of daily administration of pyrantel tartrate on body condition scores, weight gain, fecal egg counts, and total worm counts of young horses repeatedly inoculated with strongylid larvae. Twenty eight immature horses were treated with larvicidal anthelmintic regimens and randomly allocated to two groups. Group 1 horses were given a pelleted placebo product once daily, and those in Group 2 received pyrantel tartrate once daily at ∼ 2.64 mg/kg body weight. On five days during each week, ∼ 5000 infective cyathostomin larvae were administered to each horse. In addition, horses received ∼ 25 infective Strongylus vulgaris larvae once weekly. Horses were maintained on pasture for 154 days and had ad libitum access to grass hay throughout. At approximate, 14-day intervals, body weights were measured, body condition scores were assigned, fecal samples were collected for egg counts, and blood samples were collected for measurement of S. vulgaris antibodies and various physiologic parameters. After 22 weeks at pasture and 14-17 days in confinement, horses were euthanatized and necropsied. Nematodes were recovered and counted from aliquots of organ contents, representative samples of large intestinal mucosa, and the root of the cranial mesenteric artery. Daily treatment with pyrantel tartrate at the recommended dosage significantly reduced numbers of adult cyathostomins in the gut lumen and early third-stage larvae in the cecal mucosa, increased the proportions of fourth-stage larvae in the gut contents, and was accompanied by significant improvements in body condition scores. Fecal egg counts of horses receiving daily pyrantel

  14. Daily text messages used as a method for assessing low back pain among workers.

    Science.gov (United States)

    Burström, Lage; Jonsson, Håkan; Björ, Bodil; Hjalmarsson, Ulla; Nilsson, Tohr; Reuterwall, Christina; Wahlström, Jens

    2016-02-01

    To evaluate a method for collecting data concerning low back pain (LBP) using daily text messages and to characterize the reported LBP in terms of intensity, variability, and episodes. We conducted a cohort study of LBP among workers used by a mining company. The participants were asked to answer the question "How much pain have you had in your lower back in the last 24 hours on a scale from 0 to 10, where 0 = no pain and 10 = the worst pain imaginable" once a day for 5 weeks, with this process being repeated 6 months later. A total of 121 workers participated in the first period of data collection, and 108 participated in the second period. The daily response rate was 93% for both periods, and cluster analysis was shown to be a feasible statistical method for clustering LBP into subgroups of low, medium, and high pain. The daily text messages method also worked well for assessing the episodic nature of LBP. We have demonstrated a method for repeatedly measuring of LBP using daily text messages. The data permitted clustering into subgroups and could be used to define episodes of LBP. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Intent to Quit among Daily and Non-Daily College Student Smokers

    Science.gov (United States)

    Pinsker, E. A.; Berg, C. J.; Nehl, E. J.; Prokhorov, A. V.; Buchanan, T. S.; Ahluwalia, J. S.

    2013-01-01

    Given the high prevalence of young adult smoking, we examined (i) psychosocial factors and substance use among college students representing five smoking patterns and histories [non-smokers, quitters, native non-daily smokers (i.e. never daily smokers), converted non-daily smokers (i.e. former daily smokers) and daily smokers] and (ii) smoking…

  16. STRike - characteristics of HIV-1-infected patients treated with a single-tablet regimen in daily clinical practice

    OpenAIRE

    S Esser; H Heiken; L Gallo; S Schellberg; M Schlag; A Moll; R Pauli; A Stoehr; O Degen; H Jaeger; C Stephan; G Fätkenheuer

    2012-01-01

    The life-long antiretroviral treatment of HIV-1 infection requires effective and well tolerated medications complemented by high rates of adherence in order to achieve viral suppression, immunologic reconstitution and to prevent the development of resistance. Single-tablet regimens (STRs), combining a full antiretroviral regimen in one tablet taken once daily, have been designed to achieve high adherence and better long-term outcomes. “STRike” is the first cohort study, describi...

  17. Clinical efficacy and safety of a new 1000-mg suspension versus twice-daily 500-mg tablets of MPFF in patients with symptomatic chronic venous disorders: a randomized controlled trial.

    Science.gov (United States)

    Carpentier, Patrick; van Bellen, Bonno; Karetova, Debora; Hanafiah, Harunarashid; Enriquez-Vega, Elizabeth; Kirienko, Alexander; Dzupina, Andrej; Sabovic, Miso; Reina Gutierrez, Lourdes; Subwongcharoen, Somboom; Tüzün, Hasan; Maggioli, Arnaud

    2017-10-01

    Chronic venous disorders (CVD) is estimated to affect 30% to 50% of women and 10% to 30% of men. The most widely prescribed treatment for CVD worldwide is micronized purified flavonoid fraction 500 mg (MPFF). The aim of this clinical trial was to develop a new once daily 1000-mg oral suspension of MPFF. In an international, randomized, double-blind, parallel-group study, symptomatic individuals classified CEAP C0s to C4s were randomized in either treatment arm and treated for 8 weeks. Lower limb symptoms (discomfort, pain and heaviness) were assessed using Visual Analog Scales (VAS), and quality of life (QoL) was measured with the CIVIQ-20 Questionnaire. A total of 1139 patients were included in the study. Both MPFF treatment regimens were well tolerated and associated with a significant reduction in lower limb symptoms. A non-inferiority of MPFF 1000-mg oral suspension once daily compared to MPFF 500-mg tablet twice daily (P1000 mg and -3.37 cm for MPFF 500 mg), leg pain (-3.27 cm for MPFF 1000 mg and -3.31 cm for MPFF 500 mg) and leg heaviness (-3.41 cm for MPFF 1000 mg and -3.46 cm for MPFF 500 mg). The patients' QoL was improved by about 20 points on the CIVIQ scale in both groups (19.33 points for MPFF 1000 mg and 20.28 points for MPFF 500 mg). MPFF 1000-mg oral suspension and MPFF 500-mg tablets treatments were associated with similar reductions in lower limb symptoms and QoL improvement. The new once daily MPFF1000-mg oral suspension has a similar safety profile to two tablets of MPFF 500 mg, with the advantage of one daily intake, potentially associated with improved patient adherence and easier CVD management.

  18. Epoetin alfa 40000 U once weekly and intravenous iron supply in solid tumor patients: early increase of hemoglobin level during chemotherapy

    International Nuclear Information System (INIS)

    Lalle, M.; Antimi, M.; Pistillucci, G.; D'Aprile, M.

    2005-01-01

    The objective of this observational study was the early evaluation of the impact, a week after the first administration of epoetin alfa 40000 U once weekly and i.v. dose of 62.5 mg sodium ferric gluconate for seven days in improving hemoglobin levels in cancer patients affected by mild/moderate or severe anemia during chemotherapy. Twenty patients affected by solid tumors who received epoetin alfa 40000 U once weekly and daily i.v. sodium ferric gluconate for one week were evaluated: 90% of the patients showed hemoglobin increase, with a median level of hemoglobin increase of 0.73 g/L from baseline, and 50% of them showing a hemoglobin increase > 1 gr/L. The treatment was well tolerated and no adverse event was observed. The early increase of hemoglobin level from baseline is interesting and suggestive for the possibility of achieving an adequate hemoglobin level with a short-term treatment. It is still necessary to further explore the real need of iron supplementation to maintain adequate erythropoiesis prior and during epoetin therapy

  19. Effects of long-term moderate exercise and increase in number of daily steps on serum lipids in women: randomised controlled trial [ISRCTN21921919

    Directory of Open Access Journals (Sweden)

    Mirbod Seyed

    2002-01-01

    Full Text Available Abstract Background This study was designed to evaluate the effects of a 24-month period of moderate exercise on serum lipids in menopausal women. Methods The subjects (40–60 y were randomly divided into an exercise group (n = 14 and a control group (n = 13. The women in the exercise group were asked to participate in a 90-minute physical education class once a week and to record their daily steps as measured by a pedometer for 24 months. Results Mean of daily steps was significantly higher in the exercise group from about 6,800 to over 8,500 steps (P P Conclusions These results suggest that daily exercise as well as increasing the number of daily steps can improve the profile of serum lipids.

  20. Chronic and Daily Stressors Along With Negative Affect Interact to Predict Daily Tiredness.

    Science.gov (United States)

    Hartsell, Elizabeth N; Neupert, Shevaun D

    2017-11-01

    The present study examines the within-person relationship of daily stressors and tiredness and whether this depends on daily negative affect and individual differences in chronic stress. One hundred sixteen older adult participants were recruited via Amazon's Mechanical Turk for a 9-day daily diary study. Daily tiredness, daily stressors, and negative affect were measured each day, and chronic stress was measured at baseline. Daily stressors, daily negative affect, and chronic stress interacted to predict daily tiredness. People with high chronic stress who experienced an increase in daily negative affect were the most reactive to daily stressors in terms of experiencing an increase in daily tiredness. We also found that people with low levels of chronic stress were the most reactive to daily stressors when they experienced low levels of daily negative affect. Our results highlight the need for individualized and contextualized approaches to combating daily tiredness in older adults.

  1. Prolonged maintenance of capsaicin-induced hyperalgesia by brief daily vibration stimuli.

    Science.gov (United States)

    Kim, Hee Kee; Schattschneider, Jörn; Lee, Inhyung; Chung, Kyungsoon; Baron, Ralf; Chung, Jin Mo

    2007-05-01

    This study tests the hypothesis that central sensitization initiated by nociceptive input can be maintained by repeated brief innocuous peripheral inputs. Capsaicin was injected intradermally into the hind paw of adult rats. Three different types of daily cutaneous mechanical stimulations (vibration, soft brush, or pressure) were applied to the capsaicin-injected paw for a period of 2 weeks. Daily stimulation consisted of a 10-s stimulation repeated every 30s for 30 min. Foot withdrawal thresholds to von Frey stimuli applied to the paw were measured once a day for 4 weeks. The capsaicin-only group (control rats without daily stimulation) showed hyperalgesia lasting for 3 days. In contrast, hyperalgesia persisted for 2 weeks in the group that received vibration stimulation. Neither the soft brush nor the pressure group showed a significant difference in mechanical threshold from the control group (capsaicin only). The vibration-induced prolonged hyperalgesia was significantly reduced by systemic injection of ifenprodil, an NMDA-receptor antagonist, but it was not influenced by either an AMPA-receptor blocker or a reactive oxygen species (ROS) scavenger. Furthermore, a dorsal column lesion did not interfere with the prolongation of hyperalgesia. Data suggest that vibration-induced prolongation of hyperalgesia is mediated by spinal NMDA-receptors, and a similar mechanism may underlie some forms of chronic pain with no obvious causes, such as complex regional pain syndrome type 1 (CRPS-1).

  2. 45 CFR 170.440 - ONC-ATCB status.

    Science.gov (United States)

    2010-10-01

    ... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH INFORMATION TECHNOLOGY HEALTH INFORMATION TECHNOLOGY STANDARDS, IMPLEMENTATION SPECIFICATIONS, AND CERTIFICATION CRITERIA AND CERTIFICATION PROGRAMS FOR HEALTH INFORMATION TECHNOLOGY Temporary Certification Program for HIT § 170.440 ONC-ATCB status...

  3. Intent to quit among daily and non-daily college student smokers

    OpenAIRE

    Pinsker, E. A.; Berg, C. J.; Nehl, E. J.; Prokhorov, A. V.; Buchanan, T. S.; Ahluwalia, J. S.

    2012-01-01

    Given the high prevalence of young adult smoking, we examined (i) psychosocial factors and substance use among college students representing five smoking patterns and histories [non-smokers, quitters, native non-daily smokers (i.e. never daily smokers), converted non-daily smokers (i.e. former daily smokers) and daily smokers] and (ii) smoking category as it relates to readiness to quit among current smokers. Of the 4438 students at six Southeast colleges who completed an online survey, 69.7%...

  4. A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

    Science.gov (United States)

    Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

    2014-03-01

    The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  5. The effect of implementation strength of basic emergency obstetric and newborn care (BEmONC) on facility deliveries and the met need for BEmONC at the primary health care level in Ethiopia.

    Science.gov (United States)

    Tiruneh, Gizachew Tadele; Karim, Ali Mehryar; Avan, Bilal Iqbal; Zemichael, Nebreed Fesseha; Wereta, Tewabech Gebrekiristos; Wickremasinghe, Deepthi; Keweti, Zinar Nebi; Kebede, Zewditu; Betemariam, Wuleta Aklilu

    2018-05-02

    Basic emergency obstetric and newborn care (BEmONC) is a primary health care level initiative promoted in low- and middle-income countries to reduce maternal and newborn mortality. Tailored support, including BEmONC training to providers, mentoring and monitoring through supportive supervision, provision of equipment and supplies, strengthening referral linkages, and improving infection-prevention practice, was provided in a package of interventions to 134 health centers, covering 91 rural districts of Ethiopia to ensure timely BEmONC care. In recent years, there has been a growing interest in measuring program implementation strength to evaluate public health gains. To assess the effectiveness of the BEmONC initiative, this study measures its implementation strength and examines the effect of its variability across intervention health centers on the rate of facility deliveries and the met need for BEmONC. Before and after data from 134 intervention health centers were collected in April 2013 and July 2015. A BEmONC implementation strength index was constructed from seven input and five process indicators measured through observation, record review, and provider interview; while facility delivery rate and the met need for expected obstetric complications were measured from service statistics and patient records. We estimated the dose-response relationships between outcome and explanatory variables of interest using regression methods. The BEmONC implementation strength index score, which ranged between zero and 10, increased statistically significantly from 4.3 at baseline to 6.7 at follow-up (p < .05). Correspondingly, the health center delivery rate significantly increased from 24% to 56% (p < .05). There was a dose-response relationship between the explanatory and outcome variables. For every unit increase in BEmONC implementation strength score there was a corresponding average of 4.5 percentage points (95% confidence interval: 2.1-6.9) increase in

  6. Errorless (re)learning of daily living routines by a woman with impaired memory and initiation: transferrable to a new home?

    Science.gov (United States)

    Ferland, Mark B; Larente, Johanne; Rowland, Julia; Davidson, Patrick S R

    2013-01-01

    To use errorless learning to train a memory- and initiation-impaired woman on two activities of daily living routines and then to transfer these routines to a new home. Single case quasi-experimental. Over 9 months, a young woman with an anterior cerebral haemorrhagic stroke (secondary to a ruptured arteriovenous malformation) was trained on routines of morning self-care and diabetes management, involving extensive practice on a structured series of steps with intervention as needed to prevent errors. Once routines were established, family members were trained in the supervision and rating of the routines at home. Following discharge, caregivers continued to monitor the routines daily for 3 months. Errorless learning of self-care and diabetes routines was successful. The routines were transferred to a new home environment and maintained at a near perfect level over a 3-month follow-up period. The patient remained severely memory-impaired, indicating that her functional gains were not attributable to any recovery of her memory abilities over time. This case offers evidence that even people with severe memory and initiation impairments can be trained on new routines using errorless learning and that, once learned, these routines can be carried out in novel contexts.

  7. On Computational Power of Quantum Read-Once Branching Programs

    Directory of Open Access Journals (Sweden)

    Farid Ablayev

    2011-03-01

    Full Text Available In this paper we review our current results concerning the computational power of quantum read-once branching programs. First of all, based on the circuit presentation of quantum branching programs and our variant of quantum fingerprinting technique, we show that any Boolean function with linear polynomial presentation can be computed by a quantum read-once branching program using a relatively small (usually logarithmic in the size of input number of qubits. Then we show that the described class of Boolean functions is closed under the polynomial projections.

  8. Dynamic and control of a once through steam generator

    International Nuclear Information System (INIS)

    Gomes, Arivaldo Vicente

    1979-01-01

    This paper presents a non linear distributed parameter model for the dynamics and feedback control of a large countercurrent heat exchanger used as a once through steam generator for a breeder reactor power plant. A convergent, implicit method has been developed to solve simultaneously the equations of conservation of mass, momentum and energy. The model, applicable to heat exchanger systems in general, has been used specifically to study the performance of a once-through steam generator with respect to its load following ability and stability of throttle steam temperature and pressure. (author)

  9. Once a physicist: David Florence

    Science.gov (United States)

    Florence, David

    2009-03-01

    I did mathematical physics because it was just what I was best at. I enjoyed it at school, so I applied to do it at Nottingham University. I fell into it, to be quite honest. Once at university, I struggled at first, partly because I found it quite difficult to combine studying with competing and training in sport, which is pretty much full time as well. But by the end of my university career, I had learned to be organized, and to manage my time pretty effectively, so I enjoyed it a lot more.

  10. Once-through cycle, supercritical-pressure light water cooled reactor concept

    Energy Technology Data Exchange (ETDEWEB)

    Oka, Y.; Koshizuka, S. [Tokyo Univ., Tokai, Ibaraki (Japan). Nuclear Engineering Research Lab

    2001-07-01

    Concept of once-through cycle, supercritical-pressure light water cooled reactors was developed. The research covered major aspects of conceptual design such as cores of thermal and fast reactors, plant system and heat balance, safety system and criteria, accident and transient analysis, LOCA, PSA, plant control and start-up. The advantages of the reactor lie in the compactness of the plant from high specific enthalpy of supercritical water, the simplicity of the once-through cycle and the experiences of major component technologies which are based on supercritical fossil-fired power plants and LWRs. The operating temperatures of the major components are within the experience in spite of high coolant outlet temperature. The once-through cycle is compatible with the tight fuel lattice fast reactor because of high head pumps and small coolant flow rate. (author)

  11. Once-through cycle, supercritical-pressure light water cooled reactor concept

    International Nuclear Information System (INIS)

    Oka, Y.; Koshizuka, S.

    2001-01-01

    Concept of once-through cycle, supercritical-pressure light water cooled reactors was developed. The research covered major aspects of conceptual design such as cores of thermal and fast reactors, plant system and heat balance, safety system and criteria, accident and transient analysis, LOCA, PSA, plant control and start-up. The advantages of the reactor lie in the compactness of the plant from high specific enthalpy of supercritical water, the simplicity of the once-through cycle and the experiences of major component technologies which are based on supercritical fossil-fired power plants and LWRs. The operating temperatures of the major components are within the experience in spite of high coolant outlet temperature. The once-through cycle is compatible with the tight fuel lattice fast reactor because of high head pumps and small coolant flow rate. (author)

  12. ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer cells.

    Science.gov (United States)

    Yuan, Xun; Kho, Dhonghyo; Xu, Jing; Gajan, Ambikai; Wu, Kongming; Wu, Gen Sheng

    2017-03-28

    ONC201 was previously identified as a first-in-class antitumor agent and small-molecule inducer of the TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) gene that induces apoptosis in cancer cells. ONC201 has a safety profile and is currently in phase II clinical trials for the treatment of various malignancies. In the current study, we examine the effect of ONC201 on triple-negative breast cancer cells (TNBC), a subtype of breast cancer that is sensitive to TRAIL. We find that ONC201 inhibits the growth of TNBC cells including TNBC cells that have developed acquired TRAIL resistance. However, TNBC cells that have developed acquired ONC201 resistance are cross-resistant to TRAIL. Mechanistically, ONC201 triggers an integrated stress response (ISR) involving the activation of the transcription factor ATF4. Knockdown of ATF4 impairs ONC201-induced apoptosis of TNBC cells. Importantly, the activation of ATF4 is compromised in ONC201-resistant TNBC cells. Thus, our results indicate that ONC201 induces an ISR to cause TNBC cell death and suggest that TNBC patients may benefit from ONC201-based therapies.

  13. Mometasone Nasal Spray

    Science.gov (United States)

    ... nausea, or vomiting nosebleeds headache sore throat increased menstrual pain muscle or joint pain sinus pain weakness diarrhea ... weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and ...

  14. Development and in-vitro Evaluation of Once Daily Tablet Dosage ...

    African Journals Online (AJOL)

    Kuksal A, Tiwary AK, Jain NK, Jain S. Formulation and in vitro, in vivo evaluation of extended-release matrix tablet of zidovudine: influence of combination of hydrophilic and hydrophobic matrix formers. AAPS,. Pharm Sci Tech 2006; 7: 1-9. 6. Kumar R, Patil S, Patil MB, Patil SR, Paschapur MS. Design and In vitro Evaluation ...

  15. Do elderly people at more severe activity of daily living limitation stages fall more?

    Science.gov (United States)

    Henry-Sánchez, John T; Kurichi, Jibby E; Xie, Dawei; Pan, Qiang; Stineman, Margaret G

    2012-07-01

    The aim of this study was to explore how activity of daily living (ADL) stages and the perception of unmet needs for home accessibility features associate with a history of falling. Participants were from a nationally representative sample from the Second Longitudinal Survey of Aging conducted in 1994. The sample included 9250 community-dwelling persons 70 yrs or older. The associations of ADL stage and perception of unmet needs for home accessibility features with a history of falling within the past year (none, once, or multiple times) were explored after accounting for sociodemographic characteristics and comorbidities using a multinomial logistic regression model. The adjusted relative risk of falling more than once peaked at 4.30 (95% confidence interval, 3.29-5.61) for persons with severe limitation (ADL-III) compared those with no limitation (ADL-0) then declined for those at complete limitation (ADL-IV). The adjusted relative risks of falling once and multiple times were 1.42 (95% confidence interval, 1.07-1.87) and 1.85 (95% confidence interval, 1.44-2.36), respectively, for those lacking home accessibility features. Risk of falling appeared greatest for those whose homes lacked accessibility features and peaked at intermediate ADL limitation stages, presumably at a point when people have significant disabilities but sufficient function to remain partially active.

  16. Dose intensification of TRAIL-inducing ONC201 inhibits metastasis and promotes intratumoral NK cell recruitment.

    Science.gov (United States)

    Wagner, Jessica; Kline, C Leah; Zhou, Lanlan; Campbell, Kerry S; MacFarlane, Alexander W; Olszanski, Anthony J; Cai, Kathy Q; Hensley, Harvey H; Ross, Eric A; Ralff, Marie D; Zloza, Andrew; Chesson, Charles B; Newman, Jenna H; Kaufman, Howard; Bertino, Joseph; Stein, Mark; El-Deiry, Wafik S

    2018-06-01

    ONC201 is a first-in-class, orally active antitumor agent that upregulates cytotoxic TRAIL pathway signaling in cancer cells. ONC201 has demonstrated safety and preliminary efficacy in a first-in-human trial in which patients were dosed every 3 weeks. We hypothesized that dose intensification of ONC201 may impact antitumor efficacy. We discovered that ONC201 exerts dose- and schedule-dependent effects on tumor progression and cell death signaling in vivo. With dose intensification, we note a potent anti-metastasis effect and inhibition of cancer cell migration and invasion. Our preclinical results prompted a change in ONC201 dosing in all open clinical trials. We observed accumulation of activated NK+ and CD3+ cells within ONC201-treated tumors and that NK cell depletion inhibits ONC201 efficacy in vivo, including against TRAIL/ONC201-resistant Bax-/- tumors. Immunocompetent NCR1-GFP mice, in which NK cells express GFP, demonstrated GFP+ NK cell infiltration of syngeneic MC38 colorectal tumors. Activation of primary human NK cells and increased degranulation occurred in response to ONC201. Coculture experiments identified a role for TRAIL in human NK-mediated antitumor cytotoxicity. Preclinical results indicate the potential utility for ONC201 plus anti-PD-1 therapy. We observed an increase in activated TRAIL-secreting NK cells in the peripheral blood of patients after ONC201 treatment. The results offer what we believe to be a unique pathway of immune stimulation for cancer therapy.

  17. Permanent certification program for health information technology; revisions to ONC-Approved Accreditor processes. Final rule.

    Science.gov (United States)

    2011-11-25

    Under the authority granted to the National Coordinator for Health Information Technology by section 3001(c)(5) of the Public Health Service Act (PHSA) as added by the Health Information Technology for Economic and Clinical Health (HITECH) Act, this final rule establishes a process for addressing instances where the ONC-Approved Accreditor (ONC-AA) engages in improper conduct or does not perform its responsibilities under the permanent certification program. This rule also addresses the status of ONC-Authorized Certification Bodies (ONC-ACBs) in instances where there may be a change in the accreditation organization serving as the ONC-AA and clarifies the responsibilities of the new ONC-AA.

  18. Daily transactional and transformational leadership and daily employee engament

    NARCIS (Netherlands)

    Breevaart, K.; Bakker, A.B.; Hetland, Jorn; Demerouti, E.; Olsen, O.K.; Espevik, R.

    2014-01-01

    This diary study adds to the leadership literature by examining the daily influence of transformational leadership, contingent reward, and active management-by-exception (MBE active) on followers' daily work engagement. We compare the unique contribution of these leadership behaviours and focus on

  19. Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D3.

    Science.gov (United States)

    Takács, István; Tóth, Béla E; Szekeres, László; Szabó, Boglárka; Bakos, Bence; Lakatos, Péter

    2017-01-01

    The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D 3 -not previously investigated-will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D 3 . The present study is a controlled, randomized, open-label, multicenter clinical trial, 3  months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D 3 did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D 3 provide equal efficacy and safety profiles.

  20. Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway.

    Science.gov (United States)

    Huetson, Pernilla; Palmer, James L; Levorsen, Andrée; Fournier, Marie; Germe, Maeva; McLeod, Euan

    2015-01-01

    Lixisenatide is a potent, selective and short-acting once daily prandial glucagon-like peptide-1 receptor agonist which lowers glycohemoglobin and body weight by clinically significant amounts in patients with type 2 diabetes treated with basal insulin, with limited risk of hypoglycemia. To assess the cost-effectiveness of lixisenatide versus bolus insulin, both in combination with basal insulin, in patients with type 2 diabetes in Norway. The IMS CORE Diabetes Model, a non-product-specific and validated simulation model, was used to make clinical and cost projections. Transition probabilities, risk adjustments and the progression of complication risk factors were derived from the UK Prospective Diabetes Study, supplemented with Norwegian data. Patients were assumed to receive combination treatment with basal insulin, lixisenatide or bolus insulin therapy for 3 years, followed by intensification of a basal-bolus insulin regimen for their remaining lifetime. Simulated healthcare costs, taken from the public payer perspective, were derived from microcosting and diagnosis related groups, discounted at 4% per annum and reported in Norwegian krone (NOK). Productivity costs were also captured based on extractions from the Norwegian Labor and Welfare Administration. Health state utilities were derived from a systematic literature review. Sensitivity and scenario analyses were performed. Lixisenatide in combination with basal insulin was associated with increased quality-adjusted life years (QALYs) and reduced lifetime healthcare costs compared to bolus insulin in combination with basal insulin in patients with Type 2 diabetes, and can be considered dominant. The net monetary benefit of lixisenatide versus bolus insulin was NOK 39,369 per patient. Results were sensitive to discounting, the application of excess body weight associated disutility and uncertainty surrounding the changes in HbA1c. Lixisenatide may be considered an economically efficient therapy in combination

  1. 45 CFR 170.435 - ONC-ATCB application reconsideration.

    Science.gov (United States)

    2010-10-01

    ... Section 170.435 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH INFORMATION TECHNOLOGY HEALTH INFORMATION TECHNOLOGY STANDARDS, IMPLEMENTATION SPECIFICATIONS, AND CERTIFICATION CRITERIA AND CERTIFICATION PROGRAMS FOR HEALTH INFORMATION TECHNOLOGY Temporary Certification Program for HIT § 170.435 ONC...

  2. Comparison of Mometasone Furoate Monohydrate (Nasonex and Fluticasone Propionate (Flixonase Nasal Sprays in the Treatment of Dust Mite-sensitive Children with Perennial Allergic Rhinitis

    Directory of Open Access Journals (Sweden)

    Ka-Kit Mak

    2013-08-01

    Conclusion: Following the 4-week therapy, MFM provided greater improvement compared to FP for symptoms of childhood perennial-allergic rhinitis. Based on their TSSs, the MFM group experienced more effective relief of nasal symptoms, whereas the FP group experienced more effective relief of non-nasal symptoms.

  3. Tracking the daily availability of burn beds for national emergencies.

    Science.gov (United States)

    Barillo, David J; Jordan, Marion H; Jocz, Richard J; Nye, Donna; Cancio, Leopoldo C; Holcomb, John B

    2005-01-01

    Medical planning for Operation Iraqi Freedom included predictive models of expected number of burn casualties. In all but the best-case scenario, casualty estimates exceeded the capacity of the only Department of Defense burn center. Examination of existing federal-civilian disaster plans for military hospital augmentation revealed that bed availability data were neither timely nor accurate. Recognizing the need for accurate knowledge of burn bed availability, the Department of Defense requested assistance from the American Burn Association (ABA). Directors of burn centers in the United States were queried for interest in participation in a mass casualty plan to provide overflow burn bed capacity. A list of 70 participating burn centers was devised based upon proximity to planned military embarkation points. A computer tracking program was developed. Daily automated e-mail messages requesting bed status were sent to burn center directors at 6 am Central time with responses requested before 11 am. The collated list of national overflow burn bed capacity was e-mailed each day to the ABA Central Office and to federal and military agencies involved with burn patient triage and transportation. Once automated, this task required only 1-2 hours a day. Available burn-bed lists were generated daily between March 17 and May 2, 2003 and then every other day until May 9, 2003. A total of 2151 responses were received (mean, 43 burn centers per day). A system to track daily nationwide burn bed availability was successfully implemented. Although intended for military conflict, this system is equally applicable to civilian mass casualty situations. We advocate adoption of this or a similar bed tracking system by the ABA for use during burn mass casualty incidents.

  4. Chronic daily headaches

    Directory of Open Access Journals (Sweden)

    Fayyaz Ahmed

    2012-01-01

    Full Text Available Chronic Daily Headache is a descriptive term that includes disorders with headaches on more days than not and affects 4% of the general population. The condition has a debilitating effect on individuals and society through direct cost to healthcare and indirectly to the economy in general. To successfully manage chronic daily headache syndromes it is important to exclude secondary causes with comprehensive history and relevant investigations; identify risk factors that predict its development and recognise its sub-types to appropriately manage the condition. Chronic migraine, chronic tension-type headache, new daily persistent headache and medication overuse headache accounts for the vast majority of chronic daily headaches. The scope of this article is to review the primary headache disorders. Secondary headaches are not discussed except medication overuse headache that often accompanies primary headache disorders. The article critically reviews the literature on the current understanding of daily headache disorders focusing in particular on recent developments in the treatment of frequent headaches.

  5. Safety and Effectiveness of Once-Daily Tadalafil (5 mg) Therapy in Korean Men with Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms in a Real-World Clinical Setting: Results from a Post-Marketing Surveillance Study.

    Science.gov (United States)

    Won, Ji Eon; Chu, Ji Yeon; Choi, Hyunah Caroline; Chen, Yun; Park, Hyun Jun; Dueñas, Héctor José

    2018-05-01

    The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once daily (quaque die [everyday], QD) among Korean men with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in a real-world clinical setting. This was a single-country, prospective, observational cohort study in which patients newly prescribed tadalafil 5 mg QD for the treatment of BPH/LUTS were followed-up for 12±2 or 24±2 weeks, or to the last treatment, during post-marketing surveillance. Safety was evaluated in terms of the frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Effectiveness was assessed by changes in the International Prostate Symptom Score (IPSS) from baseline to each endpoint. All patients receiving ≥1 dose of tadalafil 5 mg QD (N=637) were included in the safety population. Two percent of patients (n=13) experienced 15 TEAEs of mild (n=10; 66.7%) or moderate (n=5; 33.3%) severity. No severe TEAEs and no SAEs were reported. Effectiveness evaluations included all patients receiving tadalafil who had both baseline and endpoint observations (12-week, N=265; 24-week, N=44). Compared with baseline, the mean IPSS total score (±standard error) significantly improved by 4.7±0.3 and 6.4±0.7 points at the 12- and 24-week endpoints, respectively (peffective in Korean men with BPH/LUTS in a real-world clinical setting. Copyright © 2018 Korean Society for Sexual Medicine and Andrology.

  6. Comparison of Provider-Assessed and Patient-Reported Outcome Measures of Acute Skin Toxicity During a Phase III Trial of Mometasone Cream Versus Placebo During Breast Radiotherapy: The North Central Cancer Treatment Group (N06C4)

    International Nuclear Information System (INIS)

    Neben-Wittich, Michelle A.; Atherton, Pamela J.; Schwartz, David J.; Sloan, Jeff A.; Griffin, Patricia C.; Deming, Richard L.; Anders, Jon C.; Loprinzi, Charles L.; Burger, Kelli N.; Martenson, James A.; Miller, Robert C.

    2011-01-01

    Purpose: Considerable interobserver variability exists among providers and between providers and patients when measuring subjective symptoms. In the recently published Phase III N06C4 trial of mometasone cream vs. placebo to prevent radiation dermatitis, the primary provider-assessed (PA) endpoint, using the Common Toxicity Criteria for Adverse Events (CTCAE), was negative. However, prospectively planned secondary analyses of patient-reported outcomes (PROs), using the Skindex-16 and Skin Toxicity Assessment Tool (STAT), were positive. This study assesses the relationship between PA outcomes and PROs. Methods and Materials: Pearson correlation coefficients were calculated to compare the three tools. Statistical correlations were defined as follows: 0.7, strong. Results: CTCAE dermatitis moderately correlated with STAT erythema, and CTCAE pruritus strongly correlated with STAT itching. CTCAE pruritus had a moderate correlation with Skindex-16 itching. Comparing the 2 PRO tools, Skindex-16 itching correlated moderately with STAT itching. Skindex-16 burning, hurting, irritation, and persistence all showed the strongest correlation with STAT burning; they showed moderate correlations with STAT itching and tenderness. Conclusions: The PRO Skindex-16 correlated well with the PRO portions of STAT, but neither tool correlated well with CTCAE. PROs delineated a wider spectrum of toxicity than PA measures and provided more information on rash, redness, pruritus, and annoyance measures compared with CTCAE findings of rash and pruritus. PROs may provide a more complete measure of patient experience than single-symptom, PA endpoints in clinical trials assessing radiation skin toxicity.

  7. Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study.

    Science.gov (United States)

    Feng, Yuan; Zhou, Jihong; Li, Zhanhua; Jiang, Ying; Zhou, Ying

    2016-01-01

    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines) and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5) induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID) mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.

  8. Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study.

    Directory of Open Access Journals (Sweden)

    Yuan Feng

    Full Text Available Tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5 induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.

  9. Daily Weather Records

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — These daily weather records were compiled from a subset of stations in the Global Historical Climatological Network (GHCN)-Daily dataset. A weather record is...

  10. Efficacy and safety of ciclesonide once daily and fluticasone propionate twice daily in children with asthma

    DEFF Research Database (Denmark)

    Pedersen, Søren; Engelstätter, Renate; Weber, Hans-Jochen

    2009-01-01

    BACKGROUND: Ciclesonide is a new inhaled corticosteroid (ICS). Information about its clinical efficacy and safety in relation to other ICS in children is needed for clinical positioning. OBJECTIVE: This 12-week, randomized, double-blind, double-dummy, three-arm, parallel-group study compared the ...

  11. Impact of continuous in-home rehabilitation on quality of life and activities of daily living in elderly clients over 1 year.

    Science.gov (United States)

    Imanishi, Miyuki; Tomohisa, Hisao; Higaki, Kazuo

    2017-11-01

    To verify the effect of in-home rehabilitation on quality of life and activities of daily living in elderly clients. In this non-randomized controlled intervention trial, elderly participants were separated into a rehabilitation or a non-rehabilitation group (n = 100 each). The non-rehabilitation group received basic in-home nursing care, including assistance with cooking, cleaning, toileting, meals and medication. The rehabilitation group received a physical treatment program provided by a licensed professional once a week and basic nursing care in the home. For each group, quality of life and activities of daily living were assessed approximately every 3 months over a 1-year period. Quality of life was evaluated using the Philadelphia Geriatric Center Morale Scale, and activities of daily living were evaluated based on the Functional Independence Measure. The rehabilitation group showed statistically significant improvements in both quality of life and activities of daily living. In contrast, the non-rehabilitation group, although showing slight improvement in quality of life at 9 months, showed almost no effects at the other time-points and no significant changes in activities of daily living over the course of the study. The results of the present study suggest that long-term continuous in-home rehabilitation might improve quality of life and activities of daily living in elderly clients. Geriatr Gerontol Int 2017; 17: 1866-1872. © 2017 Japan Geriatrics Society.

  12. Self-critical perfectionism, daily stress, and disclosure of daily emotional events.

    Science.gov (United States)

    Richardson, Clarissa M E; Rice, Kenneth G

    2015-10-01

    Although disclosure of stressful events can alleviate distress, self-critical perfectionism may pose an especially strong impediment to disclosure during stress, likely contributing to poorer psychological well-being. In the current study, after completing a measure of self-critical perfectionism (the Discrepancy subscale of the Almost Perfect Scale--Revised; Slaney, Rice, Mobley, Trippi, & Ashby, 2001), 396 undergraduates completed measures of stress and disclosure at the end of each day for 1 week. Consistent with hypotheses and previous research, multilevel modeling results indicated significant intraindividual coupling of daily stress and daily disclosure where disclosure was more likely when experiencing high stress than low stress. As hypothesized, Discrepancy moderated the relationship between daily stress and daily disclosure. Individuals higher in self-critical perfectionism (Discrepancy) were less likely to engage in disclosure under high stress, when disclosure is often most beneficial, than those with lower Discrepancy scores. These results have implications for understanding the role of stress and coping in the daily lives of self-critical perfectionists. (c) 2015 APA, all rights reserved).

  13. ONC201 induces cell death in pediatric non-Hodgkin's lymphoma cells

    OpenAIRE

    Talekar, Mala K; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S

    2015-01-01

    ONC201/TIC10 is a small molecule initially discovered by its ability to coordinately induce and activate the TRAIL pathway selectively in tumor cells and has recently entered clinical trials in adult advanced cancers. The anti-tumor activity of ONC201 has previously been demonstrated in several preclinical models of cancer, including refractory solid tumors and a transgenic lymphoma mouse model. Based on the need for new safe and effective therapies in pediatric non-Hodgkin's lymphoma (NHL) a...

  14. Treatment patterns in patients with type 2 diabetes mellitus treated with glucagon-like peptide-1 receptor agonists: Higher adherence and persistence with dulaglutide compared with once-weekly exenatide and liraglutide.

    Science.gov (United States)

    Alatorre, Carlos; Fernández Landó, Laura; Yu, Maria; Brown, Katelyn; Montejano, Leslie; Juneau, Paul; Mody, Reema; Swindle, Ralph

    2017-07-01

    To compare adherence (proportion of days covered [PDC]), persistence, and treatment patterns among patients with type 2 diabetes mellitus (T2DM) newly initiating glucagon-like peptide-1 receptor agonists (GLP-1RAs). More specifically, the main objectives were to compare dulaglutide vs exenatide once weekly and dulaglutide vs liraglutide. Patients with T2DM newly initiating dulaglutide, albiglutide, exenatide once weekly, exenatide twice daily and liraglutide between November 2014 and April 2015 were hierarchically selected from Truven Health's MarketScan Research Databases. Propensity score matching was used to account for selection bias. Adherence to and persistence with the index GLP-1RA, and switching and augmentation patterns were assessed during the 6-month post-index period. Mean adherence for the matched cohorts was significantly higher for dulaglutide than for exenatide once weekly (0.72 vs 0.61; P  < .0001) and liraglutide (0.71 vs 0.67; P  < .0001). The percentage of patients achieving PDC ≥ 0.80 was significantly higher for dulaglutide compared with exenatide once weekly (54.2% vs 37.9%; P  < .0001) and liraglutide (53.5% vs 44.3%; P  < .0001). The mean (standard deviation) days on treatment for all matched patients was significantly higher for patients in the dulaglutide cohort compared with those in the exenatide once-weekly (148.4 [55.4] vs 123.6 [61.6]; P  < .0001) and liraglutide cohorts (146.0 [56.9] vs 137.4 [60.1]; P  < .0001). A significantly lower proportion of patients on dulaglutide discontinued treatment compared with those on exenatide once weekly (26.2% vs 48.4%; P  < .0001) and those on liraglutide (28.0% vs 35.6%; P  < .0001). Dulaglutide initiators had significantly higher adherence, were more persistent, and had lower discontinuation rates compared with initiators of exenatide once weekly or liraglutide during the 6-month follow-up period. © 2017 Eli Lilly and Company. Diabetes, Obesity and

  15. Once-through hybrid sulfur process for nuclear hydrogen production

    International Nuclear Information System (INIS)

    Jeong, Y. H.

    2008-01-01

    Increasing concern about the global climate change spurs the development of low- or zero-carbon energy system. Nuclear hydrogen production by water electrolysis would be the one of the short-term solutions, but low efficiency and high production cost (high energy consumption) is the technical hurdle to be removed. In this paper the once-through sulfur process composed of the desulfurization and the water electrolysis systems is proposed. Electrode potential for the conventional water electrolysis (∼2.0 V) can be reduced significantly by the anode depolarization using sulfur dioxide: down to 0.6 V depending on the current density This depolarized electrolysis is the electrolysis step of the hybrid sulfur process originally proposed by the Westinghouse. However; recycling of sulfur dioxide requires a high temperature heat source and thus put another technical hurdle on the way to nuclear hydrogen production: the development of high temperature nuclear reactors and corresponding sulfuric acid decomposition system. By the once-through use of sulfur dioxide rather than the closed recycle, the hurdle can be removed. For the sulfur feed, the desulfurization system is integrated into the water electrolysis system. Fossil fuels include a few percent of sulfur by weight. During the refinement or energy conversion, most of the sulfur should be separated The separated sulfur can be fed to the water electrolysis system and the final product would be hydrogen and sulfuric acid, which is number one chemical in the world by volume. Lowered electrode potential and additional byproduct, the sulfuric acid, can provide economically affordable hydrogen. In this study, the once-through hybrid sulfur process for hydrogen production was proposed and the process was optimized considering energy consumption in electrolysis and sulfuric acid concentration. Economic feasibility of the proposed process was also discussed. Based on currently available experimental data for the electrode

  16. Concentrations of Dapivirine in the Rhesus Macaque and Rabbit following Once Daily Intravaginal Administration of a Gel Formulation of [14C]Dapivirine for 7 Days▿

    OpenAIRE

    Nuttall, Jeremy P.; Thake, Daryl C.; Lewis, Mark G.; Ferkany, John W.; Romano, Joseph W.; Mitchnick, Mark A.

    2007-01-01

    Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivir...

  17. Relationships Among Nightly Sleep Quality, Daily Stress, and Daily Affect.

    Science.gov (United States)

    Blaxton, Jessica M; Bergeman, Cindy S; Whitehead, Brenda R; Braun, Marcia E; Payne, Jessic D

    2017-05-01

    We explored the prospective, microlevel relationship between nightly sleep quality (SQ) and the subsequent day's stress on positive (PA) and negative affect (NA) as well as the moderating relationships between nightly SQ, subsequent stress, and subsequent PA on NA. We investigated whether age moderated these relationships. We collected 56 days of sleep, stress, and affect data using daily diary questionnaires (N = 552). We used multilevel modeling to assess relationships at the between- and within-person levels. Daily increases in SQ and decreases in stress interacted to predict higher daily PA and lower daily NA. Better SQ in older adults enhanced the benefits of PA on the stress-NA relationship more during times of low stress, whereas better sleep in younger adults enhanced the benefits of PA more during times of high stress. Between-person effects were stronger predictors of well-being outcomes than within-person variability. The combination of good SQ and higher PA buffered the impact of stress on NA. The moderating impact of age suggests that sleep and stress play different roles across adulthood. Targeting intervention and prevention strategies to improve SQ and enhance PA could disrupt the detrimental relationship between daily stress and NA. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. A clinical trial to evaluate the effects of flumethrin or ivermectin treatment on hemoparasites, gastrointestinal parasites, conception and daily weight gain in a dairy farm in Japan.

    Science.gov (United States)

    Yamane, I; Arai, S; Nakamura, Y; Hisashi, M; Fukazawa, Y; Onuki, T

    2000-02-01

    A clinical trial was performed to compare the effects of flumethrin and ivermectin treatments of grazing heifers at one farm in central Japan. 64 heifers were randomly allocated into two groups. Flumethrin (1 mg/kg pour on) was applied approximately once every 3 weeks to heifers in one group and heifers in the second group were injected approximately once every month with ivermectin (200 microg/kg; id). Between groups, no significant differences were detected in the proportions of animals that showed parasitemia of Theileria sergenti and conception risks. Significantly lower average log-transformed nematode-egg counts and higher average daily weight gain were observed in the ivermectin-treated group. Animals with higher body weight at the start of grazing and lower log-transformed total nematode-egg and coccidia-oocyst counts had higher odds of conceiving. Animals with ivermectin treatment, lower body weight at the start of grazing and lower log-transformed coccidia-oocyst count had higher daily weight gain. Ivermectin may be more useful in this farm because of the higher productivity for cattle and lower cost for its usage.

  19. Traversing every edge in each direction once, but not at once: Cubic (polyhedral graphs

    Directory of Open Access Journals (Sweden)

    Vladimir R. Rosenfeld

    2017-04-01

    Full Text Available A {\\em retracting-free bidirectional circuit} in a graph $G$ is a closed walk which traverses every edge exactly once in each direction and such that no edge is succeeded by the same edge in the opposite direction. Such a circuit revisits each vertex only in a number of steps. Studying the class $\\mathit{\\Omega}$ of all graphs admitting at least one retracting-free bidirectional circuit was proposed by Ore (1951 and is by now of practical use to nanotechnology. The latter needs in various molecular polyhedra that are constructed from a single chain molecule in the retracting-free way. Some earlier results for simple graphs, obtained by Thomassen and, then, by other authors, are specially refined by us for a cubic graph $Q$. Most of such refinements depend only on the number $n$ of vertices of $Q$.

  20. Technical architecture of ONC-approved plans for statewide health information exchange.

    Science.gov (United States)

    Barrows, Randolph C; Ezzard, John

    2011-01-01

    ONC-approved state plans for HIE were reviewed for descriptions and depictions of statewide HIE technical architecture. Review was complicated by non-standard organizational elements and technical terminology across state plans. Findings were mapped to industry standard, referenced, and defined HIE architecture descriptions and characteristics. Results are preliminary due to the initial subset of ONC-approved plans available, the rapid pace of new ONC-plan approvals, and continuing advancements in standards and technology of HIE, etc. Review of 28 state plans shows virtually all include a direct messaging component, but for participating entities at state-specific levels of granularity (RHIO, enterprise, organization/provider). About ½ of reviewed plans describe a federated architecture, and ¼ of plans utilize a single-vendor "hybrid-federated" architecture. About 1/3 of states plan to leverage new federal and open exchange technologies (DIRECT, CONNECT, etc.). Only one plan describes a centralized architecture for statewide HIE, but others combine central and federated architectural approaches.

  1. Combining Radar and Daily Precipitation Data to Estimate Meaningful Sub-daily Precipitation Extremes

    Science.gov (United States)

    Pegram, G. G. S.; Bardossy, A.

    2016-12-01

    Short duration extreme rainfalls are important for design. The purpose of this presentation is not to improve the day by day estimation of precipitation, but to obtain reasonable statistics for the subdaily extremes at gauge locations. We are interested specifically in daily and sub-daily extreme values of precipitation at gauge locations. We do not employ the common procedure of using time series of control station to determine the missing data values in a target. We are interested in individual rare events, not sequences. The idea is to use radar to disaggregate daily totals to sub-daily amounts. In South Arica, an S-band radar operated relatively continuously at Bethlehem from 1998 to 2003, whose scan at 1.5 km above ground [CAPPI] overlapped a dense (10 km spacing) set of 45 pluviometers recording in the same 6-year period. Using this valuable set of data, we are only interested in rare extremes, therefore small to medium values of rainfall depth were neglected, leaving 12 days of ranked daily maxima in each set per year, whose sum typically comprised about 50% of each annual rainfall total. The method presented here uses radar for disaggregating daily gauge totals in subdaily intervals down to 15 minutes in order to extract the maxima of sub-hourly through to daily rainfall at each of 37 selected radar pixels [1 km square in plan] which contained one of the 45 pluviometers not masked out by the radar foot-print. The pluviometer data were aggregated to daily totals, to act as if they were daily read gauges; their only other task was to help in the cross-validation exercise. The extrema were obtained as quantiles by ordering the 12 daily maxima of each interval per year. The unusual and novel goal was not to obtain the reproduction of the precipitation matching in space and time, but to obtain frequency distributions of the gauge and radar extremes, by matching their ranks, which we found to be stable and meaningful in cross-validation tests. We provide and

  2. Sliding mode fuzzy control for a once-through stream generator

    International Nuclear Information System (INIS)

    Zhang Guifeng; Shi Xiaocheng; Sun Tieli; Xiong Jinkui; Zhang Hongguo

    2007-01-01

    A once-through steam generator is important equipment in nuclear power plant, so its control level is high. A Sliding Mode Fuzzy Controller inherits the robustness property of Sliding Mode Control and the interpolation property of Fuzzy Logic Control. The robustness property of variable structure system makes the control system insensitive for different burthen variety and different outside disturbance. Fuzzy control predigests the device of control system and alleviates the chattering which variable structure system causes. So the control system can be made more ideal. The paper describes the design method of Sliding Mode Fuzzy Controller without its system model for a once-through steam generator. And the simulation results show that satisfying control results can be got. (authors)

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  4. Utility of radius bone densitometry for the treatment of osteoporosis with once-weekly teriparatide therapy

    Directory of Open Access Journals (Sweden)

    Harumi Nakayama

    2018-03-01

    Full Text Available Objectives: As clinics that treat patients with osteoporosis do not usually have central dual-energy X-ray absorptiometry (DXA, bone density is often measured with radial DXA. However, no long-term evidence exists for radius bone density outcomes following treatment with once-weekly teriparatide in actual medical treatment. Methods: We evaluated changes in bone density at 6-, 12-, and 18-month intervals using radial DXA in patients treated with once-weekly teriparatide for more than 6 months. Results: A significant increase in bone mineral density (BMD was observed at the 1/3 and 1/10 radius sites 12 months after the initiation of once-weekly teriparatide. We also observed that the rate of change in BMD was greater at the distal 1/10 radius than at the 1/3 radius. Conclusions: Considering these points, the effect of once-weekly teriparatide therapy can be observed at the radius. In clinics that do not have central DXA, but instead have radial DXA, these findings can help to evaluate the effect of once-weekly teriparatide treatment on osteoporosis. Keywords: Once-weekly teriparatide, Osteoporosis, Radius, Dual-energy X-ray absorptiometry

  5. Associations among daily stressors and salivary cortisol: findings from the National Study of Daily Experiences.

    Science.gov (United States)

    Stawski, Robert S; Cichy, Kelly E; Piazza, Jennifer R; Almeida, David M

    2013-11-01

    While much research has focused on linking stressful experiences to emotional and biological reactions in laboratory settings, there is an emerging interest in extending these examinations to field studies of daily life. The current study examined day-to-day associations among naturally occurring daily stressors and salivary cortisol in a national sample of adults from the second wave of the National Study of Daily Experiences (NSDE). A sample of 1694 adults (age=57, range=33-84; 44% male) completed telephone interviews detailing their stressors and emotions on eight consecutive evenings. Participants also provided saliva samples upon waking, 30min post-waking, before lunch and before bed, on four consecutive interview days resulting in 5995 days of interview/cortisol data. Analyses revealed three main findings. First, cortisol AUC was significantly higher on stressor days compared to stressor-free days, particularly for arguments and overloads at home, suggesting that daily stressors are associated with increased cortisol output, but that not all daily stressors have such an influence. Second, individuals reporting a greater frequency of stressor days also exhibited a steeper diurnal cortisol slope. Finally, daily stressor-cortisol associations were unaltered after adjustment for daily negative affect and physical symptoms. Our discussion focuses on the influence of naturally occurring daily stressors on daily cortisol and the role of daily diary approaches for studying healthy cortisol responses to psychosocial stressors outside of traditional laboratory settings. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Associations among Daily Stressors and Salivary Cortisol: Findings from the National Study of Daily Experiences

    Science.gov (United States)

    Stawski, Robert S.; Cichy, Kelly E.; Piazza, Jennifer R.; Almeida, David M.

    2013-01-01

    While much research has focused on linking stressful experiences to emotional and biological reactions in laboratory settings, there is an emerging interest in extending these examinations to field studies of daily life. The current study examined day-to-day associations among naturally-occurring daily stressors and salivary cortisol in a national sample of adults from the second wave of the National Study of Daily Experiences (NSDE). A sample of 1,694 adults (Age=57, Range=33–84; 44% male) completed telephone interviews detailing their stressors and emotions on eight consecutive evenings. Participants also provided saliva samples upon waking, 30 minutes post-waking, before lunch and before bed, on four consecutive interview days resulting in 5,995 days of interview/cortisol data. Analyses revealed three main findings. First, cortisol AUC was significantly higher on stressor days compared to stressor-free days, particularly for arguments and overloads at home, suggesting that daily stressors are associated with increased cortisol output, but that not all daily stressors have such an influence. Second, individuals reporting a greater frequency of stressor days also exhibited a steeper diurnal cortisol slope. Finally, daily stressor-cortisol associations were unaltered after adjustment for daily negative affect and physical symptoms. Our discussion focuses on the influence of naturally-occurring daily stressors on daily cortisol and the role of daily diary approaches for studying healthy cortisol responses to psychosocial stressors outside of traditional laboratory settings. PMID:23856186

  7. Comparison of once a day rifaximin to twice a day dosage in the prevention of recurrence of hepatic encephalopathy in patients with chronic liver disease.

    Science.gov (United States)

    Khokhar, Nasir; Qureshi, Muhammad Omar; Ahmad, Shafiq; Ahmad, Aiza; Khan, Hamza Hassan; Shafqat, Farzana; Salih, Muhammad

    2015-09-01

    Rifaximin has been used for prevention of recurrence of hepatic encephalopathy in twice a day dosage. The drug is expensive and lower dising may be possible. To determine the efficacy of rifaximin once a day dose in the prevention of hepatic encephalopathy (HE) in patients with liver cirrhosis as compared with twice daily dose of rifaximin. This Randomized control trial was carried out at the Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan from November 2012 to February 2014. Patients with known chronic liver disease with at least one episode of HE in the past were randomized to group A (rifaximin 550 mg OD) and group B (rifaximin 550 mg BD), after fulfilling the inclusion criteria. Each patient was followed for 6 months for any episode of HE. Patients in each group were identified for any breakthrough episode of encephalopathy during this period. Data were analyzed using SPSS version 16. Chi-squared test and t-test were applied where required to determine the significant difference between the two groups. There were a total of 306 patients: 128 patients in Group A while 178 in group B. Majority of patients (75.81%) had hepatitis C virus with mean age of 52.30 ± 9.92, MELD score 13.58 ± 8.3, and 55.22% were in Child-Pugh B. Eighty-one patients had an episode of HE during the study period. There were 27 patients in group A and 54 patients in group B with breakthrough episode of HE (P = 0.088). This study suggests that there is no significant difference in rifaximin once a day or twice daily dose in preventing HE. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  8. Number of Streptococcus mutans and Lactobacillus in saliva versus the status of cigarette smoking, considering duration of smoking and number of cigarettes smoked daily.

    Science.gov (United States)

    Nakonieczna-Rudnicka, Marta; Bachanek, Teresa

    2017-09-21

    A large number of colonies of Streptococcus mutans (SM) and Lactobacillus (LB) cariogenic bacteria in the saliva show a high risk of dental caries development. Cotinine is a biomarker of exposure to the tobacco smoke. The aim of the study was assessment of the number of Streptococcus mutans and Lactobacillus in the saliva of non-smokers and smokers considering the duration of smoking and the number of cigarettes smoked daily. The number of SM and LB was analysed in relation to the frequency of oral health check-ups. The investigated group comprised 124 people aged 20-54. 58 (46.8%) reported cigarette smoking; 66 (53.2%) reported they had never smoked cigarettes and had never attempted to smoke. Cotinine concentration in the saliva was assayed using the Cotinine test (Calbiotech), and the number of SM and LB with the use of the CRT bacteria test (Ivoclar Vivadent, Liechtenstein). Statistical analysis was conducted using Chi2 and Mann-Whitney tests. Test values of pSM and LB and the status of smoking, the number of cigarettes smoked daily and duration of cigarette smoking. Smokers who reported having dental check-ups at least once a year significantly more frequently had a small number of LB stated in relation to people who had dental check-ups to control their oral health less frequently than once a year. The number of SM and LB in saliva does not depend on the smoking status, the number of cigarettes smoked daily and duration of smoking.

  9. 30 CFR 241.76 - Can MMS reduce my penalty once it is assessed?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Can MMS reduce my penalty once it is assessed? 241.76 Section 241.76 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR... Provisions § 241.76 Can MMS reduce my penalty once it is assessed? Under 30 U.S.C. 1719(g), the Director or...

  10. Digital simulation for nuclear once-through steam generators

    International Nuclear Information System (INIS)

    Chen, A.T.

    1976-01-01

    Mathematical models for calculating the dynamic response of the Oconee type once through steam generator (OTSG) and the integral economizer once through steam generator (IEOTSG) was developed and presented in this dissertation. Linear and nonlinear models of both steam generator types were formulated using the state variable, lumped parameter approach. Transient and frequency responses of system parameters were calculated for various perturbations from both the primary coolant side and the secondary side. Transients of key parameters, including primary outlet temperature, superheated steam outlet temperature, boiling length/subcooled length and steam pressure, were generated, compared and discussed for both steam generator types. Frequency responses of delta P/sub s//deltaT/sub pin/ of the linear OTSG model were validated by using the dynamic testing results obtained at the Oconee I nuclear power station. A sensitivity analysis in both the time and the frequency domains was performed. It was concluded that the mathematical and computer models developed in this dissertation for both the OTSG and the IEOTSG are suitable for overall plant performance evaluation and steam generator related component/system design analysis for nuclear plants using either type of steam generator

  11. Safety and Effectiveness of Once-Daily Tadalafil (5 mg Therapy in Korean Men with Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms in a Real-World Clinical Setting: Results from a Post- Marketing Surveillance Study

    Directory of Open Access Journals (Sweden)

    Ji Eon Won

    2018-05-01

    Full Text Available Purpose: The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once daily (quaque die [everyday], QD among Korean men with benign prostatic hyperplasia (BPH/lower urinary tract symptoms (LUTS in a real-world clinical setting. Materials and Methods: This was a single-country, prospective, observational cohort study in which patients newly prescribed tadalafil 5 mg QD for the treatment of BPH/LUTS were followed-up for 12±2 or 24±2 weeks, or to the last treatment, during post-marketing surveillance. Safety was evaluated in terms of the frequency of treatment-emergent adverse events (TEAEs and serious adverse events (SAEs. Effectiveness was assessed by changes in the International Prostate Symptom Score (IPSS from baseline to each endpoint. Results: All patients receiving ≥1 dose of tadalafil 5 mg QD (N=637 were included in the safety population. Two percent of patients (n=13 experienced 15 TEAEs of mild (n=10; 66.7% or moderate (n=5; 33.3% severity. No severe TEAEs and no SAEs were reported. Effectiveness evaluations included all patients receiving tadalafil who had both baseline and endpoint observations (12-week, N=265; 24-week, N=44. Compared with baseline, the mean IPSS total score (±standard error significantly improved by 4.7±0.3 and 6.4±0.7 points at the 12- and 24-week endpoints, respectively (p<0.0001, with significant improvements also observed on the storage, voiding, and quality of life subscores. In total, 69.1% of the patients had a clinically meaningful ≥3-point improvement in the IPSS total score. Conclusions: Tadalafil 5 mg QD was well tolerated and effective in Korean men with BPH/LUTS in a real-world clinical setting.

  12. 76 FR 31272 - Permanent Certification Program for Health Information Technology; Revisions to ONC-Approved...

    Science.gov (United States)

    2011-05-31

    ... Permanent Certification Program for Health Information Technology; Revisions to ONC-Approved Accreditor Processes AGENCY: Office of the National Coordinator for Health Information Technology (ONC), Department of... Coordinator for Health Information Technology (the National Coordinator) by section 3001(c)(5) of the Public...

  13. In adolescence a higher 'eveningness in energy intake' is associated with higher total daily energy intake.

    Science.gov (United States)

    Diederichs, Tanja; Perrar, Ines; Roßbach, Sarah; Alexy, Ute; Buyken, Anette E

    2018-05-26

    The present manuscript addressed two hypotheses: (i) As children age, energy intake is shifted from morning (energy intake energy intake >6pm) (ii) A higher 'eveningness in energy intake' (i.e. evening minus morning energy intake) is associated with a higher total daily energy intake. Data were analyzed from 262 DONALD cohort study participants, who had completed at least one 3-day weighed dietary record in the age groups 3/4, 5/6, 7/8, 9/10, 11/12, 13/14, 15/16 and 17/18 years (y). 'Eveningness in energy intake' was compared across age groups and related to total daily energy intake for each age group (multiple cross-sectional analyses). 'Eveningness' increased progressively from age group 3/4y to age group 17/18y. A median surplus of evening energy intake (i.e. when evening intake exceeded morning intake) was firstly observed for age group 11/12y. From age group 11/12y onwards, a higher 'eveningness' was associated with a higher total daily energy intake (all p energy intake between the highest and the lowest tertile of 'eveningness' was largest for age group 17/18y, amounting to an 11% higher intake among adolescents in the highest as compared to those in the lowest tertile. In conclusion, energy intake progressively shifts from morning to evening hours as children age. Once evening energy intake exceeds morning energy intake, a higher 'eveningness in energy intake' is associated with higher total daily energy intake. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Once-through thorium cycles in Candu reactors

    International Nuclear Information System (INIS)

    Milgram, M.S.

    1982-01-01

    In once-through thorium cycles pure thorium fuel bundles can be irradiated conjointly with uranium fuel bundles in a CANDU reactor with parameters judiciously chosen such that the overall fuel cycle cost is competitive with other possibilities - notably low-enriched uranium. Uranium 233 can be created and stockpiled for possible future use with no imperative that it be used unless future conditions warrant, and a stockpile can be begun independently of the state of reprocessing technology. The existence and general properties of these cycles are discussed

  15. Initial inflight calibration for Hayabusa2 optical navigation camera (ONC) for science observations of asteroid Ryugu

    Science.gov (United States)

    Suzuki, H.; Yamada, M.; Kouyama, T.; Tatsumi, E.; Kameda, S.; Honda, R.; Sawada, H.; Ogawa, N.; Morota, T.; Honda, C.; Sakatani, N.; Hayakawa, M.; Yokota, Y.; Yamamoto, Y.; Sugita, S.

    2018-01-01

    Hayabusa2, the first sample return mission to a C-type asteroid was launched by the Japan Aerospace Exploration Agency (JAXA) on December 3, 2014 and will arrive at the asteroid in the middle of 2018 to collect samples from its surface, which may contain both hydrated minerals and organics. The optical navigation camera (ONC) system on board the Hayabusa2 consists of three individual framing CCD cameras, ONC-T for a telescopic nadir view, ONC-W1 for a wide-angle nadir view, and ONC-W2 for a wide-angle slant view will be used to observe the surface of Ryugu. The cameras will be used to measure the global asteroid shape, local morphologies, and visible spectroscopic properties. Thus, image data obtained by ONC will provide essential information to select landing (sampling) sites on the asteroid. This study reports the results of initial inflight calibration based on observations of Earth, Mars, Moon, and stars to verify and characterize the optical performance of the ONC, such as flat-field sensitivity, spectral sensitivity, point-spread function (PSF), distortion, and stray light of ONC-T, and distortion for ONC-W1 and W2. We found some potential problems that may influence our science observations. This includes changes in sensitivity of flat fields for all bands from those that were measured in the pre-flight calibration and existence of a stray light that arises under certain conditions of spacecraft attitude with respect to the sun. The countermeasures for these problems were evaluated by using data obtained during initial in-flight calibration. The results of our inflight calibration indicate that the error of spectroscopic measurements around 0.7 μm using 0.55, 0.70, and 0.86 μm bands of the ONC-T can be lower than 0.7% after these countermeasures and pixel binning. This result suggests that our ONC-T would be able to detect typical strength (∼3%) of the serpentine absorption band often found on CM chondrites and low albedo asteroids with ≥ 4

  16. 76 FR 72636 - Permanent Certification Program for Health Information Technology; Revisions to ONC-Approved...

    Science.gov (United States)

    2011-11-25

    ... Permanent Certification Program for Health Information Technology; Revisions to ONC-Approved Accreditor Processes AGENCY: Office of the National Coordinator for Health Information Technology (ONC), Department of... Coordinator for Health Information Technology by section 3001(c)(5) of the Public Health Service Act (PHSA) as...

  17. Constrained control of a once-through boiler with recirculation

    DEFF Research Database (Denmark)

    Trangbæk, K

    2008-01-01

    There is an increasing need to operate power plants at low load for longer periods of time. When a once-through boiler operates at a sufficiently low load, recirculation is introduced, significantly altering the control structure. This paper illustrates the possibilities for using constrained con...

  18. Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study

    OpenAIRE

    Feng, Yuan; Zhou, Jihong; Li, Zhanhua; Jiang, Ying; Zhou, Ying

    2016-01-01

    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines) and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis act...

  19. Meteorological Reference Years of Daily Mean Temperature during the Sunlight Time; Anos Tipos de Temperaturas Medias Diarias durante las Horas de Sol

    Energy Technology Data Exchange (ETDEWEB)

    Marchante Jimenez, M.; Ramirez Santigosa, L.N.; Mora Lopez, L.; Sidrach de Cardona Ortin, M.

    2002-07-01

    In this work the characterization of the daily mean temperature during the sunlight time has been analyzed. An algorithm for the hourly series generation from extreme daily values has been applied to evaluate the daily mean temperature during the sunlight time. A generic algorithm has been enounced as a function of the sunrise time. This algorithm allows taking into account the fractions related to the sunrise and sunset hours. This methodology has been applied in data from 45 Spanish stations, uniformly distributed in the Iberian Peninsula. Data for a period of 14 years has been used in most of locations, and once the interest variable has been calculated, the meteorological reference year of the daily mean temperature during the sunlight time has been evaluated in each stations. The next step is the evaluation of the daily mean temperature during the sunlight time in any point into the zone of evaluation, not only in the measured stations. >From the result data in each measured station, an geographic information system has been used in order to calculate the interpolation, obtaining maps with a data each 5 km for each of the 365 days of the year. Then, this results can be superposed with the solar radiation evaluation obtaining the input data for the sizing of the photovoltaic grid connected system in any point of the Spanish geography. (Author) 8 refs.

  20. Design and evaluation of the ONC health information technology curriculum.

    Science.gov (United States)

    Mohan, Vishnu; Abbott, Patricia; Acteson, Shelby; Berner, Eta S; Devlin, Corkey; Hammond, William E; Kukafka, Rita; Hersh, William

    2014-01-01

    As part of the Heath Information Technology for Economic and Clinical Health (HITECH) Act, the Office of the National Coordinator for Health Information Technology (ONC) implemented its Workforce Development Program, which included initiatives to train health information technology (HIT) professionals in 12 workforce roles, half of them in community colleges. To achieve this, the ONC tasked five universities with established informatics programs with creating curricular materials that could be used by community colleges. The five universities created 20 components that were made available for downloading from the National Training and Dissemination Center (NTDC) website. This paper describes an evaluation of the curricular materials by its intended audience of educators. We measured the quantity of downloads from the NTDC site and administered a survey about the curricular materials to its registered users to determine use patterns and user characteristics. The survey was evaluated using mixed methods. Registered users downloaded nearly half a million units or components from the NTDC website. We surveyed these 9835 registered users. 1269 individuals completed all or part of the survey, of whom 339 identified themselves as educators (26.7% of all respondents). This paper addresses the survey responses of educators. Successful aspects of the curriculum included its breadth, convenience, hands-on and course planning capabilities. Several areas were identified for potential improvement. The ONC HIT curriculum met its goals for community college programs and will likely continue to be a valuable resource for the larger informatics community in the future.

  1. ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer cells

    OpenAIRE

    Yuan, Xun; Kho, Dhonghyo; Xu, Jing; Gajan, Ambikai; Wu, Kongming; Wu, Gen Sheng

    2017-01-01

    ONC201 was previously identified as a first-in-class antitumor agent and small-molecule inducer of the TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) gene that induces apoptosis in cancer cells. ONC201 has a safety profile and is currently in phase II clinical trials for the treatment of various malignancies. In the current study, we examine the effect of ONC201 on triple-negative breast cancer cells (TNBC), a subtype of breast cancer that is sensitive to TRAIL. We find that ...

  2. Modelling and verification of once-through subcritical heat recovery steam generator

    International Nuclear Information System (INIS)

    Lee, Chae Soo; Choi, Young Jun; Kim, Hyun Gee; Yang, Ok Chul; Chong Chae Hon

    2004-01-01

    The once-through heat recovery steam generator is ideally matched to very high temperature and pressure, well into the supercritical range. Moreover this type of boiler is structurally simpler than drum type boiler. In drum type boiler, each tube play a well-defined role: water preheating, vaporization, superheating. Empirical equations are available to predict the average heat transfer coefficient for each regime. For once-through heat recovery steam generator, this is no more the case and mathematical models have to be adapted to account for the disappearance of drum type economizer, boiler, superheater. General equations have to be used for each tube of boiler, and actual heat transfer condition in each tube has to be identified

  3. The Intelence aNd pRezista Once A Day Study (INROADS): a multicentre, single-arm, open-label study of etravirine and darunavir/ritonavir as dual therapy in HIV-1-infected early treatment-experienced subjects.

    Science.gov (United States)

    Ruane, P J; Brinson, C; Ramgopal, M; Ryan, R; Coate, B; Cho, M; Kakuda, T N; Anderson, D

    2015-05-01

    Following antiretroviral therapy failure, patients are often treated with a three-drug regimen that includes two nucleoside/tide reverse transcriptase inhibitors [N(t)RTIs]. An alternative two-drug nucleoside-sparing regimen may decrease the pill burden and drug toxicities associated with the use of N(t)RTIs. The Intelence aNd pRezista Once A Day Study (INROADS; NCT01199939) evaluated the nucleoside-sparing regimen of etravirine 400 mg with darunavir/ritonavir 800/100 mg once-daily in HIV-1-infected treatment-experienced subjects or treatment-naïve subjects with transmitted resistance. In this exploratory phase 2b, single-arm, open-label, multicentre, 48-week study, the primary endpoint was the proportion of subjects who achieved HIV-1 RNA treatment-experienced subjects or treatment-naïve subjects with transmitted resistance was virologically efficacious and well tolerated. © 2014 British HIV Association.

  4. Cannabis and alcohol use, affect and impulsivity in psychiatric out-patients' daily lives.

    Science.gov (United States)

    Trull, Timothy J; Wycoff, Andrea M; Lane, Sean P; Carpenter, Ryan W; Brown, Whitney C

    2016-11-01

    Cannabis and alcohol are the most commonly used (il)licit drugs world-wide. We compared the effects of cannabis and alcohol use on within-person changes in impulsivity, hostility and positive affect at the momentary and daily levels, as they occurred in daily life. Observational study involving ecological momentary assessments collected via electronic diaries six random times a day for 28 consecutive days. Out-patients' everyday life contexts in Columbia, MO, USA. Ninety-three adult psychiatric out-patients (85% female; mean = 30.9 years old) with borderline personality or depressive disorders, who reported using only cannabis (n = 3), only alcohol (n = 58) or both (n = 32) at least once during the study period. Real-time, standard self-report measures of impulsivity, hostility and positive affect, as impacted by momentary reports of cannabis and alcohol use. Cannabis use was associated with elevated feelings of impulsivity at the day level [b = 0.83, 95% confidence interval (CI) = 0.17-1.49] and increased hostility at the momentary (b = 0.07, 95% CI = 0.01-0.12) and person (b = 0.81, 95% CI = 0.15-1.47) level. Alcohol use was associated with elevated feelings of impulsivity at the momentary (b = 0.42, 95% CI = 0.13-0.71) and day levels (b = 0.82, 95% CI = 0.22-1.41) and increased positive affect at the momentary (b = 0.12, 95% CI = 0.06-0.18) and day (b = 0.33, 95% CI = 0.16-0.49) levels. Cannabis and alcohol use are associated with increases in impulsivity (both), hostility (cannabis) and positive affect (alcohol) in daily life, and these effects are part of separate processes that operate on different time-scales (i.e. momentary versus daily). © 2016 Society for the Study of Addiction.

  5. A Daily Diary Approach to the Examination of Chronic Stress, Daily Hassles and Safety Perceptions in Hospital Nursing.

    Science.gov (United States)

    Louch, Gemma; O'Hara, Jane; Gardner, Peter; O'Connor, Daryl B

    2017-12-01

    Stress is a significant concern for individuals and organisations. Few studies have explored stress, burnout and patient safety in hospital nursing on a daily basis at the individual level. This study aimed to examine the effects of chronic stress and daily hassles on safety perceptions, the effect of chronic stress on daily hassles experienced and chronic stress as a potential moderator. Utilising a daily diary design, 83 UK hospital nurses completed three end-of-shift diaries, yielding 324 person days. Hassles, safety perceptions and workplace cognitive failure were measured daily, and a baseline questionnaire included a measure of chronic stress. Hierarchical multivariate linear modelling was used to analyse the data. Higher chronic stress was associated with more daily hassles, poorer perceptions of safety and being less able to practise safely, but not more workplace cognitive failure. Reporting more daily hassles was associated with poorer perceptions of safety, being less able to practise safely and more workplace cognitive failure. Chronic stress did not moderate daily associations. The hassles reported illustrate the wide-ranging hassles nurses experienced. The findings demonstrate, in addition to chronic stress, the importance of daily hassles for nurses' perceptions of safety and the hassles experienced by hospital nurses on a daily basis. Nurses perceive chronic stress and daily hassles to contribute to their perceptions of safety. Measuring the number of daily hassles experienced could proactively highlight when patient safety threats may arise, and as a result, interventions could usefully focus on the management of daily hassles.

  6. 76 FR 53524 - Culturally Significant Objects Imported for Exhibition Determinations: “Once Upon Many Times...

    Science.gov (United States)

    2011-08-26

    ... DEPARTMENT OF STATE [Public Notice: 7568] Culturally Significant Objects Imported for Exhibition Determinations: ``Once Upon Many Times: Legends and Myths in Himalayan Art'' SUMMARY: Notice is hereby given of... included in the exhibition ``Once Upon Many Times: Legends and Myths in Himalayan Art,'' imported from...

  7. Depression Among Non-Daily Smokers Compared to Daily Smokers and Never-Smokers in the United States: An Emerging Problem.

    Science.gov (United States)

    Weinberger, Andrea H; Gbedemah, Misato; Wall, Melanie M; Hasin, Deborah S; Zvolensky, Michael J; Chaiton, Michael; Goodwin, Renee D

    2017-09-01

    Depression is strongly associated with daily smoking. Yet, little is known about the association between depression and non-daily smoking. The aim of this study was to investigate the prevalence of past-year depression and changes in past-year depression over time among non-daily smokers, compared to daily smokers and never-smokers, overall and stratified by age, gender, income, nicotine dependence, and cigarettes per day. Data were drawn from the National Household Survey on Drug Use (NSDUH), an annual cross-sectional study of persons aged 12 and over (total study population N = 496 805). The prevalence of past-year depression was examined annually among non-daily smokers, daily smokers, and never-smokers from 2005 to 2013 using linear trend analyses. Past-year depression was common among 10.10% of non-daily smokers, common among 10.78% of daily smokers, and 5.51% of never-smokers in 2013. The prevalence of depression increased from 2005 to 2013 among non-daily smokers (9.06% vs. 10.10%; p = .034) while there was no significant change in depression over time among daily smokers. Increases in depression among non-daily smokers occurred for both men and women and appear most pronounced youth, those smoking fewer cigarettes, and those without nicotine dependence. The prevalence of depression among non-daily smokers was equivalent to daily smokers and nearly twice that among nonsmokers. Depression appears to be increasing over time in non-daily smokers especially among youth, those who smoke less, and those without nicotine dependence. More work on the mental health of non-daily smokers is needed as this is an increasing and understudied group. This is the first study to investigate changes in the prevalence of depression among non-daily smokers compared to daily smokers and never-smokers over the past decade in a nationally representative sample of the United States. The results suggest an increase in depression among non-daily smokers over time that did not

  8. DailyMed

    Data.gov (United States)

    U.S. Department of Health & Human Services — DailyMed provides high quality information about marketed drugs. This information includes FDA labels (package inserts). This Web site provides health information...

  9. Conceptual design of once-through helical steam generator for SMART

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Wan; Kim, J. I.; Kim, J. H. [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-12-01

    Conceptual design of once-through helical steam generator for the integral reactor SMART is developed. The once-through helical steam generator requires quite different design concepts from the steam generators used in loop type commercial reactors. In this study the design requirements satisfying the operating conditions of the steam generator are derived, and the arrangements and the dimensions of the major parts are determined. By describing the design procedure, the cost of redesign and the costs of developments of similar new steam generators are minimized. The three dimensional models developed make it possible to preview the interferences of the steam generator components and to minimize the possibility of significant design changes in the next design stage by the preliminary strength analysis of the major parts. A methodology for evaluation of flow induced vibration of steam generator tubes has been developed and a preliminary flow induced vibration analysis has been performed. 24 refs., 54 figs., 9 tabs. (Author)

  10. DYNAM, Once Through Boiling Flow with Steam Superheat, Laplace Transformation

    International Nuclear Information System (INIS)

    Schlueter, G.; Efferding, L.E.

    1973-01-01

    1 - Description of problem or function: DYNAM performs a dynamic analysis of once-through boiling flow oscillations with steam superheat. The model describing the superheat regime (single- phase, variable density fluid) for subcritical pressure operation is also applicable to the study of once-through operation using supercritical pressure water. 2 - Method of solution: Linearized partial differential conservation equations are solved using Laplace transformation of the temporal terms and integration of the spatial variations. DYNAM is written in complex variable notation. 3 - Restrictions on the complexity of the problem - Maxima of: 30 intervals used to describe the power distribution in the non-boiling and boiling regions, 29 boiling nodes, 7 intervals and corresponding friction multipliers read in per case, 14 exit qualities read in per case, 40 superheat nodes, 10 coefficients read in for the phi 2 vs, x-polynomial fit, 48 frequencies at which open-loop frequency response is desired, 48 frequencies at which signal output is desired

  11. THE CHARACTER ANALYSIS OF GLEN HANSARD IN ONCE FILM

    Directory of Open Access Journals (Sweden)

    Nani Rosnani Thamrin

    2013-12-01

    Full Text Available This paper analyzed the characterization of talented actor named Glen Hansard in Once film. This study employed a descriptive qualitative research design based on theories of Rahardjo (1985, Robert (1965, and Card (1988. Primary data sources were whole Once scenes film directed by John Carney which had low-budgeting production with two stars, Glen Hansard and Irglova, while secondary data sources were collected from the articles related to this study. This research mainly investigated two aspects involved two character analyses of the main actor, Hansard. The first one was the construction of Hansard’s characters and the second one was the effect between his character and another actors’ character. The study showed that Hansard’s characters were constructed by five factors: from what the character did and said, what the other characters said about him, how the appearance and its milieu were, influencing one and another.The study also found that he had struggle, visionary, ambitious, introvert, sensitive, straightforward and curious characters, but more characters that showed strong characters of his were struggle, visionary and ambitious, because the scenes reflected them more.

  12. Single agent and synergistic combinatorial efficacy of first-in-class small molecule imipridone ONC201 in hematological malignancies.

    Science.gov (United States)

    Prabhu, Varun V; Talekar, Mala K; Lulla, Amriti R; Kline, C Leah B; Zhou, Lanlan; Hall, Junior; Van den Heuvel, A Pieter J; Dicker, David T; Babar, Jawad; Grupp, Stephan A; Garnett, Mathew J; McDermott, Ultan; Benes, Cyril H; Pu, Jeffrey J; Claxton, David F; Khan, Nadia; Oster, Wolfgang; Allen, Joshua E; El-Deiry, Wafik S

    2018-01-01

    ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples. ONC201 induced caspase-dependent apoptosis that involved activation of the integrated stress response (ATF4/CHOP) pathway, inhibition of Akt phosphorylation, Foxo3a activation, downregulation of cyclin D1, IAP and Bcl-2 family members. ONC201 synergistically reduced cell viability in combination with cytarabine and 5-azacytidine in AML cells. ONC201 combined with cytarabine in a Burkitt's lymphoma xenograft model induced tumor growth inhibition that was superior to either agent alone. ONC201 synergistically combined with bortezomib in MM, MCL and ALCL cells and with ixazomib or dexamethasone in MM cells. ONC201 combined with bortezomib in a Burkitt's lymphoma xenograft model reduced tumor cell density and improved CHOP induction compared to either agent alone. These results serve as a rationale for ONC201 single-agent trials in relapsed/refractory acute leukemia, non-Hodgkin's lymphoma, MM and combination trial with dexamethasone in MM, provide pharmacodynamic biomarkers and identify further synergistic combinatorial regimens that can be explored in the clinic.

  13. Neighbourhood Walkability and Daily Steps in Adults with Type 2 Diabetes.

    Science.gov (United States)

    Hajna, Samantha; Ross, Nancy A; Joseph, Lawrence; Harper, Sam; Dasgupta, Kaberi

    2016-01-01

    There is evidence that greater neighbourhood walkability (i.e., neighbourhoods with more amenities and well-connected streets) is associated with higher levels of total walking in Europe and in Asia, but it remains unclear if this association holds in the Canadian context and in chronic disease populations. We examined the relationships of different walkability measures to biosensor-assessed total walking (i.e., steps/day) in adults with type 2 diabetes living in Montreal (QC, Canada). Participants (60.5±10.4 years; 48.1% women) were recruited through McGill University-affiliated clinics (June 2006 to May 2008). Steps/day were assessed once per season for one year with pedometers. Neighbourhood walkability was evaluated through participant reports, in-field audits, Geographic Information Systems (GIS)-derived measures, and the Walk Score®. Relationships between walkability and daily steps were estimated using Bayesian longitudinal hierarchical linear regression models (n = 131). Participants who reported living in the most compared to the least walkable neighbourhoods completed 1345 more steps/day (95% Credible Interval: 718, 1976; Quartiles 4 versus 1). Those living in the most compared to the least walkable neighbourhoods (based on GIS-derived walkability) completed 606 more steps per day (95% CrI: 8, 1203). No statistically significant associations with steps were observed for audit-assessed walkability or the Walk Score®. Adults with type 2 diabetes who perceived their neighbourhoods as more walkable accumulated more daily steps. This suggests that knowledge of local neighborhood features that enhance walking is a meaningful predictor of higher levels of walking and an important component of neighbourhood walkability.

  14. SU-E-T-86: Comparison of Two Commercially Available Programs for the Evaluation of Delivered Daily Dose Using Cone Beam CT (CBCT)

    International Nuclear Information System (INIS)

    Tuohy, R; Bosse, C; Mavroidis, P; Shi, Z; Crownover, R; Papanikolaou, N; Stathakis, S

    2014-01-01

    Purpose: In this study, two commercially available programs were compared for the evaluation of delivered daily dose using cone beam CT (CBCT). Methods: Thirty (n=30) patients previously treated in our clinic (10 prostate, 10 SBRT lung and 10 abdomen) were used in this study. The patients' plans were optimized and calculated using the Pinnacle treatment planning system. The daily CBCT scans were imported into Velocity and RayStation along with the corresponding planning CTs, structure sets and 3D dose distributions for each patient. The organs at risk (OAR) were contoured on each CBCT by the prescribing physician and were included in the evaluation of the daily delivered dose. Each CBCT was registered to the planning CT, once with rigid registration and then again, separately, with deformable registration. After registering each CBCT, the dose distribution from the planning CT was overlaid and the dose volume histograms (DVH) for the OAR and the planning target volumes (PTV) were calculated. Results: For prostate patients, we observed daily volume changes for the OARs. The DVH analysis for those patients showed variation in the sparing of the OARs while PTV coverage remained virtually unchanged using both Velocity and RayStation systems. Similar results were observed for abdominal patients. In contrast, for SBRT lung patients, the DVH for the OARs and target were comparable to those from the initial treatment plan. Differences in organ volume and organ doses were also observed when comparing the daily fractions using deformable and rigid registrations. Conclusion: By using daily CBCT dose reconstruction, we proved PTV coverage for prostate and abdominal targets is adequate. However, there is significant dosimetric change for the OARs. For lung SBRT patients, the delivered daily dose for both PTV and OAR is comparable to the planned dose with no significant differences

  15. Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, Andreas Brønden; Christensen, Mikkel

    2013-01-01

    The glucagon-like peptide (GLP)-1 receptor agonist lixisenatide (Lyxumia(®)) was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of...... of lixisenatide seems to be in combination with basal insulin. A large multicenter study will determine the future potential of lixisenatide in preventing cardiovascular events and mortality, in patients with type 2 diabetes and recent acute coronary syndrome....

  16. Dynamic analysis of once-through and closed fuel cycle economics using Monte Carlo simulation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sungyeol, E-mail: csy@kaeri.re.kr; Lee, Hyo Jik, E-mail: hyojik@kaeri.re.kr; Ko, Won Il, E-mail: nwiko@kaeri.re.kr

    2014-10-01

    Highlights: • Dynamic behavior of system costs, both reactor and fuel cycle costs, is analyzed. • Relative economics of once-through and closed fuel cycles is explored. • Probabilistic approaches are adopted for levelized electricity generation costs. • Main cost drivers for cost gaps between once-through and closed cycles are identified. - Abstract: Although no consensus about the best approach to manage spent fuels has been achieved, economics is one of the major criteria for assessing and selecting acceptable management options. This study compares the reactor and fuel cycle costs of the closed system associated with sodium-cooled fast reactors and pyroprocessing versus the once-through system. We specifically investigated the fuel cycle transition cases of the Republic of Korea from 2013 to 2100. The results revealed that the closed system (34.00 mills/kWh as a mean value) could be more expensive than the once-through system (32.75 mills/kWh). In contrast, the once-through fuel cycle costs (8.31 mills/kWh), excluding reactor costs, were projected to be greater than the closed fuel cycle costs (7.77 mills/kWh) because of the increased costs of interim storage estimated by the Korean government and the limited contribution of backend fuel cycle components to the discounted costs. The capital cost of sodium-cooled fast reactor is the largest component contributing to the cost gap between the two systems. Among fuel cycle components, pyroprocessing has the largest uncertainty contribution to the cost gap. We also calculated the breakeven unit costs of SFR capital cost and PWR spent fuel pyroprocessing cost.

  17. Daily and Sub-daily Precipitation for the Former USSR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset is a compilation of in situ daily and hourly meteorological observations for the former USSR initially obtained within the framework of several joint...

  18. Synchronization to light and mealtime of daily rhythms of locomotor activity, plasma glucose and digestive enzymes in the Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Guerra-Santos, Bartira; López-Olmeda, José Fernando; de Mattos, Bruno Olivetti; Baião, Alice Borba; Pereira, Denise Soledade Peixoto; Sánchez-Vázquez, Francisco Javier; Cerqueira, Robson Bahia; Albinati, Ricardo Castelo Branco; Fortes-Silva, Rodrigo

    2017-02-01

    The light-dark cycle and feeding can be the most important factors acting as synchronizers of biological rhythms. In this research we aimed to evaluate synchronization to feeding schedule of daily rhythms of locomotor activity and digestive enzymes of tilapia. For that purpose, 120 tilapias (65.0±0.6g) were distributed in 12 tanks (10 fish per tank) and divided into two groups. One group was fed once a day at 11:00h (zeitgeber time, ZT6) (ML group) and the other group was fed at 23:00h (ZT18) (MD group). The fish were anesthetized to collect samples of blood, stomach and midgut at 4-hour intervals over a period of 24h. Fish fed at ML showed a diurnal locomotor activity (74% of the total daily activity occurring during the light phase) and synchronization to the feeding schedule, as this group showed anticipation to the feeding time. Fish fed at MD showed a disruption in the pattern of locomotor activity and became less diurnal (59%). Alkaline protease activity in the midgut showed daily rhythm with the achrophase at the beginning of the dark phase in both ML and MD groups. Acid protease and amylase did not show significant daily rhythms. Plasma glucose showed a daily rhythm with the achrophase shifted by 12h in the ML and MD groups. These results revealed that the feeding time and light cycle synchronize differently the daily rhythms of behavior, digestive physiology and plasma metabolites in the Nile tilapia, which indicate the plasticity of the circadian system and its synchronizers. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Heavy water reactors on the once-through uranium cycle

    International Nuclear Information System (INIS)

    1978-05-01

    This paper presents preliminary technical and economic data to INFCE on the once-through uranium fuel cycle for use in early comparisons of alternate nuclear systems. The denatured thorium fuel cycle is discussed in a companion paper. Information for this paper was developed under an ongoing program, and more complete reporting of the evaluation of the heavy water reactor and its fuel cycles is planned toward the end of the year

  20. HemOnc.org: A Collaborative Online Knowledge Platform for Oncology Professionals.

    Science.gov (United States)

    Warner, Jeremy L; Cowan, Andrew J; Hall, Aric C; Yang, Peter C

    2015-05-01

    Cancer care involves extensive knowledge about numerous chemotherapy drugs and chemotherapy regimens. This information is constantly evolving, and there has been no freely available, comprehensive, centralized repository of chemotherapy information to date. We created an online, freely accessible, ad-free, collaborative wiki of chemotherapy information entitled HemOnc.org to address the unmet need for a central repository of this information. This Web site was developed with wiki development software and is hosted on a cloud platform. Chemotherapy drug and regimen information (including regimen variants), as well as other information of interest to hematology/oncology professionals, is housed on the site in a fully referenced and standardized format. Accredited users are allowed to freely contribute information to the site. From its inception in November 2011, HemOnc.org has grown rapidly and most recently has detailed information on 383 drugs and 1,298 distinct chemotherapy regimens (not counting variants) in 92 disease subtypes. There are regularly more than 2,000 visitors per week from the United States and international locations. A user evaluation demonstrated that users find the site useful, usable, and recommendable. HemOnc.org is now the largest free source of chemotherapy drug and regimen information and is widely used. Future enhancements, including more metadata about drugs and increasingly detailed efficacy and toxicity information, will continue to improve the value of the resource. Copyright © 2015 by American Society of Clinical Oncology.

  1. Low Load Model of a Once-through Boiler with Recirculation

    DEFF Research Database (Denmark)

    Trangbæk, Klaus

    2006-01-01

    A dynamic simulation model of a once-through boiler in low to medium load is developed. When the system is in low load, water from the evaporator is recirculated through a bottle. This recirculation system is included in the model, which is then shown to fit closed-loop data from a real plant...

  2. The Combined Effects of Daily Stressors and Major Life Events on Daily Subjective Ages.

    Science.gov (United States)

    Bellingtier, Jennifer A; Neupert, Shevaun D; Kotter-Grühn, Dana

    2017-07-01

    Stressors may be a contributing factor in determining how old an individual feels, looks, or would like to be. Currently, little research has been devoted to understanding the relationship between stressors and subjective age in older adults. We focus on the combined impact of major life-event stressors and daily stressors on multiple indicators of subjective age: felt age, ideal age, and look age. Furthermore, we examine the process by which daily stressors relate to subjective ages by testing whether positive affect, control, and negative affect mediate this relationship. Using a daily-diary design, the current study measured older adults' (60-96 years old) stressors, subjective ages, personal control, and affect. Felt, ideal, and look ages each demonstrated a unique pattern of interactions between daily stressors and major life-event stressors. Furthermore, our findings suggest that on the daily level, the relationship between stressors and felt age is mediated by negative affect but not by control and positive affect. Findings indicate the need to consider the broader contextual picture of stressors, as well as their differential impact on multiple indicators of subjective age. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Skeletal muscle adaptation and performance responses to once a day versus twice every second day endurance training regimens.

    Science.gov (United States)

    Yeo, Wee Kian; Paton, Carl D; Garnham, Andrew P; Burke, Louise M; Carey, Andrew L; Hawley, John A

    2008-11-01

    We determined the effects of a cycle training program in which selected sessions were performed with low muscle glycogen content on training capacity and subsequent endurance performance, whole body substrate oxidation during submaximal exercise, and several mitochondrial enzymes and signaling proteins with putative roles in promoting training adaptation. Seven endurance-trained cyclists/triathletes trained daily (High) alternating between 100-min steady-state aerobic rides (AT) one day, followed by a high-intensity interval training session (HIT; 8 x 5 min at maximum self-selected effort) the next day. Another seven subjects trained twice every second day (Low), first undertaking AT, then 1-2 h later, the HIT. These training schedules were maintained for 3 wk. Forty-eight hours before and after the first and last training sessions, all subjects completed a 60-min steady-state ride (60SS) followed by a 60-min performance trial. Muscle biopsies were taken before and after 60SS, and rates of substrate oxidation were determined throughout this ride. Resting muscle glycogen concentration (412 +/- 51 vs. 577 +/- 34 micromol/g dry wt), rates of whole body fat oxidation during 60SS (1,261 +/- 247 vs. 1,698 +/- 174 micromol.kg(-1).60 min(-1)), the maximal activities of citrate synthase (45 +/- 2 vs. 54 +/- 1 mmol.kg dry wt(-1).min(-1)), and beta-hydroxyacyl-CoA-dehydrogenase (18 +/- 2 vs. 23 +/- 2 mmol.kg dry wt(-1).min(-1)) along with the total protein content of cytochrome c oxidase subunit IV were increased only in Low (all P every second day compromised high-intensity training capacity. While selected markers of training adaptation were enhanced with twice a day training, the performance of a 1-h time trial undertaken after a 60-min steady-state ride was similar after once daily or twice every second day training programs.

  4. Effect of once a week endurance exercise on fitness status in sedentary subjects.

    Science.gov (United States)

    Hiruntrakul, Ashira; Nanagara, Ratanavadee; Emasithi, Alongkot; Borer, Katarina T

    2010-09-01

    To study whether 3-months aerobic exercise training at moderate intensity once a week can increase fitness status in healthy sedentary young men. Randomized controlled study was performed in 37 sedentary young men, 18 to 25 years old. The exercise group (19) was assigned to work on bicycle ergometry at 60% of maximal effort, once a week for 12 weeks. The control group (18) lived a normal life style. Before and after training, aerobic fitness (VO2(max)), resting heart rate, lipid profile, and isokinetic power and strength of shoulder and knee were evaluated. In the exercise group, there was a significant increase in most fitness parameters compared with control, VO2(max) (19.7%), isokinetic power and strength of shoulder and knee (14.9%), and resting heart rate decreased (7.4%). Moderate-intensity training once a week for at least 12 weeks was sufficient to increase aerobic fitness in sedentary young men. This low frequency of exercise training may be used to encourage sedentary individuals for more compliance with physical activity.

  5. Modelling of Sub-daily Hydrological Processes Using Daily Time-Step Models: A Distribution Function Approach to Temporal Scaling

    Science.gov (United States)

    Kandel, D. D.; Western, A. W.; Grayson, R. B.

    2004-12-01

    Mismatches in scale between the fundamental processes, the model and supporting data are a major limitation in hydrologic modelling. Surface runoff generation via infiltration excess and the process of soil erosion are fundamentally short time-scale phenomena and their average behaviour is mostly determined by the short time-scale peak intensities of rainfall. Ideally, these processes should be simulated using time-steps of the order of minutes to appropriately resolve the effect of rainfall intensity variations. However, sub-daily data support is often inadequate and the processes are usually simulated by calibrating daily (or even coarser) time-step models. Generally process descriptions are not modified but rather effective parameter values are used to account for the effect of temporal lumping, assuming that the effect of the scale mismatch can be counterbalanced by tuning the parameter values at the model time-step of interest. Often this results in parameter values that are difficult to interpret physically. A similar approach is often taken spatially. This is problematic as these processes generally operate or interact non-linearly. This indicates a need for better techniques to simulate sub-daily processes using daily time-step models while still using widely available daily information. A new method applicable to many rainfall-runoff-erosion models is presented. The method is based on temporal scaling using statistical distributions of rainfall intensity to represent sub-daily intensity variations in a daily time-step model. This allows the effect of short time-scale nonlinear processes to be captured while modelling at a daily time-step, which is often attractive due to the wide availability of daily forcing data. The approach relies on characterising the rainfall intensity variation within a day using a cumulative distribution function (cdf). This cdf is then modified by various linear and nonlinear processes typically represented in hydrological and

  6. Feasibility assessment of the once-through thorium fuel cycle for the PTVM LWR concept

    International Nuclear Information System (INIS)

    Rachamin, R.; Fridman, E.; Galperin, A.

    2015-01-01

    Highlights: • The PTVM LWR is an innovation reactor concept operating in a “breed & burn” mode. • An advanced once-through thorium fuel cycle for the PTVM LWR concept is proposed. • The PTVM LWR concept makes use of a seed-blanket geometry. • A novel fuel management scheme based on two separate fuel flow routes is analyzed. • The analysis indicates a potential for utilizing the fuel in an efficient manner. - Abstract: This paper investigates the feasibility of a once-through thorium fuel cycle for the novel reactor-design concept named the pressure tube light water reactor with variable moderator control (PTVM LWR). The PTVM LWR operates in a “breed & burn” mode, which makes it an attractive system for utilizing thorium fuel in a once-through mode. The “breed & burn” mode can emphasize the in situ generation as well as incineration of 233 U, which are the basic foundations of the once-through thorium fuel cycle. The PTVM LWR concept makes use of a seed–blanket geometry, whereby the core is divided into separated regions of thorium-based fuel channel assemblies (blanket) and low-enriched uranium (LEU) based fuel channel assemblies (seed). A novel fuel in-core management scheme based on two separate fuel flow routes (i.e., seed route and blanket route) is proposed and analyzed. Neutronic performance analysis indicates that the proposed novel fuel in-core management scheme has the potential to utilize both LEU- and thorium-based fuel in an efficient manner. The once-through thorium cycle, presented and discussed in this paper, provide interesting research leads and can serve as a bridge between current LEU-based fuel cycles and a thorium fuel cycle based on recycling of 233 U

  7. Targeted ultraviolet B phototherapy in vitiligo: A comparison between once-weekly and twice-weekly treatment regimens

    Directory of Open Access Journals (Sweden)

    Imran Majid

    2015-01-01

    Full Text Available Background: Targeted ultraviolet B (T-UVB phototherapy in vitiligo is usually administered twice or thrice a week on non-consecutive days. It is difficult for many patients to adhere to this regimen, forcing them to discontinue treatment. Aim: The study aimed to compare the efficacy of twice-weekly and once-weekly targeted ultraviolet B phototherapy regimens in vitiligo. Methods: Sixty patients with non-segmental vitiligo on the face, neck or trunk were divided into two groups of 30 patients each. The patients in group A received targeted ultraviolet B twice weekly, while those in group B received targeted ultraviolet B once weekly. Repigmentation was monitored and graded as excellent (≥75% repigmentation, good (50−74% repigmentation and poor (<50% repigmentation. The extent of repigmentation at each body site (primary outcome measure, the number of doses required for initiation of pigmentation, and the cumulative dose of targeted ultraviolet B administered was calculated and compared between both groups. Results: A total of 90 lesions (48 in the twice weeklygroup and 42 in the once weekly group were treated on the face, neck and trunk. Excellent results were obtained in 62.5% (30/48 of lesions treated twice weekly, and 64.3% (27/42 in lesions treated once weekly. The mean number of doses required for initiation of pigmentation was 4.69 in the twice weekly group, and 4.35 in the once weekly group. The patients in the twice weekly group received a mean cumulative dose of 8.26 J/cm 2, while the once weekly group received 7.69 J/cm 2. No statistically significant differences were observed between the two groups with respect to the outcome, with respect to the total repigmentation, the number of doses till onset of pigmentation, as well as the cumulative dose of targeted UVB. Conclusion: Once-weekly targeted ultraviolet B phototherapy appears to be as efficacious as the twice-weekly regimen in vitiligo.

  8. DNA adenine methylation is required to replicate both Vibrio cholerae chromosomes once per cell cycle.

    Science.gov (United States)

    Demarre, Gaëlle; Chattoraj, Dhruba K

    2010-05-06

    DNA adenine methylation is widely used to control many DNA transactions, including replication. In Escherichia coli, methylation serves to silence newly synthesized (hemimethylated) sister origins. SeqA, a protein that binds to hemimethylated DNA, mediates the silencing, and this is necessary to restrict replication to once per cell cycle. The methylation, however, is not essential for replication initiation per se but appeared so when the origins (oriI and oriII) of the two Vibrio cholerae chromosomes were used to drive plasmid replication in E. coli. Here we show that, as in the case of E. coli, methylation is not essential for oriI when it drives chromosomal replication and is needed for once-per-cell-cycle replication in a SeqA-dependent fashion. We found that oriII also needs SeqA for once-per-cell-cycle replication and, additionally, full methylation for efficient initiator binding. The requirement for initiator binding might suffice to make methylation an essential function in V. cholerae. The structure of oriII suggests that it originated from a plasmid, but unlike plasmids, oriII makes use of methylation for once-per-cell-cycle replication, the norm for chromosomal but not plasmid replication.

  9. Table for monthly average daily extraterrestrial irradiation on horizontal surface and the maximum possible sunshine duration

    International Nuclear Information System (INIS)

    Jain, P.C.

    1984-01-01

    The monthly average daily values of the extraterrestrial irradiation on a horizontal surface (H 0 ) and the maximum possible sunshine duration are two important parameters that are frequently needed in various solar energy applications. These are generally calculated by scientists each time they are needed and by using the approximate short-cut methods. Computations for these values have been made once and for all for latitude values of 60 deg. N to 60 deg. S at intervals of 1 deg. and are presented in a convenient tabular form. Values of the maximum possible sunshine duration as recorded on a Campbell Stoke's sunshine recorder are also computed and presented. These tables should avoid the need for repetition and approximate calculations and serve as a useful ready reference for solar energy scientists and engineers. (author)

  10. Uranium savings on a once through PWR fuel cycle

    International Nuclear Information System (INIS)

    Cupo, J.V.

    1980-01-01

    A number of alternatives which have the greatest potential for near term savings with minimum plant and fuel modifications have been examined at Westinghouse as part of continued internal assessment and part of NASAP study conducted for DOE pertaining to uranium utilization in a once through PWR fuel cycle. The alternatives which could be retrofitted to existing reactors were examined in more detail in the evaluation since they would have the greater near term impact on U savings

  11. The once-through mode of steam generator reflux condensation in loss of coolant accident scenarios

    International Nuclear Information System (INIS)

    Liao, Y.; Guentay, S.; Suckow, D.

    2009-01-01

    The once-through mode of steam generator reflux condensation in the presence of noncondensable gases and/or aerosols for LOCA scenarios is introduced. This phenomenon is planned to be investigated at Paul Scherrer Institute in the ARTIST/RFLX experimental program. The plausible accident scenarios associated with the once-through reflux condensation are analyzed with MELCOR to study the safety significance and the boundary conditions of this phenomenon. This work presents the recent PSI experimental and analytical work on reflux condensation: the progress of modification to the ARTIST test facility for the purpose to study reflux condensation, and the analytical model for the once-through reflux condensation in the presence of noncondensable gas using the heat and mass transfer analogy approach. Future experimental and analytical work on reflux condensation is also outlined. (author)

  12. Rajeev Khedkar Impacts Once we had discussed the causes, we ...

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

    Kelly Haggart

    Once we had discussed the causes, we looked at some of the effects. Because of this lack of ownership of village land, what are the effects in your lives? So they ... lot of things will automatically change: schools, health care, drinking water – and it is possible that they will be able to come out of the cycle of bonded labour.

  13. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment.

    Science.gov (United States)

    Ranganath, Lakshminarayan R; Milan, Anna M; Hughes, Andrew T; Dutton, John J; Fitzgerald, Richard; Briggs, Michael C; Bygott, Helen; Psarelli, Eftychia E; Cox, Trevor F; Gallagher, James A; Jarvis, Jonathan C; van Kan, Christa; Hall, Anthony K; Laan, Dinny; Olsson, Birgitta; Szamosi, Johan; Rudebeck, Mattias; Kullenberg, Torbjörn; Cronlund, Arvid; Svensson, Lennart; Junestrand, Carin; Ayoob, Hana; Timmis, Oliver G; Sireau, Nicolas; Le Quan Sang, Kim-Hanh; Genovese, Federica; Braconi, Daniela; Santucci, Annalisa; Nemethova, Martina; Zatkova, Andrea; McCaffrey, Judith; Christensen, Peter; Ross, Gordon; Imrich, Richard; Rovensky, Jozef

    2016-02-01

    Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone. A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy. In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range. EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Daily Aspirin Therapy: Understand the Benefits and Risks

    Science.gov (United States)

    Daily aspirin therapy: Understand the benefits and risks Daily aspirin therapy can be a lifesaving option, but it's not ... everyone. Get the facts before considering a daily aspirin. By Mayo Clinic Staff Daily aspirin therapy may ...

  15. First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors.

    Science.gov (United States)

    Stein, Mark N; Bertino, Joseph R; Kaufman, Howard L; Mayer, Tina; Moss, Rebecca; Silk, Ann; Chan, Nancy; Malhotra, Jyoti; Rodriguez, Lorna; Aisner, Joseph; Aiken, Robert D; Haffty, Bruce G; DiPaola, Robert S; Saunders, Tracie; Zloza, Andrew; Damare, Sherri; Beckett, Yasmeen; Yu, Bangning; Najmi, Saltanat; Gabel, Christian; Dickerson, Siobhan; Zheng, Ling; El-Deiry, Wafik S; Allen, Joshua E; Stogniew, Martin; Oster, Wolfgang; Mehnert, Janice M

    2017-08-01

    Purpose: ONC201 is a small-molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, pharmacokinetic, and pharmacodynamic information. Results: No grade >1 drug-related adverse events occurred, and the RP2D was defined as 625 mg. Pharmacokinetic analysis revealed a C max of 1.5 to 7.5 μg/mL (∼3.9-19.4 μmol/L), mean half-life of 11.3 hours, and mean AUC of 37.7 h·μg/L. Pharmacodynamic assays demonstrated induction of caspase-cleaved keratin 18 and prolactin as serum biomarkers of apoptosis and DRD2 antagonism, respectively. No objective responses by RECIST were achieved; however, radiographic regression of several individual metastatic lesions was observed along with prolonged stable disease (>9 cycles) in prostate and endometrial cancer patients. Conclusions: ONC201 is a selective DRD2 antagonist that is well tolerated, achieves micromolar plasma concentrations, and is biologically active in advanced cancer patients when orally administered at 625 mg every 3 weeks. Clin Cancer Res; 23(15); 4163-9. ©2017 AACR . ©2017 American Association for Cancer Research.

  16. DNA adenine methylation is required to replicate both Vibrio cholerae chromosomes once per cell cycle.

    Directory of Open Access Journals (Sweden)

    Gaëlle Demarre

    2010-05-01

    Full Text Available DNA adenine methylation is widely used to control many DNA transactions, including replication. In Escherichia coli, methylation serves to silence newly synthesized (hemimethylated sister origins. SeqA, a protein that binds to hemimethylated DNA, mediates the silencing, and this is necessary to restrict replication to once per cell cycle. The methylation, however, is not essential for replication initiation per se but appeared so when the origins (oriI and oriII of the two Vibrio cholerae chromosomes were used to drive plasmid replication in E. coli. Here we show that, as in the case of E. coli, methylation is not essential for oriI when it drives chromosomal replication and is needed for once-per-cell-cycle replication in a SeqA-dependent fashion. We found that oriII also needs SeqA for once-per-cell-cycle replication and, additionally, full methylation for efficient initiator binding. The requirement for initiator binding might suffice to make methylation an essential function in V. cholerae. The structure of oriII suggests that it originated from a plasmid, but unlike plasmids, oriII makes use of methylation for once-per-cell-cycle replication, the norm for chromosomal but not plasmid replication.

  17. Outgoing Longwave Radiation Daily Climate Data Record (OLR Daily CDR)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The product contains the 1-degree by 1-degree daily mean outgoing longwave radiation flux at the top of the atmosphere derived from HIRS radiance observations...

  18. 7 CFR 1486.302 - Can changes be made to a project once it has been approved?

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Can changes be made to a project once it has been... MARKETS PROGRAM Program Operations § 1486.302 Can changes be made to a project once it has been approved? (a) Approved projects may be modified if circumstances change in such a way that they would likely...

  19. Logistiline Daily Service / Paavo Kangur

    Index Scriptorium Estoniae

    Kangur, Paavo, 1966-

    2005-01-01

    Sügisel ostis Leedu endise majandusministri Valetntinas Milaknise firma Daily Service ära kõik bürootarvetemüüja Reval Impexi aktsiad. 300 miljoni kroonise aastakäibega firma Eesti tütarettevõte prognoosib oma tänavuseks käibeks 31,2 miljonit krooni. Lisa: Daily Service'i struktuur

  20. Daily job demands and employee work engagement: The role of daily transformational leadership behavior.

    Science.gov (United States)

    Breevaart, Kimberley; Bakker, Arnold B

    2018-07-01

    Using job demands-resources (JD-R) theory, the present study integrates the challenge stressor-hindrance stressor framework and leadership theory to investigate the relationship between daily transformational leadership behavior and employee work engagement. We hypothesized that daily transformational leadership behavior (a) sustains employee work engagement on days characterized by high challenge job demands, and (b) protects work engagement on days characterized by high hindrance job demands. Teachers filled out a short online questionnaire at the end of each workday during a 2-week period (N = 271 × 5.68 days = 1539). Results of latent moderated structural equation modeling showed that teachers' daily challenge demands (workload and cognitive demands) had a positive relationship with work engagement on the days transformational leadership was high (vs. low). In addition, teachers' daily hindrance demands (role-conflict, but not family to work conflict) had a negative relationship with work engagement on the days transformational leadership was low (vs. high). These findings show that the function of transformational leadership behavior changes from day to day, and depends on the type of job demand. We discuss the practical and theoretical implications of these findings. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  1. Productive and counterproductive job crafting: A daily diary study.

    Science.gov (United States)

    Demerouti, Evangelia; Bakker, Arnold B; Halbesleben, Jonathon R B

    2015-10-01

    The present study aims to uncover the way daily job crafting influences daily job performance (i.e., task performance, altruism, and counterproductive work behavior). Job crafting was conceptualized as "seeking resources," "seeking challenges," and "reducing demands" and viewed as strategies individuals use to optimize their job characteristics. We hypothesized that daily job crafting relates to daily job demands and resources (work pressure and autonomy), which consequently relate to daily work engagement and exhaustion and ultimately to job performance. A sample of 95 employees filled in a quantitative diary for 5 consecutive working days (n occasions = 475). We predicted and found that daily seeking resources was positively associated with daily task performance because daily autonomy and work engagement increased. In contrast, daily reducing demands was detrimental for daily task performance and altruism, because employees lower their daily workload and consequently their engagement and exhaustion, respectively. Only daily seeking challenges was positively (rather than negatively) associated with daily counterproductive behavior. We conclude that employee job crafting can have both beneficial and detrimental effects on job performance. (c) 2015 APA, all rights reserved).

  2. Manufacture of Daily Check Device and Efficiency Evaluation for Daily Q.A

    International Nuclear Information System (INIS)

    Kim, Chan Yong; Jae, Young Wan; Park, Heung Deuk; Lee, Jae Hee

    2005-01-01

    Daily Q.A is the important step which must be preceded in a radiation treatment. Specially, radiation output measurement and laser alignment, SSD indicator related to a patient set-up recurrence must be confirmed for a reasonable radiation treatment. Daily Q.A proceeds correctness and a prompt way, and needs an objective measurement basis. Manufacture of the device which can facilitate confirmation of output measurement and appliances check at one time was requested. Produced the phantom formal daily check device which can confirm a lot of appliances check (output measurement and laser alignment. field size, SSD indicator) with one time of set up at a time, and measurement observed a linear accelerator (4 machine) for four months and evaluated efficiency. We were able to confirm an laser alignment, field size, SSD indicator check at the same time, and out put measurement was possible with the same set up, so daily Q.A time was reduced, and we were able to confirm an objective basis about each item measurement. As a result of having measured for four months, output measurement within ±2%, and measured laser alignment, field size, SSD indicator in range within ±1 mm. We can enforce output measurement and appliances check conveniently, and time was reduced and was able to raise efficiency of business. We were able to bring a cost reduction by substitution expensive commercialized equipment. Further It is necessary to makes a product as strong and slight materials, and improve convenience of use.

  3. Prevention of lingual calculus formation with daily use of 6% H2O2/2% pyrophosphate whitening strips.

    Science.gov (United States)

    Farrell, S; Barker, M L; Gerlach, R W; Putt, M S; Milleman, J L

    2009-01-01

    This randomized controlled clinical trial was conducted to evaluate whether daily use of a hydrogen peroxide/ pyrophosphate-containing antitartar whitening strip might safely yield clinical reductions in post-prophylaxis calculus accumulation. A three-month, randomized controlled trial was conducted to compare calculus accumulation with a daily 6% hydrogen peroxide/pyrophosphate strip versus regular brushing. After an eight-week run-in phase to identify calculus formers, a prophylaxis was administered, and 77 subjects were randomly assigned to daily strip or brushing only groups. All subjects received an anticavity dentifrice (Crest Cavity Protection) and manual brush for use throughout the three-month study; for subjects assigned to the experimental group, strip application was once daily for five minutes on the facial and lingual surfaces of the mandibular teeth. Efficacy was measured as mm calculus (VMI) before prophylaxis and after six and 12 weeks of treatment, while safety was assessed from examination and interview. Subjects ranged in age from 21-87 years, with groups balanced (p > 0.26) on pertinent demographic and behavioral parameters, and pre-prophylaxis calculus baseline mean scores (16.0 mm). At Week 6, calculus accumulation was lower in the strip group, with adjusted mean (SE) lingual VMI of 12.0 (0.87) for the strip group and 17.0 (0.88) for the brushing control. At Week 12, calculus accumulation was lower in the strip group, with adjusted mean (SE) lingual VMI of 14.3 (0.85) for the strip group and 17.2 (0.86) for the brushing control. Treatments differed significantly (p calculus accumulation at both time points. A total of three subjects (8%) in the strip group and two subjects (5%) in the brushing control had mild oral irritation or tooth sensitivity during treatment; no one discontinued early due to an adverse event. Daily use of hydrogen peroxide whitening strips with pyrophosphate reduced calculus formation by up to 29% versus regular brushing

  4. ONC201 Demonstrates Antitumor Effects in Both Triple-Negative and Non-Triple-Negative Breast Cancers through TRAIL-Dependent and TRAIL-Independent Mechanisms.

    Science.gov (United States)

    Ralff, Marie D; Kline, Christina L B; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T; Prabhu, Varun V; Oster, Wolfgang; El-Deiry, Wafik S

    2017-07-01

    Breast cancer is a major cause of cancer-related death. TNF-related apoptosis-inducing ligand (TRAIL) has been of interest as a cancer therapeutic, but only a subset of triple-negative breast cancers (TNBC) is sensitive to TRAIL. The small-molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here, we show that ONC201 is efficacious against both TNBC and non-TNBC cells ( n = 13). A subset of TNBC and non-TNBC cells succumbs to ONC201-induced cell death. In 2 of 8 TNBC cell lines, ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by TRAIL-neutralizing antibody RIK2. The proapoptotic effect of ONC201 translates to in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested (6/8), ONC201 has an antiproliferative effect but does not induce apoptosis. ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the G 1 phase of the cell cycle. pRb expression is associated with sensitivity to the antiproliferative effects of ONC201, and the compound synergizes with taxanes in less sensitive cells. All non-TNBC cells ( n = 5) are growth inhibited following ONC201 treatment, and unlike what has been observed with TRAIL, a subset ( n = 2) shows PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL independent. Our data demonstrate that ONC201 has potent antiproliferative and proapoptotic effects in a broad range of breast cancer subtypes, through TRAIL-dependent and TRAIL-independent mechanisms. These findings develop a preclinical rationale for developing ONC201 as a single agent and/or in combination with approved therapies in breast cancer. Mol Cancer Ther; 16(7); 1290-8. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yong-sheng Tu

    2017-10-01

    Full Text Available In multiple myeloma, despite recent improvements offered by new therapies, disease relapse and drug resistance still occur in the majority of patients. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. The imipridone ONC201 causes downstream inactivation of ERK1/2 signaling and has tumoricidal activity against a variety of tumor types, while its efficacy in preclinical models of myeloma remains unclear. In this study, we treated human myeloma cell lines and patient-derived tumor cells with ONC201. Treatment decreased cellular viability and induced apoptosis in myeloma cell lines, with IC50 values of 1 to 1.5 μM, even in those with high risk features or TP53 loss. ONC201 increased levels of the pro-apoptotic protein Bim in myeloma cells, resulting from decreased phosphorylation of degradation-promoting Bim Ser69 by ERK1/2. In addition, myeloma cell lines made resistant to several standard-of-care agents (by chronic exposure were equally sensitive to ONC201 as their drug-naïve counterparts, and combinations of ONC201 with proteasome inhibitors had synergistic anti-myeloma activity. Overall, these findings demonstrate that ONC201 kills myeloma cells regardless of resistance to standard-of-care therapies, making it promising for clinical testing in relapsed/refractory myeloma.

  6. Chemical and hydrothermal studies on once through boilers using a full scale replica

    International Nuclear Information System (INIS)

    Penfold, D.; Gill, G.M.; Greene, J.C.; Harrison, G.S.; Walker, M.A.

    1987-01-01

    The paper describes the scope of research work carried out on once through boilers on the test rig at Wythenshawe, United Kingdom. The latter rig was designed and built to replicate the chemical, metallurgical and hydrothermal conditions on single tube test sections of Heysham 1 (AGR) and Wylfa (Magnox) boilers. A description is given of the rig, along with the facilities for obtaining the research data. Research studies on the once through boilers include: Heysham 1 boiler inlet, oxygen stress corrosion risk in post trip operation, Wylfa two phase erosion-corrosion risk in post trip operation, Wylfa two phase erosion-corrosion, dryout phenomena in a helical coil, and heat transfer co-efficients. (UK)

  7. U.S. Daily Surface Data (COOP Daily/Summary of Day)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — U.S. Daily Surface Data consists of several closely related data sets: DSI-3200, DSI-3202, DSI-3206, and DSI-3210. These are archived at the National Climatic Data...

  8. Once-weekly albiglutide in the management of type 2 diabetes: patient considerations.

    Science.gov (United States)

    Woodward, Heather N; Anderson, Sarah L

    2014-01-01

    This review describes the pharmacologic, pharmacokinetic, and pharmacodynamic properties of albiglutide, as well as its clinical efficacy and safety. Albiglutide is a novel, once-weekly, injectable glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes. The European Commission recently granted marketing authorization for the drug in the European Union and on April 15, 2014, the US Food and Drug Administration approved albiglutide (Tanzeum™ [GlaxoSmithKline LLC, Wilmington, DE, USA]) to improve glycemic control in adults with type 2 diabetes. Albiglutide has been studied in Phase I, II, and III clinical trials. In the Phase III clinical trials, known as the Harmony series, weekly dosing of albiglutide demonstrated reductions in fasting plasma glucose, postprandial plasma glucose, and glycated hemoglobin, and was associated with weight loss. In all phases of the clinical trials, albiglutide administered once weekly showed a safety and tolerability profile similar to that of placebo, with mild gastrointestinal-related complaints and injection site erythema being the most commonly encountered adverse effects. Compared with pioglitazone and liraglutide, albiglutide has been shown to be clinically less effective. However, it offers the benefit of weight loss that pioglitazone does not, with fewer gastrointestinal side effects than liraglutide. As guidelines continue to advocate for patient-centered treatment strategies, once-weekly albiglutide will be an important addition to the growing armamentarium of treatment options for adults with type 2 diabetes needing target glycemic control.

  9. SU-F-T-470: Implementation of a Daily Quality Assurance Phantom for Six Degrees-Of-Freedom Couch Testing

    Energy Technology Data Exchange (ETDEWEB)

    Gaballa, H; O’Brien, M; Riegel, A; Jamshidi, A; Klein, E [Northwell Health, Lake Success, NY (United States)

    2016-06-15

    Purpose: To develop a daily quality assurance (QA) device that can test the 6DoF (degrees of freedom) couch repositioning accuracy, prior to SBRT treatment deliveries, with an accuracy of ±0.3 degrees and ±0.3 mm. Methods: A daily QA phantom is designed with a focus on the derived center of projections of its markers, rather than tracking its individual markers one at a time. This approach can be the most favorable to address the intended machining accuracy of the QA phantom and the CBCT spatial resolution limitations, primarily 1 mm min slice thickness, simultaneously. With the current design, ±0.1 mm congruence of the resultant center of gravity of the markers with reference CT (0.6 mm minimum slice thickness) vs CBCT (1.0 mm minimum slice thickness) can be achieved. If successful, the QA device should be qualified to test 6DoF couch performance with a gauged accuracy of ±0.3 degrees/±0.3 mm. Testing is performed for the Varian True Beam 2.0 6DoF system. Results: Once the QA phantom is constructed and tested, agreement of the center of gravity of the reference CT scan and the CBCT scan of ±0.1 mm is achieved. This has translated into a consistent 3D-3D match on the treatment machine, CT vs CBCT, with a repetitive ±0.1 mm variation, thus exceeding our expectations. We have deployed the phantom for daily QA on one of our accelerators, and found that the QA time has increased by only 10 minutes. Conclusion: A 6DoF phantom has been designed (patent pending) and built with a realistic work flow in mind where the daily couch accuracy QA checks taking less than 10 minutes. Current developments include integration with the Varian’s Machine Performance Check consistency module.

  10. "Self-critical perfectionism, daily stress, and disclosure of daily emotional events": Correction to Richardson and Rice (2015).

    Science.gov (United States)

    2016-01-01

    Reports an error in "Self-critical perfectionism, daily stress, and disclosure of daily emotional events" by Clarissa M. E. Richardson and Kenneth G. Rice (Journal of Counseling Psychology, 2015[Oct], Vol 62[4], 694-702). In the article, the labels of the two lines in Figure 1 were inadvertently transposed. The dotted line should be labeled High SCP and the solid line should be labeled Low SCP. The correct version is present in the erratum. (The following abstract of the original article appeared in record 2015-30890-001.) Although disclosure of stressful events can alleviate distress, self-critical perfectionism may pose an especially strong impediment to disclosure during stress, likely contributing to poorer psychological well-being. In the current study, after completing a measure of self-critical perfectionism (the Discrepancy subscale of the Almost Perfect Scale-Revised; Slaney, Rice, Mobley, Trippi, & Ashby, 2001), 396 undergraduates completed measures of stress and disclosure at the end of each day for 1 week. Consistent with hypotheses and previous research, multilevel modeling results indicated significant intraindividual coupling of daily stress and daily disclosure where disclosure was more likely when experiencing high stress than low stress. As hypothesized, Discrepancy moderated the relationship between daily stress and daily disclosure. Individuals higher in self-critical perfectionism (Discrepancy) were less likely to engage in disclosure under high stress, when disclosure is often most beneficial, than those with lower Discrepancy scores. These results have implications for understanding the role of stress and coping in the daily lives of self-critical perfectionists. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  11. Pegylated Long-Acting Human Growth Hormone Possesses a Promising Once-Weekly Treatment Profile, and Multiple Dosing Is Well Tolerated in Adult Patients with Growth Hormone Deficiency

    DEFF Research Database (Denmark)

    Søndergaard, Esben; Klose, Marianne Christina; Hansen, Mette

    2011-01-01

    Background: Recombinant human GH (rhGH) replacement therapy in children and adults currently requires daily sc injections for several years or lifelong, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed for once-weekly administration. Objectives......: Our objective was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of NNC126-0083 in adult patients with GH deficiency (GHD). Subjects and Methods: Thirty-three adult patients with GHD, age 20-65 yr, body mass index 18.5-35.0 kg/m(2), and glycated...... to 240 h after the third dosing. Physical examination, antibodies, and local tolerability were assessed. Results: NNC126-0083 was well tolerated with no difference in local tolerability compared with placebo and with no signs of lipoatrophy. A more than dose-proportional exposure was observed...

  12. CDC WONDER: Daily Fine Particulate Matter

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Daily Fine Particulate Matter data available on CDC WONDER are geographically aggregated daily measures of fine particulate matter in the outdoor air, spanning...

  13. Global Daily Climatology Network: Kazakhstan subset

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset is a compilation of in situ daily meteorological observations for Kazakhstan within the framework of joint efforts to create Global Daily Climatology...

  14. Estimation of daily albedo on Tottori sand surface

    International Nuclear Information System (INIS)

    Gu, S.; Otsuki, K.; Kamichika, M.

    2001-01-01

    Daily albedos of a bare sand surface were measured with a solarimeter (Eko MS-62) between 23 August and 30 November in 1997 at Tottori sand dune, Japan. These quickly decreased on rainy days, and recovered during dry spells (days between rainfalls). A strong exponential relationship was found between daily albedos and the number of dry days. The daily albedos on dry days also showed a direct relationship with daily transmissivities in the range less than 0.55. Two simple models were developed to estimate daily albedos for dry spell days on bare Tottori sand surface using routine meteorological data. Daily albedos were calculated using these two models, and compared with the measured daily albedos. For Model #1, the daily albedos were successfully predicted only using the number of dry spell days; the correlation coefficient between the estimated and measured albedo was 0.73, and the standard error was 1.2%. For Model #2, the number of dry spell days and transmissivity were considered in order to calculate the daily albedo on dry spell days; the correlation coefficient was 0.85, and the standard error was 0.9%. Estimated albedos were in good agreement with measured albedos. (author)

  15. Treatment of scalp psoriasis with clobetasol-17 propionate 0.05% shampoo: a study on daily clinical practice.

    Science.gov (United States)

    Bovenschen, H J; Van de Kerkhof, P C M

    2010-04-01

    Safety and clinical effectiveness of clobetasol-17 propionate 0.05% shampoo have been shown in patients with scalp psoriasis. First, to evaluate treatment satisfaction, user convenience safety and effectiveness of clobetasol-17 propionate 0.05% shampoo treatment in daily clinical practice. Second, to identify subgroup variables that may predict treatment success or failure. A total of 56 patients with scalp psoriasis were treated with short-contact clobetasol-17 propionate 0.05% shampoo once daily for 4 weeks. Data on treatment satisfaction, user convenience, safety and effectiveness were assessed on a 7-point Likert scale using postal questionnaires. Subgroup analyses were performed to identify variables that may predict treatment outcome. A total of 41 patients returned both questionnaires (73%). Positive treatment satisfaction and user convenience were reported by 66% and 79% of patients respectively. Patient-rated indicators for disease severity improved by 39-46% (P 0.05). Short-contact treatment with clobetasol-17 propionate 0.05% shampoo has high user convenience and patient satisfaction rates. Moreover, the treatment is well-tolerated and efficacious from patients' perspective. Subgroup analyses did not reveal factors predicting treatment outcome, although treatment success tended to be more evident in patients who had received fewer treatments previously.

  16. Reduction of salivary mutans streptococci in orthodontic patients during daily consumption of yoghurt containing probiotic bacteria

    DEFF Research Database (Denmark)

    Cildir, Sule Kavaloglu; Germec, Derya; Sandalli, Nuket

    2009-01-01

    Previous studies have suggested that probiotic supplements in dairy products may affect the oral microbial ecology, but the effect in orthodontic patients has not previously been reported. The aim of the present study was to examine whether short-term consumption of fruit yogurt containing....... During periods 2 and 4 (2 weeks each), the subjects ingested 200 g fruit yogurt containing Bifidobacterium animalis subsp. lactis DN-173010 (2 x 10(8) colony forming units/g) once daily or a control yogurt without viable bacteria. Periods 1 and 3 were run-in and wash-out periods of 1 and 6 weeks......, respectively. Salivary mutans streptococci and lactobacilli were enumerated with chair-side kits before and after the yogurt consumption periods. Pre- and post-treatment values within each regimen were compared with a two-tailed marginal homogeneity test for categorical data. A statistically significant...

  17. Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients: a randomized double-blind study.

    Science.gov (United States)

    Lundholm, Kent; Gunnebo, Lena; Körner, Ulla; Iresjö, Britt-Marie; Engström, Cecilia; Hyltander, Anders; Smedh, Ulrika; Bosaeus, Ingvar

    2010-04-15

    The short-term provision of ghrelin to patients with cancer indicates that there may be benefits from long-term provision of ghrelin for the palliative treatment of weight-losing cancer patients. This hypothesis was evaluated in a randomized, double-blind, phase 2 study. Weight-losing cancer patients with solid gastrointestinal tumors were randomized to receive either high-dose ghrelin treatment (13 microg/kg daily; n = 17 patients) or low-dose ghrelin treatment (0.7 microg/kg daily; n = 14 patients) for 8 weeks as a once-daily, subcutaneous injections. Appetite was scored on a visual analog scale; and food intake, resting energy expenditure, and body composition (dual x-ray absorpitometry) were measured before the start of treatment and during follow-up. Serum levels of ghrelin, insulin, insulin-like growth factor 1, growth hormone (GH), triglycerides, free fatty acids, and glucose were measured. Health-related quality of life, anxiety, and depression were assessed by using standardized methods (the 36-item Short Form Health Survey and the Hospital Anxiety and Depression Scale). Physical activity, rest, and sleep were measured by using a multisensor body monitor. Treatment groups were comparable at inclusion. Appetite scores were increased significantly by high-dose ghrelin analyzed both on an intent-to-treat basis and according to the protocol. High-dose ghrelin reduced the loss of whole body fat (P losing cancer patients with solid tumors supports host metabolism, improves appetite, and attenuates catabolism. (c) 2010 American Cancer Society.

  18. Model‐Informed Development and Registration of a Once‐Daily Regimen of Extended‐Release Tofacitinib

    Science.gov (United States)

    Lamba, M; Hutmacher, MM; Furst, DE; Dikranian, A; Dowty, ME; Conrado, D; Stock, T; Nduaka, C; Cook, J

    2017-01-01

    Extended‐release (XR) formulations enable less frequent dosing vs. conventional (e.g., immediate release (IR)) formulations. Regulatory registration of such formulations typically requires pharmacokinetic (PK) and clinical efficacy data. Here we illustrate a model‐informed, exposure–response (E‐R) approach to translate controlled trial data from one formulation to another without a phase III trial, using a tofacitinib case study. Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). E‐R analyses were conducted using validated clinical endpoints from phase II dose–response and nonclinical dose fractionation studies of the IR formulation. Consistent with the delay in clinical response dynamics relative to PK, average concentration was established as the relevant PK parameter for tofacitinib efficacy and supported pharmacodynamic similarity. These evaluations, alongside demonstrated equivalence in total systemic exposure between IR and XR formulations, provided the basis for the regulatory approval of tofacitinib XR once daily by the US Food and Drug Administration. PMID:27859030

  19. Lightship Daily Observations

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Observations taken on board lightships along the United States coasts from 1936 - 1983. Generally 4-6 observations daily. Also includes deck logs, which give...

  20. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.

    Directory of Open Access Journals (Sweden)

    J Gerardo García-Lerma

    2008-02-01

    Full Text Available In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission.We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC, group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF, and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4 received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively. All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected.This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities.

  1. Supercritical-pressure, once-through cycle light water cooled reactor concept

    International Nuclear Information System (INIS)

    Oka, Yoshiaki; Koshizuka, Seiichi

    2001-01-01

    The purpose of the study is to develop new reactor concepts for the innovation of light water reactors (LWR) and fast reactors. Concept of the once-through coolant cycle, supercritical-pressure light water cooled reactor was developed. Major aspects of reactor design and safety were analysed by the computer codes which were developed by ourselves. It includes core design of thermal and fast reactors, plant system, safety criteria, accident and transient analysis, LOCA, PSA, plant control, start up and stability. High enthalpy rise as supercritical boiler was achieved by evaluating the cladding temperature directly during transients. Fundamental safety principle of the reactor is monitoring coolant flow rate instead of water level of LWR. The reactor system is compact and simple because of high specific enthalpy of supercritical water and the once-through cycle. The major components are similar to those of LWR and supercritical thermal plant. Their temperature are within the experiences in spite of the high outlet coolant temperature. The reactor is compatible with tight fuel lattice fast reactor because of the high head pumps and low coolant flow rate. The power rating of the fast reactor is higher than the that of thermal reactor because of the high power density. (author)

  2. ONC201 Targets AR and AR-V7 Signaling, Reduces PSA, and Synergizes with Everolimus in Prostate Cancer.

    Science.gov (United States)

    Lev, Avital; Lulla, Amriti R; Ross, Brian C; Ralff, Marie D; Makhov, Petr B; Dicker, David T; El-Deiry, Wafik S

    2018-05-01

    Androgen receptor (AR) signaling plays a key role in prostate cancer progression, and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen for patients with advanced disease. Unfortunately, most prostate cancers eventually become androgen-independent and resistant to ADT with patients progressing to metastatic castration-resistant prostate cancer (mCRPC). Constitutively activated AR variants (AR-V) have emerged as mediators of resistance to AR-targeted therapy and the progression of mCRPC, and they represent an important therapeutic target. Out of at least 15 AR-Vs described thus far, AR-V7 is the most abundant, and its expression correlates with ADT resistance. ONC201/TIC10 is the founding member of the imipridone class of small molecules and has shown anticancer activity in a broad range of tumor types. ONC201 is currently being tested in phase I/II clinical trials for advanced solid tumors, including mCRPC, and hematologic malignancies. There has been promising activity observed in patients in early clinical testing. This study demonstrates preclinical single-agent efficacy of ONC201 using in vitro and in vivo models of prostate cancer. ONC201 has potent antiproliferative and proapoptotic effects in both castration-resistant and -sensitive prostate cancer cells. Furthermore, the data demonstrate that ONC201 downregulates the expression of key drivers of prostate cancer such as AR-V7 and downstream target genes including the clinically used biomarker PSA (KLK3). Finally, the data also provide a preclinical rationale for combination of ONC201 with approved therapeutics for prostate cancer such as enzalutamide, everolimus (mTOR inhibitor), or docetaxel. Implications: The preclinical efficacy of ONC201 as a single agent or in combination, in hormone-sensitive or castration-resistant prostate cancer, suggests the potential for immediate clinical translation. Mol Cancer Res; 16(5); 754-66. ©2018 AACR . ©2018 American Association for Cancer

  3. The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma.

    Science.gov (United States)

    Tu, Yong-Sheng; He, Jin; Liu, Huan; Lee, Hans C; Wang, Hua; Ishizawa, Jo; Allen, Joshua E; Andreeff, Michael; Orlowski, Robert Z; Davis, Richard E; Yang, Jing

    2017-10-01

    In multiple myeloma, despite recent improvements offered by new therapies, disease relapse and drug resistance still occur in the majority of patients. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. The imipridone ONC201 causes downstream inactivation of ERK1/2 signaling and has tumoricidal activity against a variety of tumor types, while its efficacy in preclinical models of myeloma remains unclear. In this study, we treated human myeloma cell lines and patient-derived tumor cells with ONC201. Treatment decreased cellular viability and induced apoptosis in myeloma cell lines, with IC50 values of 1 to 1.5 μM, even in those with high risk features or TP53 loss. ONC201 increased levels of the pro-apoptotic protein Bim in myeloma cells, resulting from decreased phosphorylation of degradation-promoting Bim Ser69 by ERK1/2. In addition, myeloma cell lines made resistant to several standard-of-care agents (by chronic exposure) were equally sensitive to ONC201 as their drug-naïve counterparts, and combinations of ONC201 with proteasome inhibitors had synergistic anti-myeloma activity. Overall, these findings demonstrate that ONC201 kills myeloma cells regardless of resistance to standard-of-care therapies, making it promising for clinical testing in relapsed/refractory myeloma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Comparison of three methods to reduce energy density. Effects on daily energy intake.

    Science.gov (United States)

    Williams, Rachel A; Roe, Liane S; Rolls, Barbara J

    2013-07-01

    Reductions in food energy density can decrease energy intake, but it is not known if the effects depend on the way that energy density is reduced. We investigated whether three methods of reducing energy density (decreasing fat, increasing fruit and vegetables, and adding water) differed in their effects on energy intake across the day. In a crossover design, 59 adults ate breakfast, lunch, and dinner in the laboratory once a week for 4 weeks. Across conditions, the entrées were either standard in energy density or were reduced in energy density by 20% using one of the three methods. Each meal included a manipulated entrée along with unmanipulated side dishes, and all foods were consumed ad libitum. Reducing the energy density of entrées significantly decreased daily energy intake compared to standard entrées (mean intake 2667 ± 77 kcal/day; 11,166 ± 322 kJ/day). The mean decrease was 396 ± 44 kcal/day (1658 ± 184 kJ/day) when fat was reduced, 308 ± 41 kcal/day (1290 ± 172 kJ/day) when fruit and vegetables were increased, and 230 ± 35 kcal/day (963 ± 147 kJ/day) when water was added. Daily energy intake was lower when fat was decreased compared to the other methods. These findings indicate that a variety of diet compositions can be recommended to reduce overall dietary energy density in order to moderate energy intake. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies.

    Science.gov (United States)

    Ishizawa, Jo; Kojima, Kensuke; Chachad, Dhruv; Ruvolo, Peter; Ruvolo, Vivian; Jacamo, Rodrigo O; Borthakur, Gautam; Mu, Hong; Zeng, Zhihong; Tabe, Yoko; Allen, Joshua E; Wang, Zhiqiang; Ma, Wencai; Lee, Hans C; Orlowski, Robert; Sarbassov, Dos D; Lorenzi, Philip L; Huang, Xuelin; Neelapu, Sattva S; McDonnell, Timothy; Miranda, Roberto N; Wang, Michael; Kantarjian, Hagop; Konopleva, Marina; Davis, R Eric; Andreeff, Michael

    2016-02-16

    The clinical challenge posed by p53 abnormalities in hematological malignancies requires therapeutic strategies other than standard genotoxic chemotherapies. ONC201 is a first-in-class small molecule that activates p53-independent apoptosis, has a benign safety profile, and is in early clinical trials. We found that ONC201 caused p53-independent apoptosis and cell cycle arrest in cell lines and in mantle cell lymphoma (MCL) and acute myeloid leukemia (AML) samples from patients; these included samples from patients with genetic abnormalities associated with poor prognosis or cells that had developed resistance to the nongenotoxic agents ibrutinib and bortezomib. Moreover, ONC201 caused apoptosis in stem and progenitor AML cells and abrogated the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. ONC201 caused changes in gene expression similar to those caused by the unfolded protein response (UPR) and integrated stress responses (ISRs), which increase the translation of the transcription factor ATF4 through an increase in the phosphorylation of the translation initiation factor eIF2α. However, unlike the UPR and ISR, the increase in ATF4 abundance in ONC201-treated hematopoietic cells promoted apoptosis and did not depend on increased phosphorylation of eIF2α. ONC201 also inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling, likely through ATF4-mediated induction of the mTORC1 inhibitor DDIT4. Overexpression of BCL-2 protected against ONC201-induced apoptosis, and the combination of ONC201 and the BCL-2 antagonist ABT-199 synergistically increased apoptosis. Thus, our results suggest that by inducing an atypical ISR and p53-independent apoptosis, ONC201 has clinical potential in hematological malignancies. Copyright © 2016, American Association for the Advancement of Science.

  6. Daily Weather Maps

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Several different government offices have published the Daily weather maps over its history. The publication has also gone by different names over time. The U.S....

  7. Role of once-daily glycopyrronium bromide (NVA237 in the management of COPD

    Directory of Open Access Journals (Sweden)

    D’Urzo A

    2013-08-01

    Full Text Available Anthony D'UrzoDepartment of Family and Community Medicine, University of Toronto, Toronto, ON, CanadaAbstract: Progressive airflow limitation is a hallmark feature of chronic obstructive pulmonary disease (COPD that ultimately leads to breathlessness, impaired quality of life, and reduced exercise capacity. Pharmacotherapy is used in patients with COPD to prevent and control symptoms, reduce both the frequency and severity of exacerbations, improve health status, and increase exercise tolerance. These strategies are intended to address management issues which promote both current disease control and a reduction in the risk of disease deterioration in the future. At the present time, long-acting β2-agonists (LABAs and long-acting muscarinic antagonists (LAMAs are available for maintenance therapy in patients with persistent symptoms. Tiotropium was the first LAMA to be approved for management of COPD, and many studies have described its beneficial effects on multiple clinically relevant outcomes. Glycopyrronium bromide (NVA237, a new LAMA, has been developed and received regulatory approval for management of COPD in a number of countries around the world. Results from pivotal Phase III trials suggest that NVA237 is safe and well tolerated in patients with moderate to severe COPD, and provides rapid and sustained improvements in lung function. Further, these changes are associated with statistically and clinically meaningful improvements in dyspnea, health-related quality of life, and exercise tolerance. Treatment with NVA237 also results in a significant reduction in risk of exacerbations and the need for rescue medication, and has been comparable with tiotropium with respect to safety and efficacy outcomes. Finally, emerging data indicate that NVA237 is efficacious both as monotherapy and in combination with indacaterol.Keywords: glycopyrronium bromide, NVA237, chronic obstructive pulmonary disease, inhaled long-acting bronchodilators

  8. ONC201 demonstrates anti-tumor effects in both triple negative and non-triple negative breast cancers through TRAIL-dependent and TRAIL-independent mechanisms

    Science.gov (United States)

    Ralff, Marie D.; Kline, Christina L.B.; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T.; Prabhu, Varun V.; Oster, Wolfgang; El-Deiry, Wafik S.

    2017-01-01

    Breast cancer is a major cause of cancer-related death. TRAIL has been of interest as a cancer therapeutic, but only a subset of triple negative breast cancers (TNBC) is sensitive to TRAIL. The small molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here we show that ONC201 is efficacious against both TNBC and non-TNBC cells (n=13). A subset of TNBC and non-TNBC cells succumb to ONC201-induced cell death. In 2/8 TNBC cell lines, ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by TRAIL-neutralizing antibody RIK2. The pro-apoptotic effect of ONC201 translates to in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested (6/8) ONC201 has an anti-proliferative effect but does not induce apoptosis. ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the G1 phase of the cell cycle. pRb expression is associated with sensitivity to the anti-proliferative effects of ONC201, and the compound synergizes with taxanes in less sensitive cells. All non-TNBC cells (n=5) are growth inhibited following ONC201 treatment, and unlike what has been observed with TRAIL, a subset (n=2) show PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL-independent. Our data demonstrate that ONC201 has potent anti-proliferative and pro-apoptotic effects in a broad range of breast cancer subtypes, through TRAIL-dependent and TRAIL-independent mechanisms. These findings develop a pre-clinical rationale for developing ONC201 as a single agent and/or in combination with approved therapies in breast cancer. PMID:28424227

  9. Primary headache diagnosis among chronic daily headache patients

    Directory of Open Access Journals (Sweden)

    Krymchantowski Abouch Valenty

    2003-01-01

    Full Text Available Chronic daily headache (CDH refers to a group of non-paroxysmal daily or near-daily headaches with peculiar characteristics that are highly prevalent in populations of neurological clinics and not uncommon among non-patient populations. Most of the patients with CDH had, as primary diagnosis, episodic migraine, which, with the time, presented a progressive frequency, pattern modification and loss of specific migraine characteristics. Other CDH patients had chronic tension-type headache, new daily persistent headache and hemicrania continua, which evolved thru the time to the daily or near-daily presentation. The objective of this study was to determine the primary headache diagnosis among a population of chronic daily headache patients attending a tertiary center for headache treatment. During a 5-year period 651 consecutive chronic daily headache patients attending a private subspecialty center were studied prospectively. The criteria adopted were those proposed by Silberstein et al (1994, revised 1996. Five hundred seventy four patients (88.1% had episodic migraine as primary headache before turning into daily presentation, 52 (8% had chronic tension-type headache, 14 (2.2% had hemicrania continua and 11 patients (1.7% had new daily persistent headache. CDH is quite frequent in patients from clinic-based studies suggesting a high degree of disability. Emphasis on education of patients suffering from frequent primary headaches with regard to measures that are able to decrease suffering and disability as well as better medical education directed to more efficient ways to handle these patients are necessary to improve outcome of such a prevalent condition.

  10. Comparison of the evolution of tumor cells after unique and multiple (accelerated) daily irradiation in mammary carcinoma of C3H mice

    International Nuclear Information System (INIS)

    Pfersdorff, J.; Sack, H.

    1986-01-01

    The comparison of two fractionation schemes, i.e. the usual irradiation once a day with 2 Gy (SDF) and the fractionation with 3 times 1.6 Gy per day (MDF) at intervals of at least four hours shows the stronger action of higher fractionation on the destruction of tumor cells and the inhibition of their proliferation kinetics. So the number of pycnotic cells is considerably increased in case of multiple daily irradiation, and the mitosis rate as well as the labelling index show a more significant decrease. In case of one irradiation per day, the number of pycnotic cells increases during radiotherapy, too, but the mitosis rate and the labelling index only decrease until the fifth or sixth treatment day, remaining then unchanged or increasing slightly. This suggests a recurring multiplication of tumor cells already during radiotherapy. The higher efficacy of multiple daily fractionation in rapidly proliferating tumors is proved by the measurements of changing tumor volumes in the living animal during irradiation as well as by the observation of the survival time after irradiation. (orig.) [de

  11. Anti-pancreatic cancer activity of ONC212 involves the unfolded protein response (UPR) and is reduced by IGF1-R and GRP78/BIP.

    Science.gov (United States)

    Lev, Avital; Lulla, Amriti R; Wagner, Jessica; Ralff, Marie D; Kiehl, Joshua B; Zhou, Yan; Benes, Cyril H; Prabhu, Varun V; Oster, Wolfgang; Astsaturov, Igor; Dicker, David T; El-Deiry, Wafik S

    2017-10-10

    Pancreatic cancer is chemo-resistant and metastasizes early with an overall five-year survival of ∼8.2%. First-in-class imipridone ONC201 is a small molecule in clinical trials with anti-cancer activity. ONC212, a fluorinated-ONC201 analogue, shows preclinical efficacy in melanoma and hepatocellular-cancer models. We investigated efficacy of ONC201 and ONC212 against pancreatic cancer cell lines ( N =16 including 9 PDX-cell lines). We demonstrate ONC212 efficacy in 4 in-vivo models including ONC201-resistant tumors. ONC212 is active in pancreatic cancer as single agent or in combination with 5-fluorouracil, irinotecan, oxaliplatin or RTK inhibitor crizotinib. Based on upregulation of pro-survival IGF1-R in some tumors, we found an active combination of ONC212 with inhibitor AG1024, including in vivo . We show a rationale for targeting pancreatic cancer using ONC212 combined with targeting the unfolded-protein response and ER chaperones such as GRP78/BIP. Our results lay the foundation to test imipridones, anti-cancer agents, in pancreatic cancer, that is refractory to most drugs.

  12. Never, non-daily, and daily smoking status and progression to daily cigarette smoking as correlates of major depressive episode in a national sample of youth: Results from the National Survey of Drug Use and Health 2013 to 2015.

    Science.gov (United States)

    Cohn, Amy M

    2018-09-01

    Cigarette smoking is associated with depression, and new initiates who progress more quickly to daily smoking may be at enhanced risk. In a nationally representative sample of youth, this study examined the association between daily, non-daily, and never smoking with past-year and lifetime major depressive episode (MDE) and, among daily smokers, whether faster progression to daily smoking was associated with increased MDE risk. Data were from n = 44,921 youth aged 12-17 in the 2013-2015 National Survey on Drug Use and Health. Weighted adjusted multivariable logistic regression models were used to examine the association of smoking status (daily, non-daily, never) with lifetime and past-year MDE, and the association between progression from cigarette trial to daily smoking with MDE outcomes among daily smokers. Daily and non-daily smokers had similar rates of lifetime and past-year MDE; rates of MDE were approximately 50% lower among never smokers. Compared to never smokers, adjusted models showed that non-daily smokers had a higher risk of past-year and lifetime MDE, while daily smokers had a higher risk of past-year but not lifetime MDE. Daily smoking youth who progressed more quickly from cigarette trial to daily use had an increased risk of both lifetime and past-year MDE. Prevention programs should target factors associated with the shift from cigarette experimentation to regular use to curb deleterious consequences of use. Copyright © 2018. Published by Elsevier Ltd.

  13. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

    Directory of Open Access Journals (Sweden)

    Kim JY

    2015-01-01

    Full Text Available Ju-Young Kim,1,* Sung-Hoon Lee,2,3,* Chun-Woong Park,4 Yun-Seok Rhee,5 Dong-Wook Kim,6 Junsang Park,3 Moonseok Lee,3 Jeong-Woong Seo,2 Eun-Seok Park2 1College of Pharmacy, Woosuk University, Wanju-gun, Republic of Korea; 2School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 3GL Pharmtech, Seongnam, Republic of Korea; 4College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea; 5College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Republic of Korea; 6Department of Pharmaceutical Engineering, Cheongju University, Cheongju, Republic of Korea *These authors contributed equally to this work Abstract: The aim of present study was to design oxycodone once-a-day controlled-release (CR tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day] or once-a-day CR tablets (20 mg were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. Keywords

  14. Chronic job burnout and daily functioning: A theoretical analysis

    Directory of Open Access Journals (Sweden)

    Arnold B. Bakker

    2014-12-01

    Full Text Available In this article, we discuss the individual employee's role in the development of his/her job burnout. We review the antecedents and consequences of burnout, and propose a model with chronic burnout as a moderator of daily functioning in the workplace. Specifically, we argue that chronic burnout strengthens the loss cycle of daily job demands, daily exhaustion, and daily self-undermining. Additionally, we argue that chronic burnout weakens the gain cycle of daily job resources, daily work engagement, and daily job crafting. We conclude that employees with high levels of burnout need help in structurally changing their working conditions and health status.

  15. On polar daily geomagnetic variation

    Directory of Open Access Journals (Sweden)

    Paola De Michelis

    2015-11-01

    Full Text Available The aim of this work is to investigate the nature of the daily magnetic field perturbations produced by ionospheric and magnetospheric currents at high latitudes. We analyse the hourly means of the X and Y geomagnetic field components recorded by a meridian chain of permanent geomagnetic observatories in the polar region of the Northern Hemisphere during a period of four years (1995-1998 around the solar minimum. We apply a mathematical method, known as natural orthogonal component (NOC, which is capable of characterizing the dominant modes of the geomagnetic field daily variability through a set of empirical orthogonal functions (EOFs. Using the first two modes we reconstruct a two-dimensional equivalent current representation of the ionospheric electric currents, which contribute substantially to the geomagnetic daily variations. The obtained current structures resemble the equivalent current patterns of DP2 and DP1. We characterize these currents by studying their evolution with the geomagnetic activity level and by analysing their dependence on the interplanetary magnetic field. The obtained results support the idea of a coexistence of two main processes during all analysed period although one of them, the directly driven process, represents the dominant component of the geomagnetic daily variation.

  16. The effect of a corticosteroid cream and a barrier-strengthening moisturizer in hand eczema. A double-blind, randomized, prospective, parallel group clinical trial.

    Science.gov (United States)

    Lodén, M; Wirén, K; Smerud, K T; Meland, N; Hønnås, H; Mørk, G; Lützow-Holm, C; Funk, J; Meding, B

    2012-05-01

    Hand eczema is a common and persistent disease with a relapsing course. Clinical data suggest that once daily treatment with corticosteroids is just as effective as twice daily treatment. The aim of this study was to compare once and twice daily applications of a strong corticosteroid cream in addition to maintenance therapy with a moisturizer in patients with a recent relapse of hand eczema. The study was a parallel, double-blind, randomized, clinical trial on 44 patients. Twice daily application of a strong corticosteroid cream (betamethasone valerate 0.1%) was compared with once daily application, where a urea-containing moisturizer was substituted for the corticosteroid cream in the morning. The investigator scored the presence of eczema and the patients judged the health-related quality of life (HRQoL) using the Dermatology Life Quality Index (DLQI), which measures how much the patient's skin problem has affected his/her life over the past week. The patients also judged the severity of their eczema daily on a visual analogue scale. Both groups improved in terms of eczema and DLQI. However, the clinical scoring demonstrated that once daily application of corticosteroid was superior to twice daily application in diminishing eczema, especially in the group of patients with lower eczema scores at inclusion. Twice daily use of corticosteroids was not superior to once daily use in treating eczema. On the contrary, the clinical assessment showed a larger benefit from once daily treatment compared with twice daily, especially in the group of patients with a moderate eczema at inclusion. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

  17. Imiquimod 3.75% Cream Applied Daily to Treat Anogenital Warts: Combined Results from Women in Two Randomized, Placebo-Controlled Studies

    Directory of Open Access Journals (Sweden)

    David A. Baker

    2011-01-01

    Full Text Available Objective. To evaluate if new imiquimod formulations using a shorter treatment duration are safe and efficacious to treat anogenital warts. Methods. In two studies 534 women ≥12 years of age (mean 33.4 with 2–30 warts (mean 7.9 and total wart area ≥10 mm2 (mean 166.3 were randomized (1 : 2 : 2 to placebo (106, imiquimod 2.5% (212 or 3.75% (216 creams applied once daily until complete clearance or a maximum of 8 weeks. Results. For placebo, imiquimod 2.5% and 3.75%, respectively, complete clearance of all warts was achieved in 14.2%, 28.3%, and 36.6% of women (intent-to-treat, P=0.008 imiquimod 2.5%, and P<0.001 3.75% versus placebo. Mean changes in wart counts were −10.7%, −50.9%, and −63.5% (per-protocol, P<0.001 each active versus placebo and safety-related discontinuation rates 0.9%, 1.4%, and 2.3%. Conclusions. Imiquimod 3.75% applied daily for up to 8 weeks was well tolerated and superior to placebo in treating women with external anogenital warts.

  18. RESEARCH ON WEIGHT EVOLUTION AND DAILY AVERAGE INCREASE TO FOUR DIFFERENT GROUPS OF LITTLE CROSSBREED BULLS EXPOSED TO INTENSIVE FATTENING

    Directory of Open Access Journals (Sweden)

    I.R. MOLDOVAN

    2009-10-01

    Full Text Available Research aimed to highlight the weight differences and daily growth average of four groups of little crossbreed bulls raised in the same environmental conditions and having the same feeding diet. Farm in which they do research is TCE 3 abis SRL Piatra Neamt, located in Zanesti village at 14 km from the city of Piatra Neamt. Location of the farm is on the old IAS Zanesti and is endowed eight shelters from which two are still functional. Shelters are divided into collective lumber rooms, on which are housed an optimal number of calves depending on their age, number varied from 25 calves at 0 - 3 months up to 6 heads during growing and finishing period when they reach weights of 600-700 kg. Farm population is obtained with calves from reformed cows from milk farm belonging to the same company. Forage base is provided from the company's vegetable farm, farm exploits about 14,000 ha of arable land in Neamt County. Feeding (in three phases is made with the technological trailer once-daily in morning and drinking is made at discretion at constant.

  19. Anti-pancreatic cancer activity of ONC212 involves the unfolded protein response (UPR) and is reduced by IGF1-R and GRP78/BIP

    OpenAIRE

    Lev, Avital; Lulla, Amriti R.; Wagner, Jessica; Ralff, Marie D.; Kiehl, Joshua B.; Zhou, Yan; Benes, Cyril H.; Prabhu, Varun V.; Oster, Wolfgang; Astsaturov, Igor; Dicker, David T.; El-Deiry, Wafik S.

    2017-01-01

    Pancreatic cancer is chemo-resistant and metastasizes early with an overall five-year survival of ∼8.2%. First-in-class imipridone ONC201 is a small molecule in clinical trials with anti-cancer activity. ONC212, a fluorinated-ONC201 analogue, shows preclinical efficacy in melanoma and hepatocellular-cancer models. We investigated efficacy of ONC201 and ONC212 against pancreatic cancer cell lines (N=16 including 9 PDX-cell lines). We demonstrate ONC212 efficacy in 4 in-vivo models including ON...

  20. Stochastic modelling of daily rainfall sequences

    NARCIS (Netherlands)

    Buishand, T.A.

    1977-01-01

    Rainfall series of different climatic regions were analysed with the aim of generating daily rainfall sequences. A survey of the data is given in I, 1. When analysing daily rainfall sequences one must be aware of the following points:
    a. Seasonality. Because of seasonal variation

  1. Daily Interpersonal and Affective Dynamics in Personality Disorder

    Science.gov (United States)

    Wright, Aidan G.C.; Hopwood, Christopher J.; Simms, Leonard J.

    2015-01-01

    In this naturalistic study we adopt the lens of interpersonal theory to examine between-and within-person differences in dynamic processes of daily affect and interpersonal behaviors among individuals (N = 101) previously diagnosed with personality disorders who completed daily diaries over the course of 100 days. Dispositional ratings of interpersonal problems and measures of daily stress were used as predictors of daily shifts in interpersonal behavior and affect in multilevel models. Results indicate that ~40%–50% of the variance in interpersonal behavior and affect is due to daily fluctuations, which are modestly related to dispositional measures of interpersonal problems but strongly related to daily stress. The findings support conceptions of personality disorders as a dynamic form of psychopathology involving the individuals interacting with and regulating in response to the contextual features of their environment. PMID:26200849

  2. Spectral shift controlled reactor, UO2 once-through cycle optimized

    International Nuclear Information System (INIS)

    1978-05-01

    This paper presents technical and economic data on the SSCR which may be of use in the International Fuel Cycle Evaluation Program to intercompare alternative nuclear systems. Included in this data is information on the optimized UO 2 once-through fuel cycle. The ''optimized'' cycle refers to a UO 2 once-through cycle which has better fuel resource utilization than the conventional UO 2 cycle employed in current design PWRs. This fuel cycle uses more in-core batches and a higher discharge exposure than current PWR fuel management schemes. The proposed cycle is not optimal in a mathematical sense, however, since additional resource savings can be obtained if the discharge exposure is extended to even higher values and the number of in-core fuel batches is increased further. The present cycle was selected as ''optimal'' based on the assumption that it can be achieved with only an extension of fuel design technology and can therefore be deployed in a relatively short time frame. In the longer term, modification to reactor geometry as well as further extensions of discharge burnup might be considered to realize additional reduction in uranium resource requirements. The data contained in this paper has been developed by an ongoing program which at the present time is only 50% complete. The data presented here should therefore be considered preliminary and will be updated in the future as required

  3. Daily disposable contact lens prescribing around the world.

    Science.gov (United States)

    Efron, Nathan; Morgan, Philip B; Helland, Magne; Itoi, Motozumi; Jones, Deborah; Nichols, Jason J; van der Worp, Eef; Woods, Craig A

    2010-10-01

    Daily disposable contact lenses were introduced into the market 16 years ago. Data that we have gathered from annual contact lens fitting surveys conducted in Australia, Canada, Japan, The Netherlands, Norway, the UK and the USA between 2000 and 2008 indicates an overall increase in daily disposable lens fitting during this period. Daily disposable lenses are especially popular in Japan, Norway and the UK. There is a trend for these lenses to be fitted on a part-time basis. Males are over-represented in daily disposable lens fitting-a trend that is especially evident in Canada. Daily disposable lens wearers are about two years younger than wearers of reusable lenses in Japan and The Netherlands. The convenience and health benefits of daily disposable lenses are expected to fuel continued growth in this sector. Copyright (c) 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  4. 1 CFR 5.6 - Daily publication.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Daily publication. 5.6 Section 5.6 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.6 Daily publication. There shall be an edition of the Federal Register published for each official Federal working day...

  5. Daily Self-Disclosure and Sleep in Couples

    Science.gov (United States)

    Kane, Heidi S.; Slatcher, Richard B.; Reynolds, Bridget M.; Repetti, Rena L.; Robles, Theodore F.

    2014-01-01

    Objective An emerging literature provides evidence for the association between romantic relationship quality and sleep, an important factor in health and well-being. However, we still know very little about the specific relationship processes that affect sleep behavior. Therefore, the goal of this study was to examine how self-disclosure, an important relational process linked to intimacy, relationship satisfaction and health, is associated with sleep behavior. Method As part of a larger study of family processes, wives (n=46) and husbands (n=38) from 46 cohabiting families completed 56 days of daily diaries. Spouses completed evening diaries assessing daily self-disclosure, relationship satisfaction, and mood and morning diaries assessing the prior night's sleep. Multilevel modeling was used to explore the effects of both daily variation in and average levels across the 56 days of self-disclosure on sleep. Results Daily variation in self-disclosure predicted sleep outcomes for wives, but not for husbands. On days when wives self-disclosed more to their spouses than their average level, their subjective sleep quality and sleep efficiency that night improved. Furthermore, daily self-disclosure buffered the negative effect of daily negative mood on sleep latency for wives, but not husbands. In contrast, higher average levels of self-disclosure predicted less waking during the night for husbands, but not for wives. Conclusion The association between self-disclosure and sleep is one mechanism by which daily relationship functioning may influence health and well-being. Gender may play a role in how self-disclosure is associated with sleep. PMID:25068453

  6. ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases.

    Science.gov (United States)

    Kline, C Leah B; Van den Heuvel, A Pieter J; Allen, Joshua E; Prabhu, Varun V; Dicker, David T; El-Deiry, Wafik S

    2016-02-16

    ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases Akt and ERK and induces cell death through the proapoptotic protein TRAIL. ONC201 is currently in early-phase clinical testing for various malignancies. We found through gene expression and protein analyses that ONC201 triggered an increase in TRAIL abundance and cell death through an integrated stress response (ISR) involving the transcription factor ATF4, the transactivator CHOP, and the TRAIL receptor DR5. ATF4 was not activated in ONC201-resistant cancer cells, and in ONC201-sensitive cells, knockdown of ATF4 or CHOP partially abrogated ONC201-induced cytotoxicity and diminished the ONC201-stimulated increase in DR5 abundance. The activation of ATF4 in response to ONC201 required the kinases HRI and PKR, which phosphorylate and activate the translation initiation factor eIF2α. ONC201 rapidly triggered cell cycle arrest, which was associated with decreased abundance of cyclin D1, decreased activity of the kinase complex mTORC1, and dephosphorylation of the retinoblastoma (Rb) protein. The abundance of X-linked inhibitor of apoptosis protein (XIAP) negatively correlated with the extent of apoptosis in response to ONC201. These effects of ONC201 were independent of whether cancer cells had normal or mutant p53. Thus, ONC201 induces cell death through the coordinated induction of TRAIL by an ISR pathway. Copyright © 2016, American Association for the Advancement of Science.

  7. Cancer stem cell-related gene expression as a potential biomarker of response for first-in-class imipridone ONC201 in solid tumors.

    Directory of Open Access Journals (Sweden)

    Varun V Prabhu

    Full Text Available Cancer stem cells (CSCs correlate with recurrence, metastasis and poor survival in clinical studies. Encouraging results from clinical trials of CSC inhibitors have further validated CSCs as therapeutic targets. ONC201 is a first-in-class small molecule imipridone in Phase I/II clinical trials for advanced cancer. We have previously shown that ONC201 targets self-renewing, chemotherapy-resistant colorectal CSCs via Akt/ERK inhibition and DR5/TRAIL induction. In this study, we demonstrate that the anti-CSC effects of ONC201 involve early changes in stem cell-related gene expression prior to tumor cell death induction. A targeted network analysis of gene expression profiles in colorectal cancer cells revealed that ONC201 downregulates stem cell pathways such as Wnt signaling and modulates genes (ID1, ID2, ID3 and ALDH7A1 known to regulate self-renewal in colorectal, prostate cancer and glioblastoma. ONC201-mediated changes in CSC-related gene expression were validated at the RNA and protein level for each tumor type. Accordingly, we observed inhibition of self-renewal and CSC markers in prostate cancer cell lines and patient-derived glioblastoma cells upon ONC201 treatment. Interestingly, ONC201-mediated CSC depletion does not occur in colorectal cancer cells with acquired resistance to ONC201. Finally, we observed that basal expression of CSC-related genes (ID1, CD44, HES7 and TCF3 significantly correlate with ONC201 efficacy in >1000 cancer cell lines and combining the expression of multiple genes leads to a stronger overall prediction. These proof-of-concept studies provide a rationale for testing CSC expression at the RNA and protein level as a predictive and pharmacodynamic biomarker of ONC201 response in ongoing clinical studies.

  8. Cancer stem cell-related gene expression as a potential biomarker of response for first-in-class imipridone ONC201 in solid tumors.

    Science.gov (United States)

    Prabhu, Varun V; Lulla, Amriti R; Madhukar, Neel S; Ralff, Marie D; Zhao, Dan; Kline, Christina Leah B; Van den Heuvel, A Pieter J; Lev, Avital; Garnett, Mathew J; McDermott, Ultan; Benes, Cyril H; Batchelor, Tracy T; Chi, Andrew S; Elemento, Olivier; Allen, Joshua E; El-Deiry, Wafik S

    2017-01-01

    Cancer stem cells (CSCs) correlate with recurrence, metastasis and poor survival in clinical studies. Encouraging results from clinical trials of CSC inhibitors have further validated CSCs as therapeutic targets. ONC201 is a first-in-class small molecule imipridone in Phase I/II clinical trials for advanced cancer. We have previously shown that ONC201 targets self-renewing, chemotherapy-resistant colorectal CSCs via Akt/ERK inhibition and DR5/TRAIL induction. In this study, we demonstrate that the anti-CSC effects of ONC201 involve early changes in stem cell-related gene expression prior to tumor cell death induction. A targeted network analysis of gene expression profiles in colorectal cancer cells revealed that ONC201 downregulates stem cell pathways such as Wnt signaling and modulates genes (ID1, ID2, ID3 and ALDH7A1) known to regulate self-renewal in colorectal, prostate cancer and glioblastoma. ONC201-mediated changes in CSC-related gene expression were validated at the RNA and protein level for each tumor type. Accordingly, we observed inhibition of self-renewal and CSC markers in prostate cancer cell lines and patient-derived glioblastoma cells upon ONC201 treatment. Interestingly, ONC201-mediated CSC depletion does not occur in colorectal cancer cells with acquired resistance to ONC201. Finally, we observed that basal expression of CSC-related genes (ID1, CD44, HES7 and TCF3) significantly correlate with ONC201 efficacy in >1000 cancer cell lines and combining the expression of multiple genes leads to a stronger overall prediction. These proof-of-concept studies provide a rationale for testing CSC expression at the RNA and protein level as a predictive and pharmacodynamic biomarker of ONC201 response in ongoing clinical studies.

  9. 20 CFR 330.3 - Daily rate of compensation.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Daily rate of compensation. 330.3 Section 330.3 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD UNEMPLOYMENT INSURANCE ACT DETERMINATION OF DAILY BENEFIT RATES § 330.3 Daily rate of compensation. (a) Definition. An...

  10. Deposition of intranasal glucocorticoids--preliminary study.

    Science.gov (United States)

    Rapiejko, Piotr; Sosnowski, Tomasz R; Sova, Jarosław; Jurkiewicz, Dariusz

    2015-01-01

    Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency of particular medications proven by therapeutic index may result from differences in composition of particular formulations as well as from diverse deposition in nasal cavities. Intranasal formulations of glucocorticoids differ in volume of a single dose in addition to variety in density, viscosity and dispenser nozzle structure. The aim of this report was to analyze the deposition of most often used intranasal glucocorticoids in the nasal cavity and assessment of the usefulness of a nose model from a 3D printer reflecting anatomical features of a concrete patient. Three newest and most often used in Poland intranasal glucocorticoids were chosen to analysis; mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Droplet size distribution obtained from the tested formulations was determined by use of a laser aerosol spectrometer Spraytec (Malvern Instruments, UK). The model of the nasal cavity was obtained using a 3D printer. The printout was based upon a tridimensional reconstruction of nasal cavity created on the basis of digital processing of computed tomography of paranasal sinuses. The deposition of examined medications was established by a method of visualization combined with image analysis using commercial substance which colored itself intensively under the influence of water being the dominant ingredient of all tested preparations. On the basis of obtained results regions of dominating deposition of droplets of intranasal medication on the wall and septum of the nasal cavity were compared. Droplet size of aerosol of tested intranasal medications typically lies within the range of 25-150 µm. All tested medications deposited mainly on the anterior part of inferior turbinate. FP preparation deposited also on the anterior part of the middle nasal turbinate, marginally embracing a fragment of the central part of this

  11. V-Go Insulin Delivery System Versus Multiple Daily Insulin Injections for Patients With Uncontrolled Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Winter, Abigail; Lintner, Michaela; Knezevich, Emily

    2015-04-21

    Type 2 diabetes mellitus affects over 29.1 million Americans, diagnosed and undiagnosed. Achieving and maintaining glycemic control for these patients is of extreme importance when working to prevent complications and improve quality of life for patients. The V-Go is a newly developed insulin delivery system. The push of a button inserts a needle into the patient once daily and remains attached for 24 hours. The V-Go is designed to release a set basal rate throughout the day, while allowing patients to provide up to 36 units of on-demand bolus insulin with the manual click of 2 buttons. It is a spring-loaded device filled daily with rapid-acting insulin that runs without the use of batteries or computer software. The main objective of this prospective active comparator study was to observe the A1C lowering effects of multiple daily insulin injections (MDII) versus the use of the V-Go insulin delivery system for patients with uncontrolled type 2 diabetes mellitus over a 3-month period. In addition, the effect on insulin requirement for these patients was assessed with secondary comparisons of weight, blood pressure, prevalence of hypoglycemic events, and quality of life before and after 3 months of intensified insulin therapy with regular monitoring by a clinical pharmacist at an internal medicine clinic. The average A1C lowering experienced by the 3 patients in the V-Go group was 1.5%, while the average A1C change in the 3 patients in the MDII group was an increase of 0.2%. All patients in the V-Go group experienced a decrease in insulin total daily dose (TDD), with an average decrease of 26.3 units. All patients in the MDII group experienced an increase in insulin TDD with an average of 15 units daily to achieve therapeutic goals individualized for each patient. All patients who underwent intensification of insulin therapy experienced an increase in subjective quality of life (QOL) as determined using the Diabetes-39 (D-39) questionnaire, though QOL results lacked

  12. 'Once through' cycles in the pebble bed HTR

    International Nuclear Information System (INIS)

    Teuchert, E.

    1977-12-01

    In the pebble bed HTR the 'Once Through' cycles achieve a favorable conservation of uranium resources due to their high burnup and due to the relatively low fissile inventory. A detailed study is given for cycles with highly enriched uranium and thorium, 20% enriched uranium and thorium, and for the low (approximately 8%) enriched cycle. The recommended cycle is based on the known THTR fuel element in the Th/U (93%) cycle. The variant with separate Seed elements and Breed elements presents the best pioneer in view of later recycling and thermal breeding. The minimum proliferation risk is achieved in the Th/U (20%) cycle basing on the fuel element type of the AVR, due to the low amount and high denaturization of the disloaded plutonium. (orig.) [de

  13. Daily Stressors in Primary Education Students

    Science.gov (United States)

    Fernández-Baena, F. Javier; Trianes, María V.; Escobar, Milagros; Blanca, María J.; Muñoz, Ángela M.

    2015-01-01

    Daily stress can have a bearing on children's emotional and academic development. This study aimed to assess daily stressors and to determine their prevalence among primary education students, taking into account their gender, academic year, social adaptation, and the school location. A sample of 7,354 Spanish schoolchildren aged between 6 and 13…

  14. 23 CFR 661.23 - How will a bridge project be programmed for funding once eligibility has been determined?

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false How will a bridge project be programmed for funding once... bridge project be programmed for funding once eligibility has been determined? (a) All projects will be... time, the project will be acknowledged as either BIA and Tribally owned, or non-BIA owned and placed in...

  15. The effect of personality on daily life emotional processes.

    Science.gov (United States)

    Komulainen, Emma; Meskanen, Katarina; Lipsanen, Jari; Lahti, Jari Marko; Jylhä, Pekka; Melartin, Tarja; Wichers, Marieke; Isometsä, Erkki; Ekelund, Jesper

    2014-01-01

    Personality features are associated with individual differences in daily emotional life, such as negative and positive affectivity, affect variability and affect reactivity. The existing literature is somewhat mixed and inconclusive about the nature of these associations. The aim of this study was to shed light on what personality features represent in daily life by investigating the effect of the Five Factor traits on different daily emotional processes using an ecologically valid method. The Experience Sampling Method was used to collect repeated reports of daily affect and experiences from 104 healthy university students during one week of their normal lives. Personality traits of the Five Factor model were assessed using NEO Five Factor Inventory. Hierarchical linear modeling was used to analyze the effect of the personality traits on daily emotional processes. Neuroticism predicted higher negative and lower positive affect, higher affect variability, more negative subjective evaluations of daily incidents, and higher reactivity to stressors. Conscientiousness, by contrast, predicted lower average level, variability, and reactivity of negative affect. Agreeableness was associated with higher positive and lower negative affect, lower variability of sadness, and more positive subjective evaluations of daily incidents. Extraversion predicted higher positive affect and more positive subjective evaluations of daily activities. Openness had no effect on average level of affect, but predicted higher reactivity to daily stressors. The results show that the personality features independently predict different aspects of daily emotional processes. Neuroticism was associated with all of the processes. Identifying these processes can help us to better understand individual differences in daily emotional life.

  16. Development of chronic daily headache : A clinical study

    NARCIS (Netherlands)

    Spierings, E.L.H.; Schroevers, M.; Honkoop, P.C.; Sorbi, M.

    1998-01-01

    We studied the development of chronic daily headache in 258 headache practice patients, 50 men and 208 women. Chronic daily headache was defined as headaches occurring at least 5 days per week for at least 1 year. Twenty-two percent of the patients had daily headaches from the onset, and 78%

  17. Elemental constituent of food and the daily intake

    International Nuclear Information System (INIS)

    Suzuki, Kazumasa

    1976-01-01

    Constituent of element in foods and it's daily intake was discussed. In tables were shown instances of analysed values of major elements in Japanese foods, daily dietary intake of 8 elements in Japan (analysed value of total diet and estimated amounts of daily dietary intake of 32 elements. (J.P.N.)

  18. NOAA Daily Optimum Interpolation Sea Surface Temperature

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA 1/4° daily Optimum Interpolation Sea Surface Temperature (or daily OISST) is an analysis constructed by combining observations from different platforms...

  19. An ontology-based nurse call management system (oNCS) with probabilistic priority assessment

    Science.gov (United States)

    2011-01-01

    Background The current, place-oriented nurse call systems are very static. A patient can only make calls with a button which is fixed to a wall of a room. Moreover, the system does not take into account various factors specific to a situation. In the future, there will be an evolution to a mobile button for each patient so that they can walk around freely and still make calls. The system would become person-oriented and the available context information should be taken into account to assign the correct nurse to a call. The aim of this research is (1) the design of a software platform that supports the transition to mobile and wireless nurse call buttons in hospitals and residential care and (2) the design of a sophisticated nurse call algorithm. This algorithm dynamically adapts to the situation at hand by taking the profile information of staff members and patients into account. Additionally, the priority of a call probabilistically depends on the risk factors, assigned to a patient. Methods The ontology-based Nurse Call System (oNCS) was developed as an extension of a Context-Aware Service Platform. An ontology is used to manage the profile information. Rules implement the novel nurse call algorithm that takes all this information into account. Probabilistic reasoning algorithms are designed to determine the priority of a call based on the risk factors of the patient. Results The oNCS system is evaluated through a prototype implementation and simulations, based on a detailed dataset obtained from Ghent University Hospital. The arrival times of nurses at the location of a call, the workload distribution of calls amongst nurses and the assignment of priorities to calls are compared for the oNCS system and the current, place-oriented nurse call system. Additionally, the performance of the system is discussed. Conclusions The execution time of the nurse call algorithm is on average 50.333 ms. Moreover, the oNCS system significantly improves the assignment of nurses

  20. An ontology-based nurse call management system (oNCS with probabilistic priority assessment

    Directory of Open Access Journals (Sweden)

    Verhoeve Piet

    2011-02-01

    Full Text Available Abstract Background The current, place-oriented nurse call systems are very static. A patient can only make calls with a button which is fixed to a wall of a room. Moreover, the system does not take into account various factors specific to a situation. In the future, there will be an evolution to a mobile button for each patient so that they can walk around freely and still make calls. The system would become person-oriented and the available context information should be taken into account to assign the correct nurse to a call. The aim of this research is (1 the design of a software platform that supports the transition to mobile and wireless nurse call buttons in hospitals and residential care and (2 the design of a sophisticated nurse call algorithm. This algorithm dynamically adapts to the situation at hand by taking the profile information of staff members and patients into account. Additionally, the priority of a call probabilistically depends on the risk factors, assigned to a patient. Methods The ontology-based Nurse Call System (oNCS was developed as an extension of a Context-Aware Service Platform. An ontology is used to manage the profile information. Rules implement the novel nurse call algorithm that takes all this information into account. Probabilistic reasoning algorithms are designed to determine the priority of a call based on the risk factors of the patient. Results The oNCS system is evaluated through a prototype implementation and simulations, based on a detailed dataset obtained from Ghent University Hospital. The arrival times of nurses at the location of a call, the workload distribution of calls amongst nurses and the assignment of priorities to calls are compared for the oNCS system and the current, place-oriented nurse call system. Additionally, the performance of the system is discussed. Conclusions The execution time of the nurse call algorithm is on average 50.333 ms. Moreover, the oNCS system significantly improves

  1. 1 CFR 6.1 - Index to daily issues.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Index to daily issues. 6.1 Section 6.1 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER INDEXES AND ANCILLARIES § 6.1 Index to daily issues. Each daily issue of the Federal Register shall be appropriately indexed. ...

  2. An assessment of once-through homogeneous thorium fuel economics for light water reactors

    International Nuclear Information System (INIS)

    Joo, Hyung Kook; Noh, Jae Man; Yoo, Jae Woon

    2001-01-01

    The fuel economics of an once-through homogeneous thorium fuel concept for PWR was assessed by doing a detailed core analysis. In addition to this, the fuel economics assessment was also performed for two other ways enhancing the economic potential of thorium fuel; thorium utilization in the mixed core with uranium fuel assembly and Duplex thorium fuel concepts. As a results of fuel economics assessment, the thorium fuel cycle does not show any economic incentives in preference to uranium fuel cycle under the 18-months fuel cycle for PWR. However, the utilization of thorium is the mixed core with uranium fuel assembly and Duplex thorium fuel cycle and show superior fuel economics to uranium fuel under the longer fuel cycle scheme. The economic potential of once-through thorium fuel cycle is expected to be increased further by utilizing the Duplex thorium fuel in the mixed core with uranium fuel assembly

  3. Nonclinical safety and pharmacokinetics of Miglyol 812: A medium chain triglyceride in exenatide once weekly suspension.

    Science.gov (United States)

    Buss, Nicholas; Ryan, Patricia; Baughman, Todd; Roy, Denis; Patterson, Claire; Gordon, Carolyn; Dixit, Rakesh

    2018-05-28

    Exenatide, a glucagon-like peptide-1 receptor agonist was originally developed as either a twice daily or once weekly injectable therapeutic for patients with type 2 diabetes. Exenatide QW suspension was developed for use with an autoinjector device, in which the microspheres are suspended in Miglyol 812, a mixture of medium chain triglycerides (MCTs). MCTs are a class of lipids whose fatty acid chains contain from six to 12 carbon atoms (medium chain fatty acids or MCFAs). While MCTs are edible oils present in many foods, including foodstuffs containing coconut and palm kernel oils, limited information is available regarding the oral and subcutaneous bioavailability of MCTs as well as safety following subcutaneous injection. These studies were designed to investigate the non-clinical pharmacokinetics and safety of MCTs. In a single dose pharmacokinetic study, MCFAs were rapidly detected in the plasma of rats following oral administration of either Miglyol 812 or tricaprylin at doses of 10 or 9.48 g kg -1 , respectively. Following subcutaneous dosing with Miglyol 812, MCFAs were rapidly absorbed with a similar profile to that following oral dosing. Furthermore, the toxicity of Miglyol 812 alone was evaluated in a 3 month repeat dose toxicology studies in cynomolgus monkeys. In this study, weekly subcutaneous doses of 0.15 g kg -1 did not elicit any treatment-related effects in cynomolgus monkeys. In conclusion, these studies alongside the available literature data show that Miglyol 812 is a safe excipient for use in subcutaneously administered therapeutics. Copyright © 2018 John Wiley & Sons, Ltd.

  4. Impact of gastroesophageal reflux disease on work absenteeism, presenteeism and productivity in daily life: a European observational study.

    Science.gov (United States)

    Gisbert, Javier P; Cooper, Alun; Karagiannis, Dimitrios; Hatlebakk, Jan; Agréus, Lars; Jablonowski, Helmut; Nuevo, Javier

    2009-10-16

    The RANGE (Retrospective ANalysis of GastroEsophageal reflux disease [GERD]) study assessed differences among patients consulting a primary care physician due to GERD-related reasons in terms of: symptoms, diagnosis and management, response to treatment, and effects on productivity, costs and health-related quality of life. This subanalysis of RANGE determined the impact of GERD on productivity in work and daily life. RANGE was conducted at 134 primary care sites across six European countries (Germany, Greece, Norway, Spain, Sweden and the UK). All subjects (aged >or=18 years) who consulted with their primary care physician over a 4-month identification period were screened retrospectively, and those consulting at least once for GERD-related reasons were identified (index visit). From this population, a random sample was selected to enter the study and attended a follow-up appointment, during which the impact of GERD on productivity while working (absenteeism and presenteeism) and in daily life was evaluated using the self-reported Work Productivity and Activity Impairment Questionnaire for patients with GERD (WPAI-GERD). Overall, 373,610 subjects consulted with their primary care physician over the 4-month identification period, 12,815 for GERD-related reasons (3.4%); 2678 randomly selected patients attended the follow-up appointment. Average absenteeism due to GERD was highest in Germany (3.2 hours/week) and lowest in the UK (0.4 hours/week), with an average of up to 6.7 additional hours/week lost due to presenteeism in Norway. The average monetary impact of GERD-related work absenteeism and presenteeism were substantial in all countries (from euro55/week per employed patient in the UK to euro273/patient in Sweden). Reductions in productivity in daily life of up to 26% were observed across the European countries. GERD places a significant burden on primary care patients, in terms of work absenteeism and presenteeism and in daily life. The resulting costs to the

  5. Cystic Fibrosis-Related Diabetes (CFRD): Daily Management

    Science.gov (United States)

    Cystic Fibrosis-Related Diabetes (CFRD): Daily Management September 20, 2011 This Web cast is supported by an unrestricted ... Moran, MD Professor, Pediatric Endocrinology University of Minnesota Cystic Fibrosis-Related Diabetes (CFRD): Daily Management September 20, 2011 ...

  6. The Effects of Employment Status and Daily Stressors on Time Spent on Daily Household Chores in Middle-Aged and Older Adults

    Science.gov (United States)

    Wong, Jen D.; Almeida, David M.

    2013-01-01

    Purpose of the study: This study examines how employment status (worker vs. retiree) and life course influences (age, gender, and marital status) are associated with time spent on daily household chores. Second, this study assesses whether the associations between daily stressors and time spent on daily household chores differ as a function of…

  7. Modeling and simulation of once-through steam generator of casing pipes

    International Nuclear Information System (INIS)

    Niu Guanglin; Fu Mingyu; Yan Changqi; Nan Jingfu

    2009-01-01

    Adynamic model about the double casing pipes structure of double-face heat transfer is accepted in new type once-through steam generator (OTSG) is established. The model,which can be applied to any steady and dynamic conditions of OSTG in different flowing and heat transferring characteristic,is developed. It provides the bases for the design and operation of control system, analysis and treatment of abnormal conditions and faults, and development of operation rules. (authors)

  8. Daily self-disclosure and sleep in couples.

    Science.gov (United States)

    Kane, Heidi S; Slatcher, Richard B; Reynolds, Bridget M; Repetti, Rena L; Robles, Theodore F

    2014-08-01

    An emerging literature provides evidence for the association between romantic relationship quality and sleep, an important factor in health and well-being. However, we still know very little about the specific relationship processes that affect sleep behavior. Therefore, the goal of this study was to examine how self-disclosure, an important relational process linked to intimacy, relationship satisfaction, and health, is associated with sleep behavior. As part of a larger study of family processes, wives (n = 46) and husbands (n = 38) from 46 cohabiting families completed 56 days of daily diaries. Spouses completed evening diaries assessing daily self-disclosure, relationship satisfaction, and mood and morning diaries assessing the prior night's sleep. Multilevel modeling was used to explore the effects of both daily variation in and average levels across the 56 days of self-disclosure on sleep. Daily variation in self-disclosure predicted sleep outcomes for wives, but not for husbands. On days when wives self-disclosed more to their spouses than their average level, their subjective sleep quality and sleep efficiency that night improved. Furthermore, daily self-disclosure buffered the effect of high negative mood on sleep latency for wives, but not husbands. In contrast, higher average levels of self-disclosure predicted less waking during the night for husbands, but not for wives. The association between self-disclosure and sleep is one mechanism by which daily relationship functioning may influence health and well-being. Gender may play a role in how self-disclosure is associated with sleep.

  9. High prevalence of daily and multi-site pain

    DEFF Research Database (Denmark)

    Rathleff, Michael Skovdal; Roos, Ewa M.; Olesen, Jens Lykkegaard

    2013-01-01

    Daily pain and multi-site pain are both associated with reduction in work ability and health-related quality of life (HRQoL) among adults. However, no population-based studies have yet investigated the prevalence of daily and multi-site pain among adolescents and how these are associated...... with respondent characteristics. The purpose of this study was to investigate the prevalence of self-reported daily and multi-site pain among adolescents aged 12--19 years and associations of almost daily pain and multi-site pain with respondent characteristics (sex, age, body mass index (BMI), HRQoL and sports...

  10. A fuzzy recommendation system for daily water intake

    Directory of Open Access Journals (Sweden)

    Bin Dai

    2016-05-01

    Full Text Available Water is one of the most important constituents of the human body. Daily consumption of water is thus necessary to protect human health. Daily water consumption is related to several factors such as age, ambient temperature, and degree of physical activity. These factors are generally difficult to express with exact numerical values. The main objective of this article is to build a daily water intake recommendation system using fuzzy methods. This system will use age, physical activity, and ambient temperature as the input factors and daily water intake values as the output factor. The reasoning mechanism of the fuzzy system can calculate the recommended value of daily water intake. Finally, the system will compare the actual recommended values with our system to determine the usefulness. The experimental results show that this recommendation system is effective in actual application.

  11. Small-Molecule ONC201/TIC10 Targets Chemotherapy-Resistant Colorectal Cancer Stem-like Cells in an Akt/Foxo3a/TRAIL-Dependent Manner.

    Science.gov (United States)

    Prabhu, Varun V; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S

    2015-04-01

    Self-renewing colorectal cancer stem/progenitor cells (CSC) contribute to tumor maintenance and resistance to therapy. Therapeutic targeting of CSCs could improve treatment response and prolong patient survival. ONC201/TIC10 is a first-in-class antitumor agent that induces TRAIL pathway-mediated cell death in cancer cells without observed toxicity. We have previously described that ONC201/TIC10 exposure leads to transcriptional induction of the TRAIL gene via transcription factor Foxo3a, which is activated by dual inactivation of Akt and ERK. The Akt and ERK pathways serve as important targets in CSCs. Foxo3a is a key mediator of Akt and ERK-mediated CSC regulation. We hypothesized that the potent antitumor effect of ONC201/TIC10 in colorectal cancer involves targeting CSCs and bulk tumor cells. ONC201/TIC10 depletes CD133(+), CD44(+), and Aldefluor(+) cells in vitro and in vivo. TIC10 significantly inhibits colonosphere formation of unsorted and sorted 5-fluorouracil-resistant CSCs. ONC201/TIC10 significantly reduces CSC-initiated xenograft tumor growth in mice and prevents the passage of these tumors. ONC201/TIC10 treatment also decreased xenograft tumor initiation and was superior to 5-fluorouracil treatment. Thus, ONC201/TIC10 inhibits CSC self-renewal in vitro and in vivo. ONC201/TIC10 inhibits Akt and ERK, consequently activating Foxo3a and significantly induces cell surface TRAIL and DR5 expression in both CSCs and non-CSCs. ONC201/TIC10-mediated anti-CSC effect is significantly blocked by the TRAIL sequestering antibody RIK-2. Overexpression of Akt, DR5 knockdown, and Foxo3a knockdown rescues ONC201/TIC10-mediated depletion of CD44(+) cells and colonosphere inhibition. In conclusion, ONC201/TIC10 is a promising agent for colorectal cancer therapy that targets both non-CSCs and CSCs in an Akt-Foxo3a-TRAIL-dependent manner. ©2015 American Association for Cancer Research.

  12. Small molecule ONC201/TIC10 targets chemotherapy-resistant colorectal cancer stem-like cells in an Akt/Foxo3a/TRAIL-dependent manner

    Science.gov (United States)

    Prabhu, Varun V.; Allen, Joshua E.; Dicker, David T.; El-Deiry, Wafik S.

    2015-01-01

    Self-renewing colorectal cancer stem/progenitor cells (CSCs) contribute to tumor maintenance and resistance to therapy. Therapeutic targeting of CSCs could improve treatment response and prolong patient survival. ONC201/TIC10 is a first-in-class anti-tumor agent that induces TRAIL pathway mediated cell death in cancer cells without observed toxicity. We have previously described that ONC201/TIC10 exposure leads to transcriptional induction of the TRAIL gene via transcription factor Foxo3a, which is activated by dual inactivation of Akt and ERK. The Akt and ERK pathways serve as important targets in CSCs. Foxo3a is a key mediator of Akt and ERK-mediated CSC regulation. We hypothesized that the potent anti-tumor effect of ONC201/TIC10 in colorectal cancer involves targeting CSCs and bulk tumor cells. ONC201/TIC10 depletes CD133(+), CD44(+) and Aldefluor(+) cells in vitro and in vivo. TIC10 significantly inhibits colonosphere formation of unsorted and sorted 5-Fluorouracil-resistant CSCs. ONC201/TIC10 significantly reduces CSC-initiated xenograft tumor growth in mice and prevents the passage of these tumors. ONC201/TIC10 treatment also decreased xenograft tumor initiation and was superior to 5-Fluorouracil treatment. Thus, ONC201/TIC10 inhibits CSC self-renewal in vitro and in vivo. ONC201/TIC10 inhibits Akt and ERK, consequently activating Foxo3a and significantly induces cell surface TRAIL and DR5 expression in both CSCs and non-CSCs. ONC201/TIC10-mediated anti-CSC effect is significantly blocked by the TRAIL sequestering antibody RIK-2. Overexpression of Akt, DR5 knockdown and Foxo3a knockdown rescues ONC201/TIC10-mediated depletion of CD44(+) cells and colonosphere inhibition. In conclusion, ONC201/TIC10 is a promising agent for colorectal cancer therapy that targets both non-CSCs and CSCs in an Akt-Foxo3a-TRAIL-dependent manner. PMID:25712124

  13. Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

    Science.gov (United States)

    Stone, Ian S; Barnes, Neil C; James, Wai-Yee; Midwinter, Dawn; Boubertakh, Redha; Follows, Richard; John, Leonette; Petersen, Steffen E

    2016-04-01

    Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting β2-agonist fluticasone furoate/vilanterol 100/25 μg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P volume index and a 429 ml (P volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).

  14. Daily stress, presleep arousal, and sleep in healthy young women: a daily life computerized sleep diary and actigraphy study.

    Science.gov (United States)

    Winzeler, Katja; Voellmin, Annette; Schäfer, Valérie; Meyer, Andrea H; Cajochen, Christian; Wilhelm, Frank H; Bader, Klaus

    2014-03-01

    Our study aimed to further elucidate the mediating role of presleep arousal in the relationship between daily stress and sleep by investigating subjective sleep quality and actigraphy-assessed sleep efficiency (SE) on both within- and between-participant levels in a sample of healthy young women. Multilevel modeling was applied on electronically assessed data comprising 14 consecutive nights in 145 healthy young women to assess the relationship between daily stress, presleep (somatic and cognitive) arousal, and sleep on both levels between participants and within participants across days. Higher levels of daily stress were consistently and significantly associated with higher levels of somatic and cognitive arousal. Somatic arousal mediated the relationship between daily stress and worsened subjective sleep quality on the between-participant level, while cognitive arousal mediated the relationship between daily stress and worsened subjective sleep quality on the within-participants level. Unexpectedly, healthy young women showed higher SE following days with above-average stress with somatic arousal mediating this relationship. Our data corroborate the role of presleep arousal mediating the relationship between daily stress and subjective sleep quality. Interestingly this effect was restricted to somatic arousal being relevant on interindividual levels and cognitive arousal on intraindividual levels. For young and healthy individuals who experience high stress and arousal, well-established cognitive-behavioral techniques could be useful to regulate arousal and prevent worse subjective sleep quality. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Dayak and Their Daily Life

    Directory of Open Access Journals (Sweden)

    Hamid Darmadi

    2017-03-01

    Full Text Available This article titled "Dayak and Daily Life" This paper aims to reveal the Dayak and in their daily life. Dayak is a native of Borneo has its own characteristics. Dayak, divided into 405 sub-sub clans [1]. Each sub Dayak both Indonesia and Malaysia are identical. Dayak customs and culture comes from the word "Power" which means upstream, to refer to people who live in inland areas or in the interior of Borneo. In the arsenal of art and culture, Dayak has many similarities such as; saber, chopsticks, beliong, betang, cupai, renjung, empajang and others. Dayak indigenous religion is Kaharingan which is the original religion born of the cultural ancestors of the Dayaks. Most of the Dayak people still adhere to the belief of the existence of unseen objects in certain places such as rocks, large trees, planting gardens in the forest, lakes, pools, and others are believed to have "magical powers". Daily life of the Dayaks in general farming, farming. When will open farming land, farming they held ritual.

  16. Daily torpor and hibernation in birds and mammals

    Science.gov (United States)

    RUF, THOMAS; GEISER, FRITZ

    2014-01-01

    Many birds and mammals drastically reduce their energy expenditure during times of cold exposure, food shortage, or drought, by temporarily abandoning euthermia, i.e., the maintenance of high body temperatures. Traditionally, two different types of heterothermy, i.e., hypometabolic states associated with low body temperatures (torpor), have been distinguished: Daily torpor, which lasts less than 24 h and is accompanied by continued foraging, versus hibernation, with torpor bouts lasting consecutive days to several weeks in animals that usually do not forage but rely on energy stores, either food caches or body energy reserves. This classification of torpor types has been challenged however, suggesting that these phenotypes may merely represent the extremes in a continuum of traits. Here, we investigate whether variables of torpor in 214 species, 43 birds and 171 mammals form a continuum or a bimodal distribution. We use Gaussian-mixture cluster analysis as well as phylogenetically informed regressions to quantitatively assess the distinction between hibernation and daily torpor and to evaluate the impact of body mass and geographical distribution of species on torpor traits. Cluster analysis clearly confirmed the classical distinction between daily torpor and hibernation. Overall, heterothermic endotherms are small on average, but hibernators are significantly heavier than daily heterotherms and also are distributed at higher average latitudes (~35°) than daily heterotherms (~25°). Variables of torpor for an average 30-g heterotherm differed significantly between daily heterotherms and hibernators. Average maximum torpor bout duration was >30-fold longer, and mean torpor bout duration >25-fold longer in hibernators. Mean minimum body temperature differed by ~13°C, and the mean minimum torpor metabolic rate was ~35% of the BMR in daily heterotherms but only 6% of basal metabolic rate in hibernators. Consequently, our analysis strongly supports the view that

  17. Fuel utilization potential in light water reactors with once-through fuel irradiation (AWBA Development Program)

    International Nuclear Information System (INIS)

    Rampolla, D.S.; Conley, G.H.; Candelore, N.R.; Cowell, G.K.; Estes, G.P.; Flanery, B.K.; Duncombe, E.; Dunyak, J.; Satterwhite, D.G.

    1979-07-01

    Current commercial light water reactor cores operate without recylce of fuel, on a once-through fuel cycle. To help conserve the limited nuclear fuel resources, there is interest in increasing the energy yield and, hence, fuel utilization from once-through fuel irradiation. This report evaluates the potential increase in fuel utilization of light water reactor cores operating on a once-through cycle assuming 0.2% enrichment plant tails assay. This evaluation is based on a large number of survey calculations using techniques which were verified by more detailed calculations of several core concepts. It is concluded that the maximum fuel utilization which could be achieved by practical once-through pressurized light water reactor cores with either uranium or thorium is about 17 MWYth/ST U 3 O 8 (Megawatt Years Thermal per Short Ton of U 3 O 8 ). This is about 50% higher than that of current commercial light water reactor cores. Achievement of this increased fuel utilization would require average fuel burnup beyond 50,000 MWD/MT and incorporation of the following design features to reduce parasitic losses of neutrons: reflector blankets to utilize neutrons that would otherwise leak out of the core; fuel management practices in which a smaller fraction of the core is replaced at each refueling; and neutron economic reactivity control, such as movable fuel control rather than soluble boron control. For a hypothetical situation in which all neutron leakage and parasitic losses are eliminated and fuel depletion is not limited by design considerations, a maximum fuel utilization of about 20 MWYth/ST U 3 O 8 is calculated for either uranium or thorium. It is concluded that fuel utilization for comparable reactor designs is better with uranium fuel than with thorium fuel for average fuel depletions of 30,000 to 35,000 MWD/MT which are characteristic of present light water reactor cores

  18. christ as once for all sacrifice: a cultural reading of hebrews

    African Journals Online (AJOL)

    UV/UFS. . Rev. K.J. Pali, Department of Practical ..... of suffering from spiritual trauma which led to various psychological, .... lamps (Ex. 27:21), weekly placements of the breads (Lv. 24:5), and daily.

  19. Photoprotection in moisturizers and daily-care products.

    Science.gov (United States)

    Seite, S; Fourtanier, A; Rougier, A

    2010-10-01

    During usual daily activities, an appropriate protection against solar UV exposure should prevent clinical, cellular and molecular changes potentially leading to photoaging. In skin areas regularly exposed to sun, UV-damage is superimposed to tissue degeneration resulting from chronological aging. It is, therefore, important to know if moisturizers and daily-care products containing UVA absorbers combined with UVB ones are able to prevent these skin damages. This review will summarize clinical studies evaluating this topic. These studies demonstrate that broad-spectrum protection in moisturizers or daily-care products can prevent the "silent" sub-erythemal cumulative effects of UVR from inadvertent sun exposure.

  20. 35 years of Ambient Noise: Can We Evidence Daily to Climatic Relative Velocity Changes ?

    Science.gov (United States)

    Lecocq, T.; Pedersen, H.; Brenguier, F.; Stammler, K.

    2014-12-01

    The broadband Grafenberg array (Germany) has been installed in 1976 and, thanks to visionary scientists and network maintainers, the continuous data acquired has been preserved until today. Using state of the art pre-processing and cross-correlation techniques, we are able to extract cross-correlation functions (CCF) between sensor pairs. It has been shown recently that, provided enough computation power is available, there is no need to define a reference CCF to compare all days to. Indeed, one can compare each day to all days, computing the "all-doublet". The number of calculations becomes huge (N vs ref = N calculations, N vs N= N*N), but the result, once inverted, is way more stable because of the N observations per day. This analysis has been done on a parallelized version of MSNoise (http://msnoise.org), running on the VEGA cluster hosted at the Université Libre de Bruxelles (ULB, Belgium). Here, we present preliminary results of the analysis of two stations, GRA1 and GRA2, the first two stations installed in March 1976. The interferogram (observation of the CCF through time, see Figure) already shows interesting features in the ballistic wave shape, highly correlated to the seasons. A reasonably high correlation can still be seen outside the ballistic arrival, after +-5 second lag time. The lag times between 5 and 25 seconds are then used to compute the dv/v using the all-doublet method. We expect to evidence daily to seasonal, or even to longer period dv/v variations and/or noise source position changes using this method. Once done with 1 sensor pair, the full data of the Grafenberg array will be used to enhance the resolution even more.

  1. Simulation of daily rainfall through markov chain modeling

    International Nuclear Information System (INIS)

    Sadiq, N.

    2015-01-01

    Being an agricultural country, the inhabitants of dry land in cultivated areas mainly rely on the daily rainfall for watering their fields. A stochastic model based on first order Markov Chain was developed to simulate daily rainfall data for Multan, D. I. Khan, Nawabshah, Chilas and Barkhan for the period 1981-2010. Transitional probability matrices of first order Markov Chain was utilized to generate the daily rainfall occurrence while gamma distribution was used to generate the daily rainfall amount. In order to achieve the parametric values of mentioned cities, method of moments is used to estimate the shape and scale parameters which lead to synthetic sequence generation as per gamma distribution. In this study, unconditional and conditional probabilities of wet and dry days in sum with means and standard deviations are considered as the essential parameters for the simulated stochastic generation of daily rainfalls. It has been found that the computerized synthetic rainfall series concurred pretty well with the actual observed rainfall series. (author)

  2. 21 CFR 822.24 - What are my responsibilities once I am notified that I am required to conduct postmarket...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false What are my responsibilities once I am notified that I am required to conduct postmarket surveillance? 822.24 Section 822.24 Food and Drugs FOOD AND... SURVEILLANCE Responsibilities of Manufacturers § 822.24 What are my responsibilities once I am notified that I...

  3. Once more unto the breach managing information security in an uncertain world

    CERN Document Server

    Simmons, Andrea C

    2012-01-01

    In Once more unto the Breach, Andrea C Simmons speaks directly to information security managers and provides an insider's view of the role, offering priceless gems from her extensive experience and knowledge. Based on a typical year in the life of an information security manager, the book examines how the general principles can be applied to all situations and discusses the lessons learnt from a real project.

  4. ONC201 demonstrates anti-tumor effects in both triple negative and non-triple negative breast cancers through TRAIL-dependent and TRAIL-independent mechanisms

    OpenAIRE

    Ralff, Marie D.; Kline, Christina L.B.; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T.; Prabhu, Varun V.; Oster, Wolfgang; El-Deiry, Wafik S.

    2017-01-01

    Breast cancer is a major cause of cancer-related death. TRAIL has been of interest as a cancer therapeutic, but only a subset of triple negative breast cancers (TNBC) is sensitive to TRAIL. The small molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here we show that ONC201 is efficacious against both TNBC and non-TNBC cells (n=13). A subset of TNBC and non-TNBC cells succumb to ONC201-induced cell death. In 2/8 TNBC cell...

  5. 25 CFR 1000.73 - Once a Tribe/Consortium has been awarded a grant, may the Tribe/Consortium obtain information...

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Once a Tribe/Consortium has been awarded a grant, may the Tribe/Consortium obtain information from a non-BIA bureau? 1000.73 Section 1000.73 Indians OFFICE OF THE... § 1000.73 Once a Tribe/Consortium has been awarded a grant, may the Tribe/Consortium obtain information...

  6. CPD: The patient with daily headaches. | Maizels | South African ...

    African Journals Online (AJOL)

    The term "chronic daily headache" (CDH) describes a variety of headache types, of which chronic migraine is the most common. Daily headaches often are disabling and may be challenging to diagnose and treat. Medication overuse, or drug rebound headache, is the most treatable cause of refractory daily headache.

  7. Once-daily glycopyrronium bromide, a long-acting muscarinic antagonist, for chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli

    2012-01-01

    Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD). The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel...... long-acting muscarinic antagonist, in patients with COPD....

  8. New developments in the treatment of rosacea – role of once-daily ivermectin cream

    Directory of Open Access Journals (Sweden)

    Cardwell LA

    2016-03-01

    Full Text Available Leah A Cardwell,1 Hossein Alinia,1 Sara Moradi Tuchayi,1 Steven R Feldman,1–31Department of Dermatology, Center for Dermatology Research, 2Department of Pathology, 3Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Rosacea is a chronic dermatological disorder with a variety of clinical manifestations localized largely to the central face. The unclear etiology of rosacea fosters therapeutic difficulty; however, subtle clinical improvement with pharmacologic treatments of various drug categories suggests a multifactorial etiology of the disease. Factors that may contribute to disease pathogenesis include immune abnormality, vascular abnormality, neurogenic dysregulation, presence of cutaneous microorganisms, UV damage, and skin barrier dysfunction. The role of ivermectin in the treatment of rosacea may be as an anti-inflammatory and anti-parasitic agent targeting Demodex mites. In comparing topical ivermectin and metronidazole, ivermectin was more effective; this treatment modality boasted more improved quality of life, reduced lesion counts, and more favorable participant and physician assessment of disease severity. Patients who received ivermectin 1% cream had an acceptable safety profile. Ivermectin is efficacious in decreasing inflammatory lesion counts and erythema. Keywords: papulopustular rosacea, topical ivermectin, metronidazole, azelaic acid, topical

  9. Numerical simulation of dryout and post-dryout heat transfer in a straight-pipe once-through steam generator

    International Nuclear Information System (INIS)

    Shi, Jianxin; Sun, Baozhi; Han, Wenjing; Zhang, Guolei; Li, Yanjun; Yang, Longbin

    2016-01-01

    Highlights: • Two-fluid three-flow-field model is developed to predict dryout in steam generator. • The empirical correlation is used to correct dryout criterion. • The interactions between three-flow-fields and the wall are considered. • Dryout and post-dryout heat transfer mechanisms are discussed through the results. - Abstract: Accurately predicting dryout and post-dryout heat transfer characteristics is critical for proper design of once-through steam generators. This paper provides a reasonable and simple method for this prediction by introducing a two-fluid, three-flow-field mathematical model and improving the dryout criterion-critical quality, and conducts a numerical simulation of dryout and post-dryout heat transfer in a once-through steam generator to prove the model’s performance. The results show that the critical quality in a once-through steam generator is about 0.82, with the heat transfer capacity significantly reducing and the wall temperature sharply increasing in a non-linear form by approximately 30 K when dryout occurs. Part of the steam is superheated in the post-dryout region, resulting in a deviation from thermodynamic equilibrium between the vapor and liquid phases. Dryout and post-dryout heat transfer in the once-through steam generator operate between complete deviation from thermodynamic equilibrium and complete thermodynamic equilibrium. Therefore, the presence of droplets has a significant influence on the mass, momentum and energy transfer between the film and vapor phases.

  10. Studi Awal Desain Pebble Bed Reactor Berbasis Htr-pm Dengan Skema Resirkulasi Bahan Bakar Once-through-then-out

    OpenAIRE

    Setiadipura, Topan; Pane, Jupiter Sitorus; Zuhair, Zuhair

    2016-01-01

    STUDI AWAL DESAIN PEBBLE BED REACTOR BERBASIS HTR-PM DENGAN RESIRKULASI BAHAN BAKAR ONCE-THROUGH-THEN-OUT. Reaktor nuklir tipe pebble bed reactor (PBR) adalah salah satu reaktor canggih dengan fitur keselamatan pasif yang kuat. Pada desain tipe ini berpotensi untuk dilakukan kogenerasi yang bermanfaat untuk pengolahan berbagai mineral di berbagai pulau di Indonesia. Operasi PBR dapat lebih disederhanakan dengan menerapkan skema pengisian bahan bakar once-through-then-out (OTTO) dimana bahan b...

  11. A fuzzy recommendation system for daily water intake

    OpenAIRE

    Bin Dai; Rung-Ching Chen; Shun-Zhi Zhu; Chung-Yi Huang

    2016-01-01

    Water is one of the most important constituents of the human body. Daily consumption of water is thus necessary to protect human health. Daily water consumption is related to several factors such as age, ambient temperature, and degree of physical activity. These factors are generally difficult to express with exact numerical values. The main objective of this article is to build a daily water intake recommendation system using fuzzy methods. This system will use age, physical activity, and a...

  12. Once-through CANDU reactor models for the ORIGEN2 computer code

    International Nuclear Information System (INIS)

    Croff, A.G.; Bjerke, M.A.

    1980-11-01

    Reactor physics calculations have led to the development of two CANDU reactor models for the ORIGEN2 computer code. The model CANDUs are based on (1) the existing once-through fuel cycle with feed comprised of natural uranium and (2) a projected slightly enriched (1.2 wt % 235 U) fuel cycle. The reactor models are based on cross sections taken directly from the reactor physics codes. Descriptions of the reactor models, as well as values for the ORIGEN2 flux parameters THERM, RES, and FAST, are given

  13. Fuel-management simulations for once-through thorium fuel cycle in CANDU reactors

    International Nuclear Information System (INIS)

    Chan, P.S.W.; Boczar, P.G.; Ellis, R.J.; Ardeshiri, F.

    1999-01-01

    High neutron economy, on-power refuelling and a simple fuel bundle design result in unsurpassed fuel cycle flexibility for CANDU reactors. These features facilitate the introduction and exploitation of thorium fuel cycles in existing CANDU reactors in an evolutionary fashion. Detailed full-core fuel-management simulations concluded that a once-through thorium fuel cycle can be successfully implemented in an existing CANDU reactor without requiring major modifications. (author)

  14. Climate Prediction Center (CPC) US daily temperature analyses

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The U.S. daily temperature analyses are maps depicting various temperature quantities utilizing daily maximum and minimum temperature data across the US. Maps are...

  15. 19 CFR 159.35 - Certified daily rate.

    Science.gov (United States)

    2010-04-01

    ... TREASURY (CONTINUED) LIQUIDATION OF DUTIES Conversion of Foreign Currency § 159.35 Certified daily rate. The daily buying rate of foreign currency which is determined by the Federal Reserve Bank of New York and certified to the Secretary of the Treasury in accordance with 31 U.S.C. 5151(e) shall be used for...

  16. CDC WONDER: Daily Air Temperatures and Heat Index

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Daily Air Temperature and Heat Index data available on CDC WONDER are county-level daily average air temperatures and heat index measures spanning the years...

  17. Understanding Motivations to Adopt Once-a-Day Milking amongst New Zealand Dairy Farmers

    Science.gov (United States)

    Bewsell, D.; Clark, D. A.; Dalley, D. E.

    2008-01-01

    This paper reports the results of a study to understand why some New Zealand dairy farmers are changing from twice-a-day (TAD) to once-a-day (OAD) milking. Increasing herd size, unavailability of suitable labour and changing lifestyle expectations from farmers and their staff have led some to explore OAD milking as a means of alleviating these…

  18. Transmutation Capability of a Once-Through Molten-Salt and Other Transmuting Reactors

    International Nuclear Information System (INIS)

    Greenspan, E.; Lowenthal, M.; Barnes, D.; Kawasaki, D.; Kimball, D.; Matsumoto, H.; Sagara, H.; Vietez, E.R.

    2002-01-01

    A preliminary assessment is done of the transmutation characteristics of three reactor technologies: a multi-batch liquid metal (LM) cooled transmuter, a once-through molten-salt (MS) transmuter and a pebble bed (PB) transmuter. It was found that for the same fractional transmutation and same k eff drop with burnup (Δk effBU ), lead-bismuth offers smaller peak-to-average core power density, and it requires a smaller pumping power but a larger and heavier core than a sodium cooled transmuter. 99 Tc cannot effectively serve as a burnable absorber to reduce Δk effBU of LM transmuters. However, addition of thorium can greatly flatten k eff and almost double the fractional transmutation of the LWR spent fuel from ∼20% to ∼40%. If the 'once-through' MS transmuter is operated with continuous complete removal of fission products, it can achieve ∼85% fractional transmutation provided that the equilibrium concentration of actinides in the MS can reach 4 mole %. If the fission products are not actively removed, the fractional transmutation is reduced to ∼75%. The fractional transmutation of a PB transmuter can exceed 40%. More thorough analysis is required to better quantify the transmutation capability of the different transmuter technologies. (authors)

  19. Impact of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod: Subgroup analyses of the Fingolimod Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study.

    Science.gov (United States)

    Kremenchutzky, Marcelo; O'Connor, Paul; Hohlfeld, Reinhard; Zhang-Auberson, Lixin; von Rosenstiel, Philipp; Meng, Xiangyi; Grinspan, Augusto; Hashmonay, Ron; Kappos, Ludwig

    2014-05-01

    Fingolimod is a once-daily, oral sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing multiple sclerosis. This post-hoc analysis of phase 3 FREEDOMS data assessed whether the effects of fingolimod are consistent among subgroups of patients defined by prior treatment history. Annualized relapse rate and safety profile of treatment with fingolimod 0.5mg, 1.25mg, or placebo once-daily for 24 months were analyzed in 1272 relapsing multiple sclerosis patients, by subgroups based on disease-modifying therapy history (treatment-naive; prior interferon-β or glatiramer acetate), reason for discontinuation of prior disease-modifying therapy (unsatisfactory therapeutic response or adverse events), and prior disease-modifying therapy duration. Both fingolimod doses significantly reduced annualized relapse rate in patients that received prior interferon-β or glatiramer acetate, discontinued prior disease-modifying therapy owing to unsatisfactory therapeutic effect, were treatment-naive, or had prior disease-modifying therapy duration of >1-3 years (P≤0.0301 for all comparisons vs placebo). Fingolimod 1.25mg resulted in greater reductions in annualized relapse rate in patients that discontinued prior disease-modifying therapy for adverse events or had prior disease-modifying therapy duration of ≤1 year or >3 years (P≤0.0194 vs placebo). Fingolimod demonstrated similar efficacy in relapsing multiple sclerosis patients regardless of prior treatment history. Clinicaltrials.gov identifier: NCT00289978. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Daily Nigerian peak load forecasting using artificial neural network ...

    African Journals Online (AJOL)

    A daily peak load forecasting technique that uses artificial neural network with seasonal indices is presented in this paper. A neural network of relatively smaller size than the main prediction network is used to predict the daily peak load for a period of one year over which the actual daily load data are available using one ...

  1. Gender, Emotion Work, and Relationship Quality: A Daily Diary Study

    Science.gov (United States)

    Curran, Melissa A.; McDaniel, Brandon T.; Pollitt, Amanda M.; Totenhagen, Casey J.

    2015-01-01

    We use the gender relations perspective from feminist theorizing to investigate how gender and daily emotion work predict daily relationship quality in 74 couples (148 individuals in dating, cohabiting, or married relationships) primarily from the southwest U.S. Emotion work is characterized by activities that enhance others’ emotional well-being. We examined emotion work two ways: trait (individuals’ average levels) and state (individuals’ daily fluctuations). We examined actor and partner effects of emotion work and tested for gender differences. As outcome variables, we included six types of daily relationship quality: love, commitment, satisfaction, closeness, ambivalence, and conflict. This approach allowed us to predict three aspects of relationship quality: average levels, daily fluctuations, and volatility (overall daily variability across a week). Three patterns emerged. First, emotion work predicted relationship quality in this diverse set of couples. Second, gender differences were minimal for fixed effects: Trait and state emotion work predicted higher average scores on, and positive daily increases in, individuals’ own positive relationship quality and lower average ambivalence. Third, gender differences were more robust for volatility: For partner effects, having a partner who reported higher average emotion work predicted lower volatility in love, satisfaction, and closeness for women versus greater volatility in love and commitment for men. Neither gender nor emotion work predicted average levels, daily fluctuations, or volatility in conflict. We discuss implications and future directions pertaining to the unique role of gender in understanding the associations between daily emotion work and volatility in daily relationship quality for relational partners. PMID:26508808

  2. Efficacy and safety of once-weekly intravenous epoetin alfa in maintaining hemoglobin levels in hemodialysis patients.

    Science.gov (United States)

    Locatelli, Francesco; Villa, Giuseppe; Messa, Piergiorgio; Filippini, Armando; Cannella, Giuseppe; De Ferrari, Giacomo; Naso, Agostino; Rossi, Egidio; Formica, Marco; Lombardi, Luigi; Rotolo, Ugo; Conte, Feruccio

    2008-01-01

    Although an erythropoiesis-stimulating agent (ESA) is most frequently administered intravenously for treatment of anemia in patients with chronic kidney disease who are on dialysis, few studies have compared the efficacy of different intravenous (i.v.) dosing schedules. This multicenter, phase IIIb, open-label, controlled study randomized 289 stable hemodialysis patients to continue with conventional dosing of i.v. epoetin alfa or darbepoetin, or to switch to once-weekly i.v. epoetin alfa at the same cumulative weekly starting dose, to maintain hemoglobin levels at 11.0-13.0 g/dL, and within 1.0 g/dL of the baseline value. Hemoglobin levels and ESA doses were recorded every 4 weeks for 28 weeks. Hemoglobin levels fell significantly and ESA doses increased significantly between baseline and week 28 (mean of week 16-28 values) in the once-weekly epoetin alfa group, compared with the conventional treatment group (phemoglobin levels between the groups was 0.73 g/dL (greater than the threshold for therapeutic equivalence of 0.5 g/dL). The changes between groups from baseline was significant at all time points for hemoglobin levels (0.36, 0.46, 0.81, 0.87, 0.78, 0.62 and 0.49 g/dL) and from week 12 for ESA dose (718.5, 1,326.5, 1,732.0, 1,839.7 and 1,959.1 IU/week; p=0.005). Hemoglobin was maintained at the target level in 78% and 84% of patients on conventional dosing, and 67% and 64% of those on once-weekly epoetin alfa in the intention-to-treat (p=0.1) and per protocol (p=0.016) populations, respectively. This study did not show therapeutic equivalence of once-weekly i.v. epoetin alfa with conventional dosing regimens.

  3. The angular structure of ONC201, a TRAIL pathway-inducing compound, determines its potent anti-cancer activity.

    Science.gov (United States)

    Wagner, Jessica; Kline, Christina Leah; Pottorf, Richard S; Nallaganchu, Bhaskara Rao; Olson, Gary L; Dicker, David T; Allen, Joshua E; El-Deiry, Wafik S

    2014-12-30

    We previously identified TRAIL-inducing compound 10 (TIC10), also known as NSC350625 or ONC201, from a NCI chemical library screen as a small molecule that has potent anti-tumor efficacy and a benign safety profile in preclinical cancer models. The chemical structure that was originally published by Stahle, et. al. in the patent literature was described as an imidazo[1,2-a]pyrido[4,3-d]pyrimidine derivative. The NCI and others generally accepted this as the correct structure, which was consistent with the mass spectrometry analysis outlined in the publication by Allen et. al. that first reported the molecule's anticancer properties. A recent publication demonstrated that the chemical structure of ONC201 material from the NCI is an angular [3,4-e] isomer of the originally disclosed, linear [4,3-d] structure. Here we confirm by NMR and X-ray structural analysis of the dihydrochloride salt form that the ONC201 material produced by Oncoceutics is the angular [3,4-e] structure and not the linear structure originally depicted in the patent literature and by the NCI. Similarly, in accordance with our biological evaluation, the previously disclosed anti-cancer activity is associated with the angular structure and not the linear isomer. Together these studies confirm that ONC201, produced by Oncoceutics or obtained from the NCI, possesses an angular [3,4-e] structure that represents the highly active anti-cancer compound utilized in prior preclinical studies and now entering clinical trials in advanced cancers.

  4. Daily rhythmicity of body temperature in the dog.

    Science.gov (United States)

    Refinetti, R; Piccione, G

    2003-08-01

    Research over the past 50 years has demonstrated the existence of circadian or daily rhythmicity in the body core temperature of a large number of mammalian species. However, previous studies have failed to identify daily rhythmicity of body temperature in dogs. We report here the successful recording of daily rhythms of rectal temperature in female Beagle dogs. The low robustness of the rhythms (41% of maximal robustness) and the small range of excursion (0.5 degrees C) are probably responsible for previous failures in detecting rhythmicity in dogs.

  5. Impact of gastroesophageal reflux disease on work absenteeism, presenteeism and productivity in daily life: a European observational study

    Science.gov (United States)

    Gisbert, Javier P; Cooper, Alun; Karagiannis, Dimitrios; Hatlebakk, Jan; Agréus, Lars; Jablonowski, Helmut; Nuevo, Javier

    2009-01-01

    Background The RANGE (Retrospective ANalysis of GastroEsophageal reflux disease [GERD]) study assessed differences among patients consulting a primary care physician due to GERD-related reasons in terms of: symptoms, diagnosis and management, response to treatment, and effects on productivity, costs and health-related quality of life. This subanalysis of RANGE determined the impact of GERD on productivity in work and daily life. Methods RANGE was conducted at 134 primary care sites across six European countries (Germany, Greece, Norway, Spain, Sweden and the UK). All subjects (aged ≥18 years) who consulted with their primary care physician over a 4-month identification period were screened retrospectively, and those consulting at least once for GERD-related reasons were identified (index visit). From this population, a random sample was selected to enter the study and attended a follow-up appointment, during which the impact of GERD on productivity while working (absenteeism and presenteeism) and in daily life was evaluated using the self-reported Work Productivity and Activity Impairment Questionnaire for patients with GERD (WPAI-GERD). Results Overall, 373,610 subjects consulted with their primary care physician over the 4-month identification period, 12,815 for GERD-related reasons (3.4%); 2678 randomly selected patients attended the follow-up appointment. Average absenteeism due to GERD was highest in Germany (3.2 hours/week) and lowest in the UK (0.4 hours/week), with an average of up to 6.7 additional hours/week lost due to presenteeism in Norway. The average monetary impact of GERD-related work absenteeism and presenteeism were substantial in all countries (from €55/week per employed patient in the UK to €273/patient in Sweden). Reductions in productivity in daily life of up to 26% were observed across the European countries. Conclusion GERD places a significant burden on primary care patients, in terms of work absenteeism and presenteeism and in daily

  6. Impact of gastroesophageal reflux disease on work absenteeism, presenteeism and productivity in daily life: a European observational study

    Directory of Open Access Journals (Sweden)

    Hatlebakk Jan

    2009-10-01

    Full Text Available Abstract Background The RANGE (Retrospective ANalysis of GastroEsophageal reflux disease [GERD] study assessed differences among patients consulting a primary care physician due to GERD-related reasons in terms of: symptoms, diagnosis and management, response to treatment, and effects on productivity, costs and health-related quality of life. This subanalysis of RANGE determined the impact of GERD on productivity in work and daily life. Methods RANGE was conducted at 134 primary care sites across six European countries (Germany, Greece, Norway, Spain, Sweden and the UK. All subjects (aged ≥18 years who consulted with their primary care physician over a 4-month identification period were screened retrospectively, and those consulting at least once for GERD-related reasons were identified (index visit. From this population, a random sample was selected to enter the study and attended a follow-up appointment, during which the impact of GERD on productivity while working (absenteeism and presenteeism and in daily life was evaluated using the self-reported Work Productivity and Activity Impairment Questionnaire for patients with GERD (WPAI-GERD. Results Overall, 373,610 subjects consulted with their primary care physician over the 4-month identification period, 12,815 for GERD-related reasons (3.4%; 2678 randomly selected patients attended the follow-up appointment. Average absenteeism due to GERD was highest in Germany (3.2 hours/week and lowest in the UK (0.4 hours/week, with an average of up to 6.7 additional hours/week lost due to presenteeism in Norway. The average monetary impact of GERD-related work absenteeism and presenteeism were substantial in all countries (from €55/week per employed patient in the UK to €273/patient in Sweden. Reductions in productivity in daily life of up to 26% were observed across the European countries. Conclusion GERD places a significant burden on primary care patients, in terms of work absenteeism and

  7. Probability Distribution and Projected Trends of Daily Precipitation in China

    Institute of Scientific and Technical Information of China (English)

    CAO; Li-Ge; ZHONG; Jun; SU; Bu-Da; ZHAI; Jian-Qing; Macro; GEMMER

    2013-01-01

    Based on observed daily precipitation data of 540 stations and 3,839 gridded data from the high-resolution regional climate model COSMO-Climate Limited-area Modeling(CCLM)for 1961–2000,the simulation ability of CCLM on daily precipitation in China is examined,and the variation of daily precipitation distribution pattern is revealed.By applying the probability distribution and extreme value theory to the projected daily precipitation(2011–2050)under SRES A1B scenario with CCLM,trends of daily precipitation series and daily precipitation extremes are analyzed.Results show that except for the western Qinghai-Tibetan Plateau and South China,distribution patterns of the kurtosis and skewness calculated from the simulated and observed series are consistent with each other;their spatial correlation coefcients are above 0.75.The CCLM can well capture the distribution characteristics of daily precipitation over China.It is projected that in some parts of the Jianghuai region,central-eastern Northeast China and Inner Mongolia,the kurtosis and skewness will increase significantly,and precipitation extremes will increase during 2011–2050.The projected increase of maximum daily rainfall and longest non-precipitation period during flood season in the aforementioned regions,also show increasing trends of droughts and floods in the next 40 years.

  8. Data base for a CANDU-PHW operating on a once-through natural uranium cycle

    International Nuclear Information System (INIS)

    1979-07-01

    This report, prepared for INFCE, describes a standard 600 MW(e) CANDU-PHW reactor operating on a once-through natural uranium fuel cycle. Subsequently, data are given for an extrapolated 1000 MW(e) design (the nominal capacity adopted for the INFCE study) operating on the same fuel cycle. (author)

  9. Generalized additive model of air pollution to daily mortality

    International Nuclear Information System (INIS)

    Kim, J.; Yang, H.E.

    2005-01-01

    The association of air pollution with daily mortality due to cardiovascular disease, respiratory disease, and old age (65 or older) in Seoul, Korea was investigated in 1999 using daily values of TSP, PM10, O 3 , SO 2 , NO 2 , and CO. Generalized additive Poisson models were applied to allow for the highly flexible fitting of daily trends in air pollution as well as nonlinear association with meteorological variables such as temperature, humidity, and wind speed. To estimate the effect of air pollution and weather on mortality, LOESS smoothing was used in generalized additive models. The findings suggest that air pollution levels affect significantly the daily mortality. (orig.)

  10. Development of once-through type densitometer

    International Nuclear Information System (INIS)

    Onozawa, Atsushi; Kushida, Teruo; Kanazawa, Hiroyuki

    2004-11-01

    The swelling (volume change) observed on irradiated fuels is caused by the accumulation of fission products (FP) and irradiation defects. The swelling ratio could be changed along with radius region in the pellet due to burn up difference and irradiation temperature. Hence the density of the pellet is different between the center and outer regions of the pellet cross section. To investigate the swelling behavior at the small area of the pellet, it is needed to measure the density of fuel fragments picked from an irradiated pellet. However, the conventional densitometer for irradiated specimens in Reactor Fuel Examination Facility is designed for measuring the whole fuel pellet and is not available for precise density measurement of the small size specimen. In this circumstance, once-through type densitometer was developed to measure the density of the small irradiated specimen precisely and to handle the samples easily with remote control systems. Aimed accuracy is within 1.0%TD and precision is within 1.0% on a φ3 x 1t mm specimen. Several kinds of metallic and ceramic standard specimens are prepared to investigate the dependence of the sample weight, density and porosity on the accuracy. The results of characteristic examination using these specimens indicate that this densitometer has enough accuracy. In addition, some parts of this apparatus are controlled by motor drive units, which made it possible to measure the density full-automatically. In near future, this apparatus will be installed in a hot cell to investigate the swelling behavior at the small area of irradiated fuels and materials. (author)

  11. Global freshwater thermal emissions from steam-electric power plants with once-through cooling systems

    International Nuclear Information System (INIS)

    Raptis, Catherine E.; Pfister, Stephan

    2016-01-01

    Large quantities of heat are rejected into freshwater bodies from power plants employing once-through cooling systems, often leading to temperature increases that disturb aquatic ecosystems. The objective of this work was to produce a high resolution global picture of power-related freshwater thermal emissions and to analyse the technological, geographical and chronological patterns behind them. The Rankine cycle was systematically solved for ∼2400 generating units with once-through cooling systems, distinguishing between simple and cogenerative cycles, giving the rejected heat as a direct output. With large unit sizes, low efficiencies, and high capacity factors, nuclear power plants reject 3.7 GW heat into freshwater on average, contrasting with 480 MW rejected from coal and gas power plants. Together, nuclear and coal-fuelled power plants from the 1970s and 1980s account for almost 50% of the rejected heat worldwide, offering motivation for their phasing out in the future. Globally, 56% of the emissions are rejected into rivers, pointing to potential areas of high thermal pollution, with the rest entering lakes and reservoirs. The outcome of this work can be used to further investigate the identified thermal emission hotspots, and to calculate regionalized water temperature increase and related impacts in environmental, energy-water nexus studies and beyond. - Highlights: • The thermodynamic cycles of ∼2400 power units with once-through cooling were solved. • Global freshwater heat emissions depend on technology, geography & chronology. • Half the global emissions come from nuclear and coal plants from the 70s & 80s. • Hotspots of freshwater thermal emissions were identified globally. • Global georeferenced emissions are available for use in water temperature models.

  12. Research on Group Operation Mode of Once-through Steam Generator

    International Nuclear Information System (INIS)

    Hao, Cheng Ming; Liu, Xinkai; Peng, Min Jun; Xia, Genglei

    2011-01-01

    Integrated Pressurized Water Reactor (IPWR) owns more than one once-through steam generators (OTSGs). Flow instability may occur in secondary side of OTSG under certain conditions. Trying to avoid the occurrence of flow instability is of great important for the safe and stable operation of OTSG. Because of the fact that flow instability often occurs in certain regions, so when OTSGs operate with low load, OTSGs can be separated into several groups, which can avoid flow instability. In this paper, operational characteristics of IPWR are analyzed by RELAP5/MOD3.4 code and during the discussion of group operation, a rapid change load operation scheme using OTSG group operation mode which can be used in IPWR is proposed

  13. Research on Group Operation Mode of Once-through Steam Generator

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Cheng Ming; Liu, Xinkai; Peng, Min Jun; Xia, Genglei [Harbin Engineering University, Harbin (China)

    2011-08-15

    Integrated Pressurized Water Reactor (IPWR) owns more than one once-through steam generators (OTSGs). Flow instability may occur in secondary side of OTSG under certain conditions. Trying to avoid the occurrence of flow instability is of great important for the safe and stable operation of OTSG. Because of the fact that flow instability often occurs in certain regions, so when OTSGs operate with low load, OTSGs can be separated into several groups, which can avoid flow instability. In this paper, operational characteristics of IPWR are analyzed by RELAP5/MOD3.4 code and during the discussion of group operation, a rapid change load operation scheme using OTSG group operation mode which can be used in IPWR is proposed.

  14. Observability of market daily volatility

    Science.gov (United States)

    Petroni, Filippo; Serva, Maurizio

    2016-02-01

    We study the price dynamics of 65 stocks from the Dow Jones Composite Average from 1973 to 2014. We show that it is possible to define a Daily Market Volatility σ(t) which is directly observable from data. This quantity is usually indirectly defined by r(t) = σ(t) ω(t) where the r(t) are the daily returns of the market index and the ω(t) are i.i.d. random variables with vanishing average and unitary variance. The relation r(t) = σ(t) ω(t) alone is unable to give an operative definition of the index volatility, which remains unobservable. On the contrary, we show that using the whole information available in the market, the index volatility can be operatively defined and detected.

  15. New daily-persistent headache versus tension-type headache.

    Science.gov (United States)

    Robbins, Matthew S; Crystal, Sara C

    2010-12-01

    New daily-persistent headache (NDPH) and chronic tension-type headache (CTTH) are two forms of primary chronic daily headache of long duration that often are similar in their headache manifestations. NDPH distinguishes itself from CTTH and the other forms of chronic daily headache by its continuous head pain from onset. However, despite formalized criteria that specify NDPH must resemble the acute onset of a headache identical to that of CTTH, NDPH commonly has migraine features. Here, we review the available literature on NDPH and compare its clinical features, epidemiology, prognosis, inciting factors, and treatment to CTTH.

  16. Optimum thermal sizing and operating conditions for once through steam generator

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Kunwoo; Ju, Kyongin; Im, Inyoung; Kim, Eunkee [KEPCO Engineering and Construction Company., Inc., Daejeon (Korea, Republic of)

    2014-10-15

    The steam generator is designed to be optimized so as to remove heat and to produce steam vapor. Because of its importance, theoretical and experimental researches have been performed on forced convection boiling heat transfer. The purpose of this study is to predict the thermal behavior and to perform optimum thermal sizing of once through steam generator. To estimate the tube thermal sizing and operating conditions of the steam generator, the analytical modeling is employed on the basis of the empirical correlation equations and theory. The optimized algorithm model, Non-dominated Sorting Genetic Algorithm (NSGA)-II, uses for this analysis. This research is focused on the design of in-vessel steam generator. An one dimensional analysis code is developed to evaluate previous researches and to optimize steam generator design parameters. The results of one-dimensional analysis need to be verified with experimental data. Goals of multi-objective optimization are to minimize tube length, pressure drop and tube number. Feedwater flow rate up to 115.425kg/s is selected so as to have margin of feedwater temperature 20 ..deg. C. For the design of 200MWth once through steam generator, it is evaluated that the tube length shall be over 12.0m for the number of tubes, 2500ea, and the length of the tube shall be over 8.0m for the number of tubes, 4500ea. The parallel coordinates chart can be provided to determine the optimal combination of number of tube, pressure drop, tube diameter and length.

  17. Daily House Price Indices: Construction, Modeling, and Longer-Run Predictions

    DEFF Research Database (Denmark)

    Bollerslev, Tim; Patton, Andrew J.; Wang, Wenjing

    We construct daily house price indices for ten major U.S. metropolitan areas. Our calculations are based on a comprehensive database of several million residential property transactions and a standard repeat-sales method that closely mimics the methodology of the popular monthly Case-Shiller house...... price indices. Our new daily house price indices exhibit dynamic features similar to those of other daily asset prices, with mild autocorrelation and strong conditional heteroskedasticity of the corresponding daily returns. A relatively simple multivariate time series model for the daily house price...... index returns, explicitly allowing for commonalities across cities and GARCH effects, produces forecasts of monthly house price changes that are superior to various alternative forecast procedures based on lower frequency data....

  18. Diagnosis of three types of constant faults in read-once contact networks over finite bases

    KAUST Repository

    Busbait, Monther I.; Moshkov, Mikhail

    2016-01-01

    We study the depth of decision trees for diagnosis of three types of constant faults in read-once contact networks over finite bases containing only indecomposable networks. For each basis and each type of faults, we obtain a linear upper bound

  19. Thermal-Hydraulic Analysis of a Once-Through Steam Generator Considering Performance Degradation

    International Nuclear Information System (INIS)

    Han, Hun Sik; Kang, Han Ok; Yoon, Ju Hyeon; Kim, Young In; Song, Jae Seung; Kim, Keung Koo

    2016-01-01

    Several countries have entered into a global race for the commercialization of SMRs, and considerable research and development have been implemented. Among the various reactor designs, many SMRs have adopted an integral type pressurized water reactor (PWR) to enhance the nuclear safety and system reliability. In the integral reactor design, a single reactor pressure vessel contains primary system components such as fuel and core, steam generators, pumps, and a pressurizer. For the component integration into a reactor vessel, it is important to design each component as small as possible. Thus, it is a common practice to employ a once-through steam generator in the integral reactor design due to its advantages in compactness. In general, gradual degradation in thermal-hydraulic performance of the steam generator occurs with time, and it changes slowly the operating point of the steam generator during plant lifetime. Numerical solutions are acquired to evaluate the thermal-hydraulic performance of the steam generator at various AUFs. The design results obtained show that the average tube length of the steam generator is augmented with the increase of design margin to compensate for the design uncertainties and heat transfer area reduction by plugging, fouling, etc. A helically coiled tube once-through steam generator with 30% design margin is considered for comparison of thermal-hydraulic performances according to the degradation rate

  20. Thermal-Hydraulic Analysis of a Once-Through Steam Generator Considering Performance Degradation

    Energy Technology Data Exchange (ETDEWEB)

    Han, Hun Sik; Kang, Han Ok; Yoon, Ju Hyeon; Kim, Young In; Song, Jae Seung; Kim, Keung Koo [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    Several countries have entered into a global race for the commercialization of SMRs, and considerable research and development have been implemented. Among the various reactor designs, many SMRs have adopted an integral type pressurized water reactor (PWR) to enhance the nuclear safety and system reliability. In the integral reactor design, a single reactor pressure vessel contains primary system components such as fuel and core, steam generators, pumps, and a pressurizer. For the component integration into a reactor vessel, it is important to design each component as small as possible. Thus, it is a common practice to employ a once-through steam generator in the integral reactor design due to its advantages in compactness. In general, gradual degradation in thermal-hydraulic performance of the steam generator occurs with time, and it changes slowly the operating point of the steam generator during plant lifetime. Numerical solutions are acquired to evaluate the thermal-hydraulic performance of the steam generator at various AUFs. The design results obtained show that the average tube length of the steam generator is augmented with the increase of design margin to compensate for the design uncertainties and heat transfer area reduction by plugging, fouling, etc. A helically coiled tube once-through steam generator with 30% design margin is considered for comparison of thermal-hydraulic performances according to the degradation rate.

  1. Lightship Daily Observations - NARA Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Observations taken on board lightships along the United States coasts from 1893 - 1943. Generally 4-6 observations daily. Also includes deck logs, which give...

  2. Impact of intestinal stoma of daily activities

    OpenAIRE

    Kougl, Jiří

    2016-01-01

    In the theoretical part I am devoted to the history, anatomy, types of stoma, concept of stoma, indications for an establishment of stoma, pre and postoperative care, treatment of stoma, instruments and the influence on daily activities of a client while having a stoma. In the practical part I am following my own research of the impact of stoma on daily life's activities of klients with a stoma.

  3. Daily negative affect and smoking after a self-set quit attempt: The role of dyadic invisible social support in a daily diary study.

    Science.gov (United States)

    Lüscher, Janina; Stadler, Gertraud; Ochsner, Sibylle; Rackow, Pamela; Knoll, Nina; Hornung, Rainer; Scholz, Urte

    2015-11-01

    Social support receipt from one's partner is assumed to be beneficial for successful smoking cessation. However, support receipt can have costs. Recent research suggests that the most effective support is unnoticed by the receiver (i.e., invisible). Therefore, this study examined the association between everyday levels of dyadic invisible emotional and instrumental support, daily negative affect, and daily smoking after a self-set quit attempt in smoker-non-smoker couples. Overall, 100 smokers (72.0% men, mean age M = 40.48, SD = 9.82) and their non-smoking partners completed electronic diaries from a self-set quit date on for 22 consecutive days, reporting daily invisible emotional and instrumental social support, daily negative affect, and daily smoking. Same-day multilevel analyses showed that at the between-person level, higher individual mean levels of invisible emotional and instrumental support were associated with less daily negative affect. In contrast to our assumption, more receipt of invisible emotional and instrumental support was related to more daily cigarettes smoked. The findings are in line with previous results, indicating invisible support to have beneficial relations with affect. However, results emphasize the need for further prospective daily diary approaches for understanding the dynamics of invisible support on smoking cessation. Statement of contribution What is already known on this subject? Social support receipt from a close other has proven to have emotional costs. According to current studies, the most effective social support is unnoticed by the receiver (i.e., invisible). There is empirical evidence for beneficial effects of invisible social support on affective well-being. What does this study add? Confirming benefits of invisible social support for negative affect in a health behaviour change setting Providing first evidence for detrimental effects of invisible social support on smoking. © 2015 The British Psychological Society.

  4. MO-G-BRE-04: Automatic Verification of Daily Treatment Deliveries and Generation of Daily Treatment Reports for a MR Image-Guided Treatment Machine

    International Nuclear Information System (INIS)

    Yang, D; Li, X; Li, H; Wooten, H; Green, O; Rodriguez, V; Mutic, S

    2014-01-01

    Purpose: Two aims of this work were to develop a method to automatically verify treatment delivery accuracy immediately after patient treatment and to develop a comprehensive daily treatment report to provide all required information for daily MR-IGRT review. Methods: After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a novel MR-IGRT treatment machine, we designed a method to use 1) treatment plan files, 2) delivery log files, and 3) dosimetric calibration information to verify the accuracy and completeness of daily treatment deliveries. The method verifies the correctness of delivered treatment plans and beams, beam segments, and for each segment, the beam-on time and MLC leaf positions. Composite primary fluence maps are calculated from the MLC leaf positions and the beam-on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. We also designed the daily treatment delivery report by including all required information for MR-IGRT and physics weekly review - the plan and treatment fraction information, dose verification information, daily patient setup screen captures, and the treatment delivery verification results. Results: The parameters in the log files (e.g. MLC positions) were independently verified and deemed accurate and trustable. A computer program was developed to implement the automatic delivery verification and daily report generation. The program was tested and clinically commissioned with sufficient IMRT and 3D treatment delivery data. The final version has been integrated into a commercial MR-IGRT treatment delivery system. Conclusion: A method was developed to automatically verify MR-IGRT treatment deliveries and generate daily treatment reports. Already in clinical use since December 2013, the system is able to facilitate delivery error detection, and expedite physician daily IGRT review and physicist weekly chart

  5. Instantaneous-to-daily GPP upscaling schemes based on a coupled photosynthesis-stomatal conductance model: correcting the overestimation of GPP by directly using daily average meteorological inputs.

    Science.gov (United States)

    Wang, Fumin; Gonsamo, Alemu; Chen, Jing M; Black, T Andrew; Zhou, Bin

    2014-11-01

    Daily canopy photosynthesis is usually temporally upscaled from instantaneous (i.e., seconds) photosynthesis rate. The nonlinear response of photosynthesis to meteorological variables makes the temporal scaling a significant challenge. In this study, two temporal upscaling schemes of daily photosynthesis, the integrated daily model (IDM) and the segmented daily model (SDM), are presented by considering the diurnal variations of meteorological variables based on a coupled photosynthesis-stomatal conductance model. The two models, as well as a simple average daily model (SADM) with daily average meteorological inputs, were validated using the tower-derived gross primary production (GPP) to assess their abilities in simulating daily photosynthesis. The results showed IDM closely followed the seasonal trend of the tower-derived GPP with an average RMSE of 1.63 g C m(-2) day(-1), and an average Nash-Sutcliffe model efficiency coefficient (E) of 0.87. SDM performed similarly to IDM in GPP simulation but decreased the computation time by >66%. SADM overestimated daily GPP by about 15% during the growing season compared to IDM. Both IDM and SDM greatly decreased the overestimation by SADM, and improved the simulation of daily GPP by reducing the RMSE by 34 and 30%, respectively. The results indicated that IDM and SDM are useful temporal upscaling approaches, and both are superior to SADM in daily GPP simulation because they take into account the diurnally varying responses of photosynthesis to meteorological variables. SDM is computationally more efficient, and therefore more suitable for long-term and large-scale GPP simulations.

  6. Diagnosis of constant faults in read-once contact networks over finite bases

    KAUST Repository

    Busbait, Monther I.; Chikalov, Igor; Hussain, Shahid; Moshkov, Mikhail

    2015-01-01

    We study the depth of decision trees for diagnosis of constant 0 and 1 faults in read-once contact networks over finite bases containing only indecomposable networks. For each basis, we obtain a linear upper bound on the minimum depth of decision trees depending on the number of edges in the networks. For bases containing networks with at most 10 edges we find coefficients for linear bounds which are close to sharp. © 2014 Elsevier B.V. All rights reserved.

  7. Diagnosis of constant faults in read-once contact networks over finite bases

    KAUST Repository

    Busbait, Monther I.

    2015-03-01

    We study the depth of decision trees for diagnosis of constant 0 and 1 faults in read-once contact networks over finite bases containing only indecomposable networks. For each basis, we obtain a linear upper bound on the minimum depth of decision trees depending on the number of edges in the networks. For bases containing networks with at most 10 edges we find coefficients for linear bounds which are close to sharp. © 2014 Elsevier B.V. All rights reserved.

  8. Effects of daily food processing on allergenicity.

    Science.gov (United States)

    Cabanillas, Beatriz; Novak, Natalija

    2017-08-11

    Daily food processing has the potential to alter the allergenicity of foods due to modification of the physico-chemical properties of proteins. The degree of such modifications depends on factors such as processing conditions, type of food considered, allergenic content, etc. The impact of daily food processing like boiling, roasting, frying or baking on food allergenicity have been extensively studied. The influence of other thermal treatments such as microwave heating or pressure cooking on allergenicity has also been analyzed. Non-thermal treatment such as peeling impacts on the allergenic content of certain foods such as fruits. In this review, we give an updated overview of the effects of daily processing treatments on the allergenicity of a wide variety of foods. The different variables that contribute to the modification of food allergenicity due to processing are also reviewed and discussed.

  9. Diferencias individuales y burnout en médicos oncólogos venezolanos / Individual Differences and Burnout in Venezuelan Oncologists

    Directory of Open Access Journals (Sweden)

    Blanca Torres

    2013-03-01

    Full Text Available El presente estudio explora la influencia de ciertas diferencias individuales como la sensibilidad emocional, los estilos de afrontamiento y los estilos de comunicación sobre el burnout de médicos oncólogos venezolanos. Participaron en el estudio 93 médicos oncólogos de diversos hospitales oncológicos públicos de Caracas (Venezuela, quienes completaron los cuestionarios que evaluaban las variables mencionadas. Los resultados indicaron niveles medios de burnout en los médicos estudiados, una mayor sensibilidad emocional positiva, adopción de funcionales estilos de afrontamiento y estilos de comunicación más centrados en sí mismos. Por su parte, el análisis de regresión reveló que una mayor sensibilidad egocéntrica negativa y una menor sensibilidad interpersonal positiva determinan mayores niveles de burnout en los oncólogos.

  10. Does altered fractionation influence the risk of radiation-induced optic neuropathy?

    International Nuclear Information System (INIS)

    Bhandare, Niranjan; Monroe, Alan T.; Morris, Christopher G.; Bhatti, M. Tariq; Mendenhall, William M.

    2005-01-01

    Purpose: To analyze the parameters that influence the risk of radiation-induced optic neuropathy (RION) after radiotherapy for head-and-neck tumors. Methods and Materials: Between 1964 and 2000, 273 patients with tumors of the nasopharynx, paranasal sinuses, nasal cavity, and hard palate adenoid cystic carcinomas were treated with curative intent and had radiation fields that included the optic nerves and/or chiasm. Patients were followed for at least 1 year after radiotherapy. Results: Radiation-induced optic neuropathy developed in 32 eyes of 24 patients (9%). The 5-year rates of freedom from RION according to the total dose and once- vs. twice-daily fractionation were as follows: ≤63 Gy once daily, 95%; ≤63 Gy twice daily, 98%; >63 Gy once daily, 78%; and >63 Gy twice daily, 91%. Multivariate analysis revealed that the total dose affected the risk of RION (p = 0.0047), with patient age (p = 0.0909), once-daily vs. twice-daily fractionation (p = 0.0684), and overall treatment time (p = 0.0972) were marginally significant. The use of adjuvant chemotherapy did not significantly influence the likelihood of developing RION. Conclusion: The likelihood of developing RION is primarily influenced by the total dose. Hyperfractionation may reduce the risk of experiencing this complication

  11. A dynamic model used for controller design of a coal fired once-through boiler-turbine unit

    International Nuclear Information System (INIS)

    Liu, Ji-Zhen; Yan, Shu; Zeng, De-Liang; Hu, Yong; Lv, You

    2015-01-01

    Supercritical OTB (once-through boiler) units with high steam temperature and pressure have been widely used in modern power plants due to their high cycle efficiency and less emissions. To ensure the effective operation of such power generation systems, it is necessary to build a model for the design of the overall control system. There are already detailed models of once-through boilers; however, their complexity prevents them from being applied in the controller design. This study describes a lumped parameter dynamic model that has a relatively low complexity while faithfully capturing the essential overall plant dynamics. The model structure was derived by fundamental physical laws utilizing reasonable simplifications and data analysis to avoid the phase transition position problem. Parameter identification for the model structure was completed using operational data from a 1000 MW ultra-supercritical OTB. The model was determined to be reasonable by comparison tests between computed data and measured data for both steady and dynamic states. The simplified model is verified to have appropriate fidelity in control system design to achieve effective and economic operation of the unit. - Highlights: • A simplified dynamic model of once-through boiler-turbine unit is given. • The essential dynamics of active power and throttle pressure is presented. • The change of phase transition position is avoided in modeling process. • The model has appropriate complexity and fidelity for controller design.

  12. Presentation of chronic daily headache : A clinical study

    NARCIS (Netherlands)

    Spierings, E L H; Schroevers, M.; Honkoop, P.C.; Sorbi, M.

    We studied the presentation of chronic daily headache in 258 patients from a private headache practice, 50 men and 208 women. Chronic daily headache was defined as headaches, occurring at least 5 days per week for at least 1 year. Seventy-seven percent of the patients experienced the onset of

  13. Alcohol Mixed with Energy Drinks: Daily Context of Use.

    Science.gov (United States)

    Linden-Carmichael, Ashley N; Lau-Barraco, Cathy

    2017-04-01

    The link between use of alcohol mixed with energy drinks (AmEDs) and alcohol-related harms is well established, but limited research has examined the context in which AmEDs are consumed. Identifying the social and environmental characteristics of use may illuminate whether AmEDs are used in settings that could increase the likelihood of engaging in risky behaviors or experiencing harms. This study used a 2-week daily diary assessment to compare days in which AmEDs were consumed ("AmED days") and days where other types of alcohol were used ("non-AmED days") on where, when, and with whom drinking occurred. Participants were 122 (90 women) heavy drinking college students who reported mixing caffeine with alcohol at least once in the past week. Data were collected across 389 drinking days; 40 of these days involved AmED use. Multilevel modeling findings revealed that odds of drinking AmEDs were higher on days where individuals drank at a bar or club and drank at home relative to other locations. In addition, odds of pregaming were higher on AmED days as compared to non-AmED days. AmED use was linked with lower odds of drinking game behavior. Overall, AmEDs appear to be consumed in potentially risky contexts. In combination with prior findings that AmED days are linked with heavier alcohol use and more harms experienced, these findings support the unique nature of AmED consumption in terms of the factors that may predict or maintain potentially hazardous drinking patterns. Copyright © 2017 by the Research Society on Alcoholism.

  14. Functional tasks exercise improves daily function in older women

    OpenAIRE

    Vreede, P.L. de

    2006-01-01

    Ageing is characterised by a reduction in physical reserve, the physiological capacity in excess of that needed for daily activities, that provides a margin of safety that absorbs age- or disease-related changes without a loss in function. When physical capacity falls below the ability required for the performance of daily tasks, functional limitations and a loss of independence may occur. Approximately 20% of people between 65 and 75 years of age report problems with activities of daily livi...

  15. Seasonal variation of daily physical activity in individuals with heart failure

    Directory of Open Access Journals (Sweden)

    Michael J. Shoemaker

    2016-09-01

    Full Text Available BackgroundPrevious studies indicate that seasonal variation affects daily physical activity (PA, but none have investigated this relationship in individuals with heart failure (HF who also have implanted cardioverter defibrillators and cardiac resynchronization therapy (ICD/CRT devices. The purpose of the present study was to determine if seasonal variation in temperature affects daily PA in patients with HF and ICD/CRTs.Patients and methodsSecondary analysis of data from 16 subjects with HF and Medtronic® ICD/CRT devices enrolled in a randomized trial investigating interventions to improve daily PA. Due to the rolling study enrollment, daily PA data for all subjects were not available for the entire time frame and were divided into two groups. Determination of seasonal variation of daily PA was determined using visual analysis of daily PA plotted with average temperature, autocorrelation, visual analysis of seasonal subseries plots and boxplot analysis, as well as Wilcoxon signed-rank tests.ResultsSubjects 1-8 demonstrated the greatest differences in daily PA during periods of seasonal transition whereas subjects 9-16 demonstrated the greatest variation in daily PA with greatest seasonal temperature difference. Wilcoxon signed-rank testing of the lowest and highest months for daily PA revealed median differences of 0.30 (p = 0.050 and 0.36 hours (p = 0.036 for subjects 1-8 and 9-16, with effect sizes of 0.69 and 0.74, respectively.ConclusionsSeasonal variation in mean temperature appears to affect daily PA in individuals with HF and ICD/CRT devices by a magnitude of 0.30-0.36 hours, which may need to be accounted for in future research investigating interventions to improve daily PA.

  16. Racial Differences in Exposure and Reactivity to Daily Family Stressors

    Science.gov (United States)

    Cichy, Kelly E.; Stawski, Robert S.; Almeida, David M.

    2012-01-01

    Using data from the National Study of Daily Experiences, the authors examined racial differences in exposure and reactivity to daily stressors involving family members. Respondents included African American and European American adults age 34 to 84 (N = 1,931) who participated in 8 days of daily interviews during which they reported on daily…

  17. ACRIM III Level 2 Daily Mean Data V001

    Data.gov (United States)

    National Aeronautics and Space Administration — Active Cavity Radiometer Irradiance Monitor (ACRIM) III Level 2 Daily Mean Data product consists of Level 2 total solar irradiance in the form of daily means...

  18. Daily Medicine Record for Your Child

    Science.gov (United States)

    ... Age: ____ 2 years old___ Weight: ___ 30 pounds ___ Daily Medicine Record Child’s name: ___________________ Today’s date: _________________ Age: ____________ Weight: ________________ (pounds) Time Problem ...

  19. Diagnosis of Constant Faults in Read-Once Contact Networks over Finite Bases using Decision Trees

    KAUST Repository

    Busbait, Monther I.

    2014-01-01

    We study the depth of decision trees for diagnosis of constant faults in read-once contact networks over finite bases. This includes diagnosis of 0-1 faults, 0 faults and 1 faults. For any finite basis, we prove a linear upper bound on the minimum

  20. Forcasting Philippine daily stock exchange index | Urrutia | Journal ...

    African Journals Online (AJOL)

    The purpose of the study is to produce a model that can estimate a three-year forecast of the Philippine Daily Stock Exchange Index. Seasonal Autoregressive Integrated Moving Average (SARIMA) model is applied ona total of 4,927 daily data observations from 1995 to 2014. By then, actual and predicted values was ...

  1. Health-related aspects of objectively measured daily physical activity in children

    DEFF Research Database (Denmark)

    Dencker, Magnus; Andersen, Lars Bo

    2008-01-01

    It is well established that physical inactivity in adults is associated with increased mortality and morbidity. Whether daily physical activity level is related to risk factors for cardiovascular disease (CVD) in children has been debated. Furthermore, objective data on the habitual daily physica...... activity. This review summarizes recently published studies that have used accelerometers to measure daily physical activity in children and related activity data to known risk factors for CVD.......It is well established that physical inactivity in adults is associated with increased mortality and morbidity. Whether daily physical activity level is related to risk factors for cardiovascular disease (CVD) in children has been debated. Furthermore, objective data on the habitual daily physical...... activity in children have at large been scarce in the literature. The main reason for this is the fact that daily physical activity is very difficult to measure in children. In recent years, a new device, the accelerometer, has emerged as a frequently used instrument for the measurement of daily physical...

  2. Nowcasting daily minimum air and grass temperature

    Science.gov (United States)

    Savage, M. J.

    2016-02-01

    Site-specific and accurate prediction of daily minimum air and grass temperatures, made available online several hours before their occurrence, would be of significant benefit to several economic sectors and for planning human activities. Site-specific and reasonably accurate nowcasts of daily minimum temperature several hours before its occurrence, using measured sub-hourly temperatures hours earlier in the morning as model inputs, was investigated. Various temperature models were tested for their ability to accurately nowcast daily minimum temperatures 2 or 4 h before sunrise. Temperature datasets used for the model nowcasts included sub-hourly grass and grass-surface (infrared) temperatures from one location in South Africa and air temperature from four subtropical sites varying in altitude (USA and South Africa) and from one site in central sub-Saharan Africa. Nowcast models used employed either exponential or square root functions to describe the rate of nighttime temperature decrease but inverted so as to determine the minimum temperature. The models were also applied in near real-time using an open web-based system to display the nowcasts. Extrapolation algorithms for the site-specific nowcasts were also implemented in a datalogger in an innovative and mathematically consistent manner. Comparison of model 1 (exponential) nowcasts vs measured daily minima air temperatures yielded root mean square errors (RMSEs) <1 °C for the 2-h ahead nowcasts. Model 2 (also exponential), for which a constant model coefficient ( b = 2.2) was used, was usually slightly less accurate but still with RMSEs <1 °C. Use of model 3 (square root) yielded increased RMSEs for the 2-h ahead comparisons between nowcasted and measured daily minima air temperature, increasing to 1.4 °C for some sites. For all sites for all models, the comparisons for the 4-h ahead air temperature nowcasts generally yielded increased RMSEs, <2.1 °C. Comparisons for all model nowcasts of the daily grass

  3. Comparative long-term trend analysis of daily weather conditions with daily pollen concentrations in Brussels, Belgium

    Science.gov (United States)

    Bruffaerts, Nicolas; De Smedt, Tom; Delcloo, Andy; Simons, Koen; Hoebeke, Lucie; Verstraeten, Caroline; Van Nieuwenhuyse, An; Packeu, Ann; Hendrickx, Marijke

    2018-03-01

    A clear rise in seasonal and annual temperatures, a gradual increase of total radiation, and a relative trend of change in seasonal precipitation have been observed for the last four decades in Brussels (Belgium). These local modifications may have a direct and indirect public health impact by altering the timing and intensity of allergenic pollen seasons. In this study, we assessed the statistical correlations (Spearman's test) between pollen concentration and meteorological conditions by using long-term daily datasets of 11 pollen types (8 trees and 3 herbaceous plants) and 10 meteorological parameters observed in Brussels between 1982 and 2015. Furthermore, we analyzed the rate of change in the annual cycle of the same selected pollen types by the Mann-Kendall test. We revealed an overall trend of increase in daily airborne tree pollen (except for the European beech tree) and an overall trend of decrease in daily airborne pollen from herbaceous plants (except for Urticaceae). These results revealed an earlier onset of the flowering period for birch, oak, ash, plane, grasses, and Urticaceae. Finally, the rates of change in pollen annual cycles were shown to be associated with the rates of change in the annual cycles of several meteorological parameters such as temperature, radiation, humidity, and rainfall.

  4. Comparative long-term trend analysis of daily weather conditions with daily pollen concentrations in Brussels, Belgium.

    Science.gov (United States)

    Bruffaerts, Nicolas; De Smedt, Tom; Delcloo, Andy; Simons, Koen; Hoebeke, Lucie; Verstraeten, Caroline; Van Nieuwenhuyse, An; Packeu, Ann; Hendrickx, Marijke

    2018-03-01

    A clear rise in seasonal and annual temperatures, a gradual increase of total radiation, and a relative trend of change in seasonal precipitation have been observed for the last four decades in Brussels (Belgium). These local modifications may have a direct and indirect public health impact by altering the timing and intensity of allergenic pollen seasons. In this study, we assessed the statistical correlations (Spearman's test) between pollen concentration and meteorological conditions by using long-term daily datasets of 11 pollen types (8 trees and 3 herbaceous plants) and 10 meteorological parameters observed in Brussels between 1982 and 2015. Furthermore, we analyzed the rate of change in the annual cycle of the same selected pollen types by the Mann-Kendall test. We revealed an overall trend of increase in daily airborne tree pollen (except for the European beech tree) and an overall trend of decrease in daily airborne pollen from herbaceous plants (except for Urticaceae). These results revealed an earlier onset of the flowering period for birch, oak, ash, plane, grasses, and Urticaceae. Finally, the rates of change in pollen annual cycles were shown to be associated with the rates of change in the annual cycles of several meteorological parameters such as temperature, radiation, humidity, and rainfall.

  5. 41 CFR 301-50.7 - Should I use the online self-service booking tool once ETS is available within my agency?

    Science.gov (United States)

    2010-07-01

    ... SERVICES § 301-50.7 Should I use the online self-service booking tool once ETS is available within my agency? Yes, you should use the online self-service booking tool offered by ETS or your agency's TMS... self-service booking tool once ETS is available within my agency? 301-50.7 Section 301-50.7 Public...

  6. Understanding metropolitan patterns of daily encounters.

    Science.gov (United States)

    Sun, Lijun; Axhausen, Kay W; Lee, Der-Horng; Huang, Xianfeng

    2013-08-20

    Understanding of the mechanisms driving our daily face-to-face encounters is still limited; the field lacks large-scale datasets describing both individual behaviors and their collective interactions. However, here, with the help of travel smart card data, we uncover such encounter mechanisms and structures by constructing a time-resolved in-vehicle social encounter network on public buses in a city (about 5 million residents). Using a population scale dataset, we find physical encounters display reproducible temporal patterns, indicating that repeated encounters are regular and identical. On an individual scale, we find that collective regularities dominate distinct encounters' bounded nature. An individual's encounter capability is rooted in his/her daily behavioral regularity, explaining the emergence of "familiar strangers" in daily life. Strikingly, we find individuals with repeated encounters are not grouped into small communities, but become strongly connected over time, resulting in a large, but imperceptible, small-world contact network or "structure of co-presence" across the whole metropolitan area. Revealing the encounter pattern and identifying this large-scale contact network are crucial to understanding the dynamics in patterns of social acquaintances, collective human behaviors, and--particularly--disclosing the impact of human behavior on various diffusion/spreading processes.

  7. Management of small-for-gestational-age twins with absent/reversed end diastolic flow in the umbilical artery: outcome of a policy of daily biophysical profile (BPP).

    Science.gov (United States)

    Kennelly, Máiréad M; Sturgiss, Stephen N

    2007-01-01

    To evaluate a strategy of daily biophysical profile (BPP) for pregnancies with small-for-gestational-age twins and with absent or reversed end diastolic flow (AREDF) in the umbilical artery of one twin and to assess the latency interval between detection and delivery in monochorionic (MC) and dichorionic (DC) twin pregnancy. A search of the Fetal Medicine Database was carried out between 2000 and 2005 at a single tertiary centre to identify all cases with AREDF in the umbilical artery with one small-for-gestational-age twin. Active monitoring with daily BPP was undertaken, once the estimated fetal weights (EFW) was >or= 500 g and at a gestational age of >or= 24 weeks in both twins. Delivery was timed on the basis of an abnormal BPP, two equivocal BPP within 12 h or gestational age of >or= 32(+0) weeks. Twenty-two MC and 17 DC twin pregnancies were identified. There were no fetal losses in the viable actively monitored MC (19) and DC (13) twins. There was a longer latency interval in the MC group at 21.7 days versus 14.4 days in the DC group (p = 0.13). Delivery was indicated for an abnormal BPP (57.8% MC vs 30.8% DC). A strategy of daily BPP can be used to monitor preterm twin fetuses with AREDF, prolonging pregnancy with an acceptable perinatal outcome. Copyright 2007 John Wiley & Sons, Ltd.

  8. Daily Emotional and Physical Reactivity to Stressors Among Widowed and Married Older Adults

    Science.gov (United States)

    2014-01-01

    Objectives. Widowhood may result in declines in health and potentially stressful changes to daily routines. However, little research has examined how daily stressors contribute to physical and emotional well-being in widowhood. The objectives of the current study were to examine daily stressor exposure and reactivity in widowed versus married older adults. Method. Participants included all 100 widowed and 342 married adults aged 65 and older from the National Study of Daily Experiences, a daily diary study from the second wave of the Midlife in the United States. Daily stressors were measured using the Daily Inventory of Stressful Events; multilevel modeling assessed daily reactivity to stressors using daily negative affect (emotional reactivity) and daily physical symptoms (physical reactivity) as outcomes. Results. Married participants reported more stressors in general, and specifically more interpersonal stressors (e.g., arguments). Both married and widowed participants were reactive to daily stressors. Married participants were physically and emotionally reactive to interpersonal stressors. Widowed participants were more physically reactive to home-related stressors. Discussion. Attention to the types of daily stressors that widowed older adults experience in daily life and the potential physical effects of daily stressors during widowhood may help to alleviate some of the physical distress that widowed older adults may experience. PMID:23685921

  9. Daily emotional and physical reactivity to stressors among widowed and married older adults.

    Science.gov (United States)

    Hahn, Elizabeth A; Cichy, Kelly E; Small, Brent J; Almeida, David M

    2014-01-01

    Widowhood may result in declines in health and potentially stressful changes to daily routines. However, little research has examined how daily stressors contribute to physical and emotional well-being in widowhood. The objectives of the current study were to examine daily stressor exposure and reactivity in widowed versus married older adults. Participants included all 100 widowed and 342 married adults aged 65 and older from the National Study of Daily Experiences, a daily diary study from the second wave of the Midlife in the United States. Daily stressors were measured using the Daily Inventory of Stressful Events; multilevel modeling assessed daily reactivity to stressors using daily negative affect (emotional reactivity) and daily physical symptoms (physical reactivity) as outcomes. Married participants reported more stressors in general, and specifically more interpersonal stressors (e.g., arguments). Both married and widowed participants were reactive to daily stressors. Married participants were physically and emotionally reactive to interpersonal stressors. Widowed participants were more physically reactive to home-related stressors. Attention to the types of daily stressors that widowed older adults experience in daily life and the potential physical effects of daily stressors during widowhood may help to alleviate some of the physical distress that widowed older adults may experience.

  10. Analysis of the average daily radon variations in the soil air

    International Nuclear Information System (INIS)

    Holy, K.; Matos, M.; Boehm, R.; Stanys, T.; Polaskova, A.; Hola, O.

    1998-01-01

    In this contribution the search of the relation between the daily variations of the radon concentration and the regular daily oscillations of the atmospheric pressure are presented. The deviation of the radon activity concentration in the soil air from the average daily value reaches only a few percent. For the dry summer months the average daily course of the radon activity concentration can be described by the obtained equation. The analysis of the average daily courses could give the information concerning the depth of the gas permeable soil layer. The soil parameter is determined by others method with difficulty

  11. Assessment of the once-through cooling alternative for central steam-electric generating stations

    Energy Technology Data Exchange (ETDEWEB)

    Paddock, R. A.; Ditmars, J. D.

    1978-12-01

    The efficacy of the disposal of waste heat from steam-electric power generation by means of once-through cooling systems was examined in the context of the physical aspects of water quality standards and guidelines for thermal discharges. Typical thermal standards for each of the four classes of water bodies (rivers, lakes, estuaries, and coastal waters) were identified. The mixing and dilution characteristics of various discharge modes ranging from simple, shoreline surface discharges to long, submerged multiport diffusers were examined in terms of the results of prototype measurements, analytical model predictions, and physical model studies. General guidelines were produced that indicate, for a given plant capacity, a given type of receiving water body, and a given discharge mode, the likelihood that once-through cooling can be effected within the restrictions of typical thermal standards. In general, it was found that shoreline surface discharges would not be adequate for large power plants (greater than or equal to 500 MW) at estuarine and marine coastal sites, would be marginally adequate at lake sites, and would be acceptable only at river sites with large currents and river discharges. Submerged multiport diffusers were found to provide the greatest likelihood of meeting thermal standards in all receiving water environments.

  12. Assessment of the once-through cooling alternative for central steam-electric generating stations

    International Nuclear Information System (INIS)

    Paddock, R.A.; Ditmars, J.D.

    1978-12-01

    The efficacy of the disposal of waste heat from steam-electric power generation by means of once-through cooling systems was examined in the context of the physical aspects of water quality standards and guidelines for thermal discharges. Typical thermal standards for each of the four classes of water bodies (rivers, lakes, estuaries, and coastal waters) were identified. The mixing and dilution characteristics of various discharge modes ranging from simple, shoreline surface discharges to long, submerged multiport diffusers were examined in terms of the results of prototype measurements, analytical model predictions, and physical model studies. General guidelines were produced that indicate, for a given plant capacity, a given type of receiving water body, and a given discharge mode, the likelihood that once-through cooling can be effected within the restrictions of typical thermal standards. In general, it was found that shoreline surface discharges would not be adequate for large power plants (greater than or equal to 500 MW) at estuarine and marine coastal sites, would be marginally adequate at lake sites, and would be acceptable only at river sites with large currents and river discharges. Submerged multiport diffusers were found to provide the greatest likelihood of meeting thermal standards in all receiving water environments

  13. Allegheny County Jail Daily Census

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — A daily census of the inmates at the Allegheny County Jail (ACJ). Includes gender, race, age at booking, and current age. The records for each month contain a...

  14. Study of flue-gas temperature difference in supercritical once-through boiler

    Science.gov (United States)

    Kang, Yanchang; Li, Bing; Song, Ang

    2018-02-01

    The 600 MW coal-fired once-through Boilers with opposed firing at a power plant are found to experience marked temperature variation and even overtemperature on the wall of the heating surface as a result of flue-gas temperature (FGT) variation in the boiler. In this study, operational adjustments were made to the pulverizing, combustion, and secondary air box systems in these boilers, in order to solve problems in internal combustion. The adjustments were found to reduce FGT difference and optimize the boiler’ combustion conditions. The results of this study can provide a reference for optimization of coal-fired boiler of the same type in similar conditions.

  15. Daily Autonomy Support and Sexual Identity Disclosure Predicts Daily Mental and Physical Health Outcomes.

    Science.gov (United States)

    Legate, Nicole; Ryan, Richard M; Rogge, Ronald D

    2017-06-01

    Using a daily diary methodology, we examined how social environments support or fail to support sexual identity disclosure, and associated mental and physical health outcomes. Results showed that variability in disclosure across the diary period related to greater psychological well-being and fewer physical symptoms, suggesting potential adaptive benefits to selectively disclosing. A multilevel path model indicated that perceiving autonomy support in conversations predicted more disclosure, which in turn predicted more need satisfaction, greater well-being, and fewer physical symptoms that day. Finally, mediation analyses revealed that disclosure and need satisfaction explained why perceiving autonomy support in a conversation predicted greater well-being and fewer physical symptoms. That is, perceiving autonomy support in conversations indirectly predicted greater wellness through sexual orientation disclosure, along with feeling authentic and connected in daily interactions with others. Discussion highlights the role of supportive social contexts and everyday opportunities to disclose in affecting sexual minority mental and physical health.

  16. Recall of ICU Stay in Patients Managed With a Sedation Protocol or a Sedation Protocol With Daily Interruption.

    Science.gov (United States)

    Burry, Lisa; Cook, Deborah; Herridge, Margaret; Devlin, John W; Fergusson, Dean; Meade, Maureen; Steinberg, Marilyn; Skrobik, Yoanna; Olafson, Kendiss; Burns, Karen; Dodek, Peter; Granton, John; Ferguson, Niall; Jacka, Michael; Tanios, Maged; Fowler, Robert; Reynolds, Steven; Keenan, Sean; Mallick, Ranjeeta; Mehta, Sangeeta

    2015-10-01

    To 1) describe factual, emotional, and delusional memories of ICU stay for patients enrolled in the SLEAP (Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol) trial; 2) compare characteristics of patients with and without ICU recall, and patients with and without delusional memories; and 3) determine factors associated with delusional memories 28 days after ICU discharge. Prospective cohort. Sixteen North American medical and surgical ICUs. Critically ill, mechanically ventilated adults randomized in the SLEAP trial. Post-ICU interviews on days 3, 28, and 90 using the validated ICU Memory Tool. Overall, 289 of 297 ICU survivors (97%) (146 protocolized sedation and 143 protocolized sedation plus daily interruption patients) were interviewed at least once. Because there were no differences in recall status or types of memories between the two sedation groups, we present the findings for all patients rather than by study group. On days 3, 28, and 90, 28%, 26%, and 36% of patients, respectively, reported no recall of being in the ICU (overall perception, self-reported) (p = 0.75). Mean daily doses of benzodiazepines and opioids were lower in patients with no ICU recall than those with recall (p patients reporting no recall of ICU stay on day 3, 97% and 90% reported at least one factual and one emotional memory from ICU, respectively. Emotional memories declined with time after ICU discharge, particularly panic and confusion. Delusional memories 28 days after discharge were common (70%) yet unrelated to delirium (p = 0.84), recall status (p = 0.15), total dose of benzodiazepine (p = 0.78), or opioid (p = 0.21). Delusional memories were less likely with longer duration of mechanical ventilation (odds ratio, 0.955; 95% CI, 0.91-1.00; p = 0.04). Recall of ICU stay and types of memories reported were not influenced by the trial sedation strategy. Lack of ICU recall and delusional memories were common after ICU

  17. A Simple Method Using a Topography Correction Coefficient for Estimating Daily Distribution of Solar Irradiance in Complex Terrain

    International Nuclear Information System (INIS)

    Yun, J.I.

    2009-01-01

    Accurate solar radiation data are critical to evaluate major physiological responses of plants. For most upland crops and orchard plants growing in complex terrain, however, it is not easy for farmers or agronomists to access solar irradiance data. Here we suggest a simple method using a sun-slope geometry based topographical coefficient to estimate daily solar irradiance on any sloping surfaces from global solar radiation measured at a nearby weather station. An hourly solar irradiance ratio (W i ) between sloping and horizontal surface is defined as multiplication of the relative solar intensity (k i ) and the slope irradiance ratio (r i ) at an hourly interval. The k i is the ratio of hourly solar radiation to the 24 hour cumulative radiation on a horizontal surface under clear sky conditions. The r i is the ratio of clear sky radiation on a given slope to that on a horizontal reference. Daily coefficient for slope correction is simply the sum of W i on each date. We calculated daily solar irradiance at 8 side slope locations circumventing a cone-shaped parasitic volcano (c.a., 570 m diameter for the bottom circle and 90 m bottom-to-top height) by multiplying these coefficients to the global solar radiation measured horizontally. Comparison with the measured slope irradiance from April 2007 to March 2008 resulted in the root mean square error (RMSE) of 1.61 MJ m −2 for the whole period but the RMSE for April to October (i.e., major cropping season in Korea) was much lower and satisfied the 5% error tolerance for radiation measurement. The RMSE was smallest in October regardless of slope aspect, and the aspect dependent variation of RMSE was greatest in November. Annual variation in RMSE was greatest on north and south facing slopes, followed by southwest, southeast, and northwest slopes in decreasing order. Once the coefficients are prepared, global solar radiation data from nearby stations can be easily converted to the solar irradiance map at landscape

  18. Comparative efficacy of indacaterol in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Ribeiro M

    2012-03-01

    Full Text Available Marcos Ribeiro, Kenneth R ChapmanAsthma and Airway Centre, University Health Network, Toronto Western Hospital, University of Toronto, Toronto, ON, CanadaAbstract: Long-acting bronchodilators have been shown to improve multiple clinical outcomes in chronic obstructive pulmonary disease (COPD including lung function, symptoms, dyspnea, quality of life, and exacerbations. Indacaterol is a novel, inhaled, long-acting β2-agonist providing 24-hour bronchodilation with once-daily dosing. It is currently approved for the maintenance treatment of COPD to be administered as 150 or 300 µg once-daily doses as licensed in many countries and 75 µg as licensed in the US by means of a single-dose dry powder inhaler. The data from clinical development support a favorable safety and tolerability profile within the β2-agonist drug class, with no relevant issues identified. Current evidence indicates that indacaterol is suitable for use as first-line monotherapy in COPD patients with moderate disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II and beyond that do not require an inhaled corticosteroid (ICS as per GOLD guidelines, or in combination with an ICS in severe or very severe patients with repeated exacerbations. Data from trials with the novel once-daily β2-agonist, indacaterol, indicate superior bronchodilation and clinical efficacy over twice-daily long-acting β2-agonists and at least equipotent bronchodilation as once-daily tiotropium. Bronchodilators are central in the symptomatic management of COPD. It is likely that once-daily dosing of a bronchodilator would be a significant convenience and probably a compliance-enhancing advantage, leading to improved overall clinical outcomes in patients with COPD.Keywords: indacaterol, onset of action, chronic obstructive pulmonary disease, bronchodilators, once-daily, long-acting β2-agonists

  19. Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway.

    Science.gov (United States)

    Allen, Joshua E; Krigsfeld, Gabriel; Patel, Luv; Mayes, Patrick A; Dicker, David T; Wu, Gen Sheng; El-Deiry, Wafik S

    2015-05-01

    We previously reported the identification of ONC201/TIC10, a novel small molecule inducer of the human TRAIL gene that improves efficacy-limiting properties of recombinant TRAIL and is in clinical trials in advanced cancers based on its promising safety and antitumor efficacy in several preclinical models. We performed a high throughput luciferase reporter screen using the NCI Diversity Set II to identify TRAIL-inducing compounds. Small molecule-mediated induction of TRAIL reporter activity was relatively modest and the majority of the hit compounds induced low levels of TRAIL upregulation. Among the candidate TRAIL-inducing compounds, TIC9 and ONC201/TIC10 induced sustained TRAIL upregulation and apoptosis in tumor cells in vitro and in vivo. However, ONC201/TIC10 potentiated tumor cell death while sparing normal cells, unlike TIC9, and lacked genotoxicity in normal fibroblasts. Investigating the effects of TRAIL-inducing compounds on cell signaling pathways revealed that TIC9 and ONC201/TIC10, which are the most potent inducers of cell death, exclusively activate Foxo3a through inactivation of Akt/ERK to upregulate TRAIL and its pro-apoptotic death receptor DR5. These studies reveal the selective activity of ONC201/TIC10 that led to its selection as a lead compound for this novel class of antitumor agents and suggest that ONC201/TIC10 is a unique inducer of the TRAIL pathway through its concomitant regulation of the TRAIL ligand and its death receptor DR5.

  20. ONC201 selectively induces apoptosis in cutaneous T-cell lymphoma cells via activating pro-apoptotic integrated stress response and inactivating JAK/STAT and NF-κB pathways.

    Science.gov (United States)

    Ni, Xiao; Zhang, Xiang; Hu, Cheng-Hui; Langridge, Timothy; Tarapore, Rohinton S; Allen, Joshua E; Oster, Wolfgang; Duvic, Madeleine

    2017-09-22

    Cutaneous T-cell lymphomas (CTCLs) are extremely symptomatic and still incurable, and more effective and less toxic therapies are urgently needed. ONC201, an imipridone compound, has shown efficacy in pre-clinical studies in multiple advanced cancers. This study was to evaluate the anti-tumor activity of ONC201 on CTCL cells. The effect of ONC201 on the cell growth and apoptosis were evaluated in CTCL cell lines (n=8) and primary CD4 + malignant T cells isolated from CTCL patients (n=5). ONC201 showed a time-dependent cell growth inhibition in all treated cell lines with a concentration range of 1.25-10.0 μM. ONC201 also induced apoptosis in tested cells with a narrow concentration range of 2.5-10.0 μM, evidenced by increased Annexin V + cells, accompanied by accumulated sub-G1 portions. ONC201 only induced apoptosis in CD4 + malignant T cells, not in normal CD4 + T cells. The activating transcription factor 4 (ATF4), a hallmark of integrated stress response, was upregulated in response to ONC201 whereas Akt was downregulated. In addition, molecules in JAK/STAT and NF-κB pathways, as well as IL-32β, were downregulated following ONC201 treatment. Thus, ONC201 exerts a potent and selective anti-tumor effect on CTCL cells. Its efficacy may involve activating integrated stress response through ATF4 and inactivating JAK/STAT and NF-κB pathways.