Cerebral staging of lung cancer: is one single contrast-enhanced T1-weighted three-dimensional gradient-echo sequence sufficient?

Energy Technology Data Exchange (ETDEWEB)

Ohana, Mickael; Jeung, Mi-Young; Roy, Catherine [Nouvel Hopital Civil-Hopitaux Universitaires de Strasbourg, Service de Radiologie B/Radiology Department, Strasbourg (France); Bazille, Gauthier [Clinique Saint Anne-Groupe Radiologique MIM, Strasbourg (France)

2014-08-15

Gadolinium-enhanced magnetic resonance imaging (MRI) is the gold standard for cerebral staging in thoracic oncology. We hypothesize that a minimalist examination, consisting of a single contrast-enhanced T1-weighted three-dimensional gradient-echo sequence (CE 3D-GRE), would be sufficient for the cerebral staging of nonsymptomatic lung cancer patients. Seventy nonsymptomatic patients (50 % men; 62 years ± 10.2) referred for cerebral staging of a lung cancer were retrospectively included. All underwent a standard 3 T MRI examination with T1, FLAIR, T2* GRE, diffusion, and CE 3D-GRE sequences, for a total examination time of 20 min. The sole CE 3D-GRE (acquisition time: 6 min) was extracted and blindly interpreted by two radiologists in search of brain metastases. Hemorrhagic features of potential lesions and relevant incidental findings were also noted. Discrepant cases were reviewed by a third reader. The full MRI examination and follow-up studies were used as a reference to calculate sensitivity and specificity of the sole CE 3D-GRE. Thirty-eight point six percent (27 out of 70) of the patients had brain metastases. Performances and reader's agreement with the sole CE 3D-GRE sequence were excellent for the diagnosis of brain metastases (sensitivity = 96.3 %, specificity = 100 %, κ = 0.91) and incidental findings (sensitivity = 85.7 %, specificity = 100 %, κ = 0.62) but insufficient for the identification of hemorrhages within the metastases (sensitivity = 33.3 %, specificity = 85.7 %, κ = 0.47). In the specific case of lung cancer, cerebral staging in nonsymptomatic patients can be efficiently achieved with a minimalistic protocol consisting of a single CE 3D-GRE sequence, completed if positive with a T2* sequence for hemorrhagic assessment, thus halving appointment delays. (orig.)

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.

Six steps to a successful dose-reduction strategy

International Nuclear Information System (INIS)

Bennett, M.

1995-01-01

The increased importance of demonstrating achievement of the ALARA principle has helped produce a proliferation of dose-reduction ideas. Across a company there may be many dose-reduction items being pursued in a variety of areas. However, companies have a limited amount of resource and, therefore, to ensure funding is directed to those items which will produce the most benefit and that all areas apply a common policy, requires the presence of a dose-reduction strategy. Six steps were identified in formulating the dose-reduction strategy for Rolls-Royce and Associates (RRA): (1) collating the ideas; (2) quantitatively evaluating them on a common basis; (3) prioritizing the ideas in terms of cost benefit, (4) implementation of the highest priority items; (5) monitoring their success; (6) periodically reviewing the strategy. Inherent in producing the dose-reduction strategy has been a comprehensive dose database and the RRA-developed dose management computer code DOMAIN, which allows prediction of dose rates and dose. The database enabled high task dose items to be identified, assisted in evaluating dose benefits, and monitored dose trends once items had been implemented. The DOMAIN code was used both in quantifying some of the project dose benefits and its results, such as dose contours, used in some of the dose-reduction items themselves. In all, over fifty dose-reduction items were evaluated in the strategy process and the items which will give greatest benefit are being implemented. The strategy has been successful in giving renewed impetus and direction to dose-reduction management

Six steps to a successful dose-reduction strategy

Energy Technology Data Exchange (ETDEWEB)

Bennett, M. [Rolls-Royce & Associates Ltd., Derby (United Kingdom)

1995-03-01

The increased importance of demonstrating achievement of the ALARA principle has helped produce a proliferation of dose-reduction ideas. Across a company there may be many dose-reduction items being pursued in a variety of areas. However, companies have a limited amount of resource and, therefore, to ensure funding is directed to those items which will produce the most benefit and that all areas apply a common policy, requires the presence of a dose-reduction strategy. Six steps were identified in formulating the dose-reduction strategy for Rolls-Royce and Associates (RRA): (1) collating the ideas; (2) quantitatively evaluating them on a common basis; (3) prioritizing the ideas in terms of cost benefit, (4) implementation of the highest priority items; (5) monitoring their success; (6) periodically reviewing the strategy. Inherent in producing the dose-reduction strategy has been a comprehensive dose database and the RRA-developed dose management computer code DOMAIN, which allows prediction of dose rates and dose. The database enabled high task dose items to be identified, assisted in evaluating dose benefits, and monitored dose trends once items had been implemented. The DOMAIN code was used both in quantifying some of the project dose benefits and its results, such as dose contours, used in some of the dose-reduction items themselves. In all, over fifty dose-reduction items were evaluated in the strategy process and the items which will give greatest benefit are being implemented. The strategy has been successful in giving renewed impetus and direction to dose-reduction management.

Quantitative comparison between a multiecho sequence and a single-echo sequence for susceptibility-weighted phase imaging.

Science.gov (United States)

Gilbert, Guillaume; Savard, Geneviève; Bard, Céline; Beaudoin, Gilles

2012-06-01

The aim of this study was to investigate the benefits arising from the use of a multiecho sequence for susceptibility-weighted phase imaging using a quantitative comparison with a standard single-echo acquisition. Four healthy adult volunteers were imaged on a clinical 3-T system using a protocol comprising two different three-dimensional susceptibility-weighted gradient-echo sequences: a standard single-echo sequence and a multiecho sequence. Both sequences were repeated twice in order to evaluate the local noise contribution by a subtraction of the two acquisitions. For the multiecho sequence, the phase information from each echo was independently unwrapped, and the background field contribution was removed using either homodyne filtering or the projection onto dipole fields method. The phase information from all echoes was then combined using a weighted linear regression. R2 maps were also calculated from the multiecho acquisitions. The noise standard deviation in the reconstructed phase images was evaluated for six manually segmented regions of interest (frontal white matter, posterior white matter, globus pallidus, putamen, caudate nucleus and lateral ventricle). The use of the multiecho sequence for susceptibility-weighted phase imaging led to a reduction of the noise standard deviation for all subjects and all regions of interest investigated in comparison to the reference single-echo acquisition. On average, the noise reduction ranged from 18.4% for the globus pallidus to 47.9% for the lateral ventricle. In addition, the amount of noise reduction was found to be strongly inversely correlated to the estimated R2 value (R=-0.92). In conclusion, the use of a multiecho sequence is an effective way to decrease the noise contribution in susceptibility-weighted phase images, while preserving both contrast and acquisition time. The proposed approach additionally permits the calculation of R2 maps. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of propranolol in head tremor: quantitative study following single-dose and sustained drug administration.

Science.gov (United States)

Calzetti, S; Sasso, E; Negrotti, A; Baratti, M; Fava, R

1992-12-01

The effect of the beta-adrenoceptor antagonist propranolol has been investigated in nine patients suffering from isolated (six patients) or prominent (three patients) essential tremor of the head. In a double-blind, placebo-controlled study the tremorolytic efficacy of propranolol has been assessed by a quantitative accelerometric method after a single oral dose (120 mg) and following 2 weeks of sustained treatment with two different dosage regimens of the drug (120 and 240 mg daily). As compared with placebo, a significant reduction in tremor magnitude was found following a single oral dose but not on sustained administration of the beta-blocker at either dosage. The results suggest that the efficacy of sustained propranolol on isolated or prominent essential head tremor is less predictable and satisfactory than expected on the basis of the single-dose response, as compared with hand tremor.

Reducing Dose Uncertainty for Spot-Scanning Proton Beam Therapy of Moving Tumors by Optimizing the Spot Delivery Sequence

International Nuclear Information System (INIS)

Li, Heng; Zhu, X. Ronald; Zhang, Xiaodong

2015-01-01

Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results: Without delivery sequence optimization, the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns.

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.

Single-dose and multiple-dose pharmacokinetics and dose proportionality of intravenous and intramuscular HPβCD-diclofenac (Dyloject) compared with other diclofenac formulations.

Science.gov (United States)

Mermelstein, Fred; Hamilton, Douglas A; Wright, Curtis; Lacouture, Peter G; Ramaiya, Atulkumar; Carr, Daniel B

2013-10-01

To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. Clinical research center. Healthy adult volunteers. Study 1: Subjects received HPβCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPβCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. Study 1: IV HPβCD-diclofenac had a higher peak plasma concentration (Cmax ) and earlier time to reach maximum plasma concentration (Tmax ), but equivalent plasma exposure (area under the curve from time zero to t [AUC0-t ]) to IV Voltarol. The geometric mean ratio of HPβCD-diclofenac (IV) to Voltarol (IV) for AUC0-t was 106.27%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IM) for AUC0-t was 110.91%. The geometric mean ratio of HPβCD-diclofenac (IV) to HPβCD-diclofenac (IM) for AUC0-t was 101.25%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IV) for AUC0-t was 104.96%. Study 2: Cmax for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPβCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ng·hour/ml) and 37.5 mg (1843 ng·hour/ml) IV HPβCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ng·hour/ml). Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HP�

Single-dose ceftriaxone for chancroid.

Science.gov (United States)

Bowmer, M I; Nsanze, H; D'Costa, L J; Dylewski, J; Fransen, L; Piot, P; Ronald, A R

1987-01-01

Men with genital ulcers that were culture positive for Haemophilus ducreyi were treated with intramuscular ceftriaxone and randomized to three different dose regimens. All but 1 of 50 men treated with 1 g of intramuscular ceftriaxone were cured. Similarly, 0.5 and 0.25 g cured 43 of 44 men and 37 of 38 men, respectively. A single dose of 250 mg of intramuscular ceftriaxone is an effective treatment for chancroid. PMID:3566241

Axioms for behavioural congruence of single-pass instruction sequences

NARCIS (Netherlands)

Bergstra, J.A.; Middelburg, C.A.

2017-01-01

In program algebra, an algebraic theory of single-pass instruction sequences, three congruences on instruction sequences are paid attention to: instruction sequence congruence, structural congruence, and behavioural congruence. Sound and complete axiom systems for the first two congruences were

Effects of local single and fractionated X-ray doses on rat bone marrow blood flow and red blood cell volume

International Nuclear Information System (INIS)

Pitkaenen, M.A.; Hopewell, J.W.

1985-01-01

Time and dose dependent changes in blood flow and red blood cell volume were studied in the locally irradiated bone marrow of the rat femur after single and fractionated doses of X-rays. With the single dose of 10 Gy the bone marrow blood flow although initially reduced returned to the control levels by seven months after irradiation. With doses >=15 Gy the blood flow was still significantly reduced at seven months. The total dose levels predicted by the nominal standard dose equation for treatments in three, six or nine fractions produced approximately the same degree of reduction in the bone marrow blood flow seven months after the irradiation. However, the fall in the red blood cell volume was from 23 to 37% greater in the three fractions groups compared with that in the nine fractions groups. Using the red blood cell volume as a parameter the nominal standard dose formula underestimated the severity of radiation damage in rat bone marrow at seven months for irradiation with small numbers of large dose fractions. (orig.) [de

More than six hundred new families of Newtonian periodic planar collisionless three-body orbits

Science.gov (United States)

Li, XiaoMing; Liao, ShiJun

2017-12-01

The famous three-body problem can be traced back to Isaac Newton in the 1680s. In the 300 years since this "three-body problem" was first recognized, only three families of periodic solutions had been found, until 2013 when Šuvakov and Dmitrašinović [Phys. Rev. Lett. 110, 114301 (2013)] made a breakthrough to numerically find 13 new distinct periodic orbits, which belong to 11 new families of Newtonian planar three-body problem with equal mass and zero angular momentum. In this paper, we numerically obtain 695 families of Newtonian periodic planar collisionless orbits of three-body system with equal mass and zero angular momentum in case of initial conditions with isosceles collinear configuration, including the well-known figure-eight family found by Moore in 1993, the 11 families found by Šuvakov and Dmitrašinović in 2013, and more than 600 new families that have never been reported, to the best of our knowledge. With the definition of the average period T = T/L f, where L f is the length of the so-called "free group element", these 695 families suggest that there should exist the quasi Kepler's third law T* ≈ 2:433 ± 0:075 for the considered case, where T ≈ = T | E|3/2 is the scale-invariant average period and E is its total kinetic and potential energy, respectively. The movies of these 695 periodic orbits in the real space and the corresponding close curves on the "shape sphere" can be found via the website: http://numericaltank.sjtu.edu.cn/three-body/three-body.htm.

Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions

Directory of Open Access Journals (Sweden)

Devarakonda K

2014-08-01

Full Text Available Krishna Devarakonda,1 Terri Morton,1 Rachel Margulis,2 Michael Giuliani,3 Thomas Barrett4 1Clinical Pharmacology and Pharmacokinetics, 2Clinical Operations, 3Research and Development, 4Clinical Affairs, Mallinckrodt Inc., Hazelwood, MO, USA Background: XARTEMIS™ XR (formerly MNK-795 is a combination oxycodone (OC and acetaminophen (APAP analgesic with both immediate-release and extended-release (ER components (ER OC/APAP. The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets versus fasted conditions on the PK of ER OC/APAP was performed. Methods: This Phase I study used an open-label randomized single-dose three-period six-sequence crossover single-center design. Healthy adult participants (n=48 were randomized to receive two tablets of ER OC/APAP under three conditions: following a high-fat meal; following a low-fat meal; and fasted. Plasma concentration versus time data from predose throughout designated times up to 48 hours postdose was used to estimate the PK parameters of oxycodone and APAP. Results: Thirty-one participants completed all three treatment periods. Both oxycodone and APAP were rapidly absorbed under fasted conditions. Total oxycodone and APAP exposures (area under the plasma drug concentration-time curve [AUC] from ER OC/APAP were not significantly affected by food, and minimal changes to maximum observed plasma concentration for oxycodone and APAP were also noted. However, food marginally delayed the time to maximum observed plasma concentration of oxycodone and APAP. There was no indication that tolerability was affected by food. Conclusion: The findings from this study suggest that ER OC

Complete genome sequences of six measles virus strains

NARCIS (Netherlands)

Phan, M.V.T. (My V.T.); C.M.E. Schapendonk (Claudia); B.B. Oude Munnink (Bas B.); M.P.G. Koopmans D.V.M. (Marion); R.L. de Swart (Rik); Cotten, M. (Matthew)

2018-01-01

textabstractGenetic characterization of wild-type measles virus (MV) strains is a critical component of measles surveillance and molecular epidemiology. We have obtained complete genome sequences of six MV strains belonging to different genotypes, using random-primed next generation sequencing.

Stability of methadone hydrochloride in 0.9% sodium chloride injection in single-dose plastic containers.

Science.gov (United States)

Denson, D D; Crews, J C; Grummich, K W; Stirm, E J; Sue, C A

1991-03-01

The stability of methadone hydrochloride in 0.9% sodium chloride injection in flexible polyvinyl chloride containers was studied. Commercially available methadone hydrochloride 20 mg/mL and 25-mL single-dose bags of 0.9% sodium chloride injection were used. Six samples each were prepared at methadone hydrochloride concentrations of 1, 2, and 5 mg/mL. The solutions were stored at room temperature and were not protected from light. Immediately after preparation and after two, three, and four weeks of storage, each of the 18 samples was divided into three aliquots, each of which was analyzed in duplicate for methadone hydrochloride concentration by gas chromatography. There was less than 10% change in methadone hydrochloride concentration in any sample throughout the four-week study period. Methadone hydrochloride at concentrations of 1, 2, and 5 mg/mL prepared in commercially available flexible polyvinyl chloride containers of 0.9% sodium chloride injection and stored at room temperature without deliberate protection from light is stable for at least four weeks.

A Single-Dose, Single-Period Pharmacokinetic Assessment of an Extended-Release Orally Disintegrating Tablet of Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

Science.gov (United States)

Childress, Ann; Newcorn, Jeffrey; Stark, Jeffrey G; McMahen, Russ; Tengler, Mark; Sikes, Carolyn

2016-08-01

To determine the pharmacokinetic (PK) profile of a proprietary formulation of methylphenidate (MPH) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in a phase 1 study. Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) combine two technologies in a single-tablet formulation-an extended-release profile that was designed for once-daily dosing in an ODT that does not require water or chewing for ingestion. This was a single-dose, open-label, single-period, single-treatment study, in which 32 children with ADHD who were receiving MPH in doses of 40 or 60 mg before beginning the study each received a 60-mg dose (2 × 30 mg) of MPH XR-ODT. The following plasma PK parameters of MPH were determined for participants grouped by age (6-7, 8-9, 10-12, and 13-17 years old): maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T½), area under the curve from 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety and tolerability were also assessed. A total of 32 participants received the study drug. For all participants, plasma concentration-time profiles of MPH exhibited a broad peak after administration of MPH XR-ODT through ∼8 hours, indicating extended release from the formulation, followed by an apparent first-order elimination phase. As age increased, MPH exposure decreased and mean estimates of CL/F increased; however, weight-normalized CL/F values were comparable across age groups. Similarly, mean estimates of Vz/F increased with age, but weight-normalization decreased differences across age groups, with the exception of the youngest age group, which had higher values. All adverse events (AEs) were mild. This XR-ODT formulation of MPH demonstrated weight-normalized clearance rates that were consistent across all age groups, a PK profile consistent with once-daily dosing, and an AE profile consistent with

Quantum-Sequencing: Fast electronic single DNA molecule sequencing

Science.gov (United States)

Casamada Ribot, Josep; Chatterjee, Anushree; Nagpal, Prashant

2014-03-01

A major goal of third-generation sequencing technologies is to develop a fast, reliable, enzyme-free, high-throughput and cost-effective, single-molecule sequencing method. Here, we present the first demonstration of unique ``electronic fingerprint'' of all nucleotides (A, G, T, C), with single-molecule DNA sequencing, using Quantum-tunneling Sequencing (Q-Seq) at room temperature. We show that the electronic state of the nucleobases shift depending on the pH, with most distinct states identified at acidic pH. We also demonstrate identification of single nucleotide modifications (methylation here). Using these unique electronic fingerprints (or tunneling data), we report a partial sequence of beta lactamase (bla) gene, which encodes resistance to beta-lactam antibiotics, with over 95% success rate. These results highlight the potential of Q-Seq as a robust technique for next-generation sequencing.

Allergy medication in Japanese volunteers: treatment effect of single doses on nocturnal sleep architecture and next day residual effects.

Science.gov (United States)

Boyle, Julia; Eriksson, Malin; Stanley, Neil; Fujita, Tomoe; Kumagi, Yuji

2006-07-01

To evaluate the acute effects of two histamine H(1)-receptor antagonists on nocturnal sleep architecture and on next day cognitive function and psychomotor performance. This was a single-site, randomized, double-blind, 3-way crossover study, comparing the effects of a single dose of chlorpheniramine (6 mg), fexofenadine (120 mg) and placebo in 18 healthy (male and female) Japanese volunteers aged 20-55 years. Volunteers were resident for 3 days and each period was separated by a minimum 5-day washout period. The three treatments were administered at 23.00 h. Overnight sleep was measured from 23.00 h to 07.00 h using polysomnography. Residual effects were studied at 07.00 h and 9.00 h the next morning, with the latency to sleep (sleep latency test) measured at 09.30 h. Compared with placebo, chlorpheniramine increased the latencies to sleep onset and rapid eye movement (REM) sleep (p < or = 0.05 for both), and reduced the duration of REM sleep (p Six adverse events possibly related to study medication were reported during the study, three of which were related to placebo, two to fexofenadine and one to chlorpheniramine. These findings suggest that a single nocturnal dose of fexofenadine has advantages over the first-generation antihistamine chlorpheniramine, being free of disruption of night-time sleep and detrimental effects on cognitive performance the next day. It is likely that this advantage will remain with chronic ingestion, but this would need to be confirmed.

Developing a single-aliquot protocol for measuring equivalent dose in biogenic carbonates

International Nuclear Information System (INIS)

Stirling, R.J.; Duller, G.A.T.; Roberts, H.M.

2012-01-01

Exploiting biogenic carbonates as thermoluminescence dosimeters requires an understanding of trap kinetics and an appropriate sequence with which to measure equivalent dose. The trap kinetics of two high temperature peaks (peaks II and III) from calcitic snail opercula have been investigated resulting in the calculation of lifetimes of 7.4 × 10 7 and 1.4 × 10 11 years for the two peaks respectively. Two measurement sequences, based upon changes in the application and measurement of a test dose, have been applied to peaks II and III, and though both methods were equally successful in dose recovery and production of a dose response curve some differences were observed. Primarily, the use of method 1 lead to dose dependant sensitivity change implying competition effects occurring during irradiation; method 2 did not experience this phenomenon. As a consequence method 2 was chosen as the most appropriate protocol for single-aliquot dating of this material. When assessing the TL behaviour of the two peaks, peak II performed poorly in dose recovery experiments recovering a dose 60–100% larger than that applied. Disproportionate growth of peak II in response to a beta dose applied prior to measurement, compared to growth following regeneration doses indicated that peak II was not suitable for use in single-aliquot protocols. However, dose recovery results for peak III were all within errors of unity of the given dose, and peak III was therefore chosen as the most appropriate peak for TL dosimetry in these single-aliquot procedures. The lifetime of charge in peak III is sufficient to date over many millions of years, and furthermore using the chosen method 2 the dose response curve has a D 0 of 3,250 ± 163 Gy allowing dating to over 3 million years.

Development and Implementation of a Two-Semester Introductory Organic-Bioorganic Chemistry Sequence: Conclusions from the First Six Years

Science.gov (United States)

Goess, Brian C.

2014-01-01

A two-semester second-year introductory organic chemistry sequence featuring one semester of accelerated organic chemistry followed by one semester of bioorganic chemistry is described. Assessment data collected over a six-year period reveal that such a course sequence can facilitate student mastery of fundamental organic chemistry in the first…

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

Science.gov (United States)

Gammaitoni, Arnold; Smith, Steven; Boyd, Brooks

2018-06-22

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

Single fixed-dose oral dexketoprofen plus tramadol for acute postoperative pain in adults.

Science.gov (United States)

Derry, Sheena; Cooper, Tess E; Phillips, Tudor

2016-09-22

the maximum possible pain relief over six hours, the median time to use of rescue medication, and the proportion of participants requiring rescue medication. We also collected information on adverse events and withdrawals. We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table.We also collected information on the number of participants with at least 50% of the maximum possible pain relief over six hours for dexketoprofen alone and tramadol alone. We included three studies with 1853 participants who had undergone surgical removal of impacted wisdom teeth, hip replacement, or hysterectomy. The overall risk of bias across the three included studies was low, with unclear risk of bias in relation to the size of the three studies. Two studies did not report all our prespecified outcomes, which limited the analyses we could do.The proportion of participants achieving at least 50% pain relief over six hours with dexketoprofen 25 mg plus tramadol 75 mg was 66%, compared to 32% with placebo, giving an NNT of 3.0 (95% CI 2.5 to 3.7) (RR 2.1 (95% CI 1.7 to 2.4); 748 participants; 3 studies) (moderate quality evidence). The response rate with dexketoprofen 25 mg alone was 53% (RR 1.3 (95% CI 1.1 to 1.4); 744 participants; 3 studies) and with tramadol alone was 45% (RR 1.5 (95% CI 1.3 to 1.7); 741 participants; 3 studies) (moderate quality evidence). We downgraded the evidence because of some inconsistency in the results.The median time to use of rescue medication could not be estimated exactly, but was probably eight hours or more, indicating a long duration of effect (moderate quality evidence). We downgraded the evidence because it was not possible to estimate the effect exactly in the two multiple dose studies, resulting in imprecision. Fewer participants used rescue medication with higher doses of active treatment (summary statistic not calculated; 123 participants; 1 study) (very low quality evidence). We downgraded the evidence because

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

Science.gov (United States)

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

2013-10-01

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

Randomized Crossover Comparison of the Short-Term Efficacy and Safety of Single Half-Dose Silodosin and Tamsulosin Hydrochoride in Men With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

Science.gov (United States)

Takeshita, Hideki; Moriyama, Shingo; Arai, Yoshiaki; Washino, Satoshi; Saito, Kimitoshi; Chiba, Koji; Horiuchi, Susumu; Noro, Akira

2016-01-01

To compare the efficacy and safety of single half-dose silodosin and single full-dose tamsulosin in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Japanese men aged ≥50 years with LUTS/BPH and an International Prostate Symptom Score (IPSS) of ≥8 were enrolled in the randomized crossover study and divided into silodosin-preceding (S-T) and tamsulosin-preceding (T-S) groups. The S-T group received 4 mg silodosin once daily for 4 weeks followed by 0.2 mg tamsulosin once daily for 4 weeks. The T-S group received the reverse treatment sequence. A washout period prior to drug crossover was not included. Subjective and objective efficacy parameters including IPSS, quality of life (QOL) index, uroflowmetry, and safety were compared between the two groups. Thirty of 34 men (S-T group n = 16; T-S group n = 14) completed the study. Both drugs significantly improved all IPSS items and QOL index in the first treatment period. Subjective improvement in nocturia by silodosin was observed in both the first and crossover treatment periods. Objective improvement in maximum flow rate by silodosin was only observed in the first treatment period. Adverse events occurred more frequently with silodosin than with tamsulosin; however, none of the adverse events required treatment discontinuation. Ejaculation disorders occurred in three participants (10%) and were associated with silodosin use. Single half-dose silodosin has a similar efficacy to full-dose tamsulosin in Japanese men with LUTS/BPH and thus, may represent an effective, safe, and affordable treatment option. © 2015 Wiley Publishing Asia Pty Ltd.

Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial.

Science.gov (United States)

Wahab, M A; Ali, M E; Rahman, M H; Chowdhury, S A; Monamie, N S; Sultana, N; Khondoker, L

2010-01-01

Tinea (pityriasis) versicolor is a superficial fungal infection and one of the most commonly found pigmentary disorders of skin caused by the yeast Malassezia. Multiple topical as well as systemic therapies are available for treatment. Systemic therapies are used for extensive disease, frequent relapse or where topical agents have failed. The aim that translates the rationale of the study was to compare the efficacy, safety, tolerability and cost effectiveness of single dose 400mg versus 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. A clinical study was done to compare the efficacy of single dose (400 mg) of itraconazole and 7 day 200 mg daily dose of itraconazole in the treatment of extensive tinea versicolor. Total 60 patients (aged 18-50 years) were selected for the study during the period of June 2007 to May 2008 in the department of Dermatology of three different hospitals in Bangladesh. Cases having with extensive involvement, diagnosed clinically and confirmed by wood's lamp and KOH microscopy were taken. Patients were randomly allocated into equal groups. Group A was given single dose 400 mg itraconazole and Group B was given 7 day 200 mg daily itraconazole. Fifty three (88%) male and 7(12%) female were included in the study. The mean age of group A was 32.37+/-9 years and in group B 33.23+/-8 years. The mean duration of the disease in group A was 2.63+/-2 months and 2.76+/-2 months in group B. In group A clinical responders was found cure 22(73.33%) and improvement 5(16.33%) and in group B it was found cure 24(79.99%) and improvement 4(13.33%). The measure at the End point (EP1) equals to 90% response and in-group B it was found cure 24 (79.99%) and improvement 4(13.33%). (Here the End point EP2) equals to 93.33%. The EP clinical analysis however shows 91.66% response. Both single dose and 7 day daily dose of itraconazole can be effective in the treatment of tinea versicolor with extensive involvement but single dose appears

Peculiarities in mice embriogenesis under serotonin effect in pre- and post-irradiation period in prenervous period of development

International Nuclear Information System (INIS)

Konstantinova, M.M.; Panaeva, S.V.; Podmareva, O.N.; Turpaev, T.M.

1995-01-01

Effect of serotonin and X-ray irradiation on mice embriogenesis in prenervous period of development is studied. The above factors were applied separately and in combination (in various doses, with change of sequence). It is shown that development of embriotoxic effect of serotonin is determined by embryos age. Six-day embryos are most sensitive. Eight-day embryos are characterized by absence of toxic effect of serotonin doses applied. The eighth day embryos are most radiosensitive, whereas the six-day ones are less radiosensitive. Serotonin administered to mice females before and after irradiation on the eight day of pregnancy produced radioprotective and therapeutic effect, and on the sixth-seventh days intensified negative radiation consequences. 15 refs.; 2 tabs

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

Science.gov (United States)

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

2013-11-01

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

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

Science.gov (United States)

Lui, Kung-Jong; Chang, Kuang-Chao

2015-01-01

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

Measurement of the equivalent dose in quartz using a regenerative-dose single-aliquot protocol

International Nuclear Information System (INIS)

Murray, A.S.; Roberts, R.G.

1998-01-01

The principles behind a regenerative-dose single-aliquot protocol are outlined. It is shown for three laboratory-bleached Australian sedimentary quartz samples that the relative change in sensitivity of the optically stimulated luminescence (OSL) during a repeated measurement cycle (consisting of a dose followed by a 10 s preheat at a given temperature and then a 100 s exposure to blue/green light at 125 deg. C) is very similar to that of the 110 deg. C thermoluminescence (TL) peak measured during the preheat cycle. The absolute change in the TL sensitivity with preheat temperature is different for samples containing a natural or a regenerative dose. Furthermore, the absolute change in sensitivity in both the OSL and TL signals is non-linear with regeneration cycle, but the relative change in the OSL signal compared to the following 110 deg. C TL measurement is well approximated by a straight line. Both signals are thought to use the same luminescence centres, and so some common behaviour is not unexpected. A new regenerative-dose protocol is presented which makes use of this linear relationship to correct for sensitivity changes with regeneration cycle, and requires only one aliquot for the estimation of the equivalent dose (D e ). The protocol has been applied to quartz from nine Australian sites. To illustrate the value of the regenerative-dose single-aliquot approach, the apparent values of D e for 13 samples, containing doses of between 0.01 and 100 Gy, have been measured at various preheat temperatures of between 160 and 300 deg. C, using a single aliquot for each D e measurement. Excellent agreement is found between these single-aliquot estimates of D e and those obtained from additive-dose multiple-aliquot and single-aliquot protocols, over the entire dose range

An existence proof of a symmetric periodic orbit in the octahedral six-body problem

OpenAIRE

Cavalcanti, Anete Soares

2016-01-01

We present a proof of the existence of a periodic orbit for the Newtonian six-body problem with equal masses. This orbit has three double collisions each period and no multiple collisions. Our proof is based on the minimization of the Lagrangian action functional on a well chosen class of symmetric loops.

Fast, three-dimensional, MR Imaging for polymer gel dosimetric applications involving high dose and steep dose gradients

International Nuclear Information System (INIS)

Sandilos, Panagiotis; Baras, Panagiotis; Georgiou, Evangelos; Dardoufas, Konstantinos; Karaiskos, Pantelis; Papagiannis, Panagiotis; Paschalis, Theodoros; Tatsis, Elias; Torrens, Michael; Vlahos, Lampros

2006-01-01

Polymer gels constitute water equivalent integrating detectors, which, combined with magnetic resonance imaging (MRI), can provide accurate three dimensional (3D) dose distributions in contemporary radiotherapy applications where the small field dimensions and steep dose gradients induce limitations to conventional dosimeters. One of the main obstacles for adapting the method for routine use in the clinical setting is the cost effectiveness of the MRI readout method. Currently, optimized Carr-Purcell-Meiboom-Gill (CPMG) multiple spin echo imaging pulse sequences are commonly used which however result in long imaging times. This work evaluates the efficiency of 3D, dual-echo, k-space segmented turbo spin echo (TSE) scanning sequences for accurate dosimetry with sub-millimetre spatial resolution in strenuous radiation therapy applications. PABIG polymer gel dosimeters were irradiated with an 192 Ir High Dose Rate brachytherapy source, the 4 mm and 8 mm collimator helmets of a gamma knife unit and a custom made x-knife collimator of 1 cm diameter. Profile and dose distribution measurements using TSE are benchmarked against corresponding findings obtained by the commonly used, but time consuming, CPMG sequence as well as treatment planning calculations, Monte Carlo (MC) simulations and film measurements. The implementation of a high Turbo factor was found to provide comparable accuracy, allowing a 64-fold MRI scan acceleration compared to conventional multi-echo sequences. The availability of TSE sequences in typical MRI installations greatly facilitates the introduction of polymer gel dosimetry in the clinical environment as a practicable tool for the determination of full 3D dose distributions in contemporary radiotherapy applications

Fast, three-dimensional, MR Imaging for polymer gel dosimetric applications involving high dose and steep dose gradients

Energy Technology Data Exchange (ETDEWEB)

Sandilos, Panagiotis [Department of Radiology, Medical School, University of Athens, Areteion Hospital, 76 Vas. Sofias Ave., 115 28 Athens (Greece); Baras, Panagiotis [Philips Hellas Medical Systems, 44 Kifissias Ave., Maroussi 151 25, Athens (Greece); Georgiou, Evangelos [Medical Physics Department, University of Athens, 75 Mikras Asias, 115 27 Athens (Greece); Dardoufas, Konstantinos [Department of Radiology, Medical School, University of Athens, Areteion Hospital, 76 Vas. Sofias Ave., 115 28 Athens (Greece): Hygeia Hospital, Kiffisias Avenue and 4 Erythrou Stavrou, Marousi, 151 23 Athens (Greece); Karaiskos, Pantelis [Medical Physics Department, University of Athens, 75 Mikras Asias, 115 27 Athens (Greece): Hygeia Hospital, Kiffisias Avenue and 4 Erythrou Stavrou, Marousi, 151 23 Athens (Greece)]. E-mail: p.karaiskos@hygeia.gr; Papagiannis, Panagiotis [Physics Department, Nuclear and Particle Physics Section, University of Athens, Panepistimioupolis, Ilisia, 157 71 Athens (Greece); Paschalis, Theodoros [Department of Radiology, Medical School, University of Athens, Areteion Hospital, 76 Vas. Sofias Ave., 115 28 Athens (Greece); Tatsis, Elias [Department of Radiology, Medical School, University of Athens, Areteion Hospital, 76 Vas. Sofias Ave., 115 28 Athens (Greece); Torrens, Michael [Hygeia Hospital, Kiffisias Avenue and 4 Erythrou Stavrou, Marousi, 151 23 Athens (Greece); Vlahos, Lampros [Department of Radiology, Medical School, University of Athens, Areteion Hospital, 76 Vas. Sofias Ave., 115 28 Athens (Greece)

2006-12-20

Polymer gels constitute water equivalent integrating detectors, which, combined with magnetic resonance imaging (MRI), can provide accurate three dimensional (3D) dose distributions in contemporary radiotherapy applications where the small field dimensions and steep dose gradients induce limitations to conventional dosimeters. One of the main obstacles for adapting the method for routine use in the clinical setting is the cost effectiveness of the MRI readout method. Currently, optimized Carr-Purcell-Meiboom-Gill (CPMG) multiple spin echo imaging pulse sequences are commonly used which however result in long imaging times. This work evaluates the efficiency of 3D, dual-echo, k-space segmented turbo spin echo (TSE) scanning sequences for accurate dosimetry with sub-millimetre spatial resolution in strenuous radiation therapy applications. PABIG polymer gel dosimeters were irradiated with an {sup 192}Ir High Dose Rate brachytherapy source, the 4 mm and 8 mm collimator helmets of a gamma knife unit and a custom made x-knife collimator of 1 cm diameter. Profile and dose distribution measurements using TSE are benchmarked against corresponding findings obtained by the commonly used, but time consuming, CPMG sequence as well as treatment planning calculations, Monte Carlo (MC) simulations and film measurements. The implementation of a high Turbo factor was found to provide comparable accuracy, allowing a 64-fold MRI scan acceleration compared to conventional multi-echo sequences. The availability of TSE sequences in typical MRI installations greatly facilitates the introduction of polymer gel dosimetry in the clinical environment as a practicable tool for the determination of full 3D dose distributions in contemporary radiotherapy applications.

Design of Long Period Pseudo-Random Sequences from the Addition of -Sequences over

Directory of Open Access Journals (Sweden)

Ren Jian

2004-01-01

Full Text Available Pseudo-random sequence with good correlation property and large linear span is widely used in code division multiple access (CDMA communication systems and cryptology for reliable and secure information transmission. In this paper, sequences with long period, large complexity, balance statistics, and low cross-correlation property are constructed from the addition of -sequences with pairwise-prime linear spans (AMPLS. Using -sequences as building blocks, the proposed method proved to be an efficient and flexible approach to construct long period pseudo-random sequences with desirable properties from short period sequences. Applying the proposed method to , a signal set is constructed.

Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.

Science.gov (United States)

Flanagan, Shawn; Fang, Edward; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

2014-09-01

Tedizolid phosphate is a novel antibacterial under investigation for the treatment of gram-positive infections. This study was conducted to assess the pharmacokinetics, safety, and tolerability of intravenous tedizolid phosphate as well as the oral bioavailability of tedizolid phosphate. Double-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies. Single center in the United States (Covance Clinical Research Unit, Madison, WI) between September 2009 and January 2010. Ninety healthy volunteers. Single intravenous (IV) doses of tedizolid phosphate 50 mg (lead-in) and 100-400 mg. Single oral and IV dose of tedizolid phosphate 200 mg in crossover fashion. Multiple IV doses of tedizolid phosphate 200 and 300 mg for up to 7 days. A dose-dependent increase was observed in the maximum plasma concentration (1.2-5.1 μg/ml) and the area under the concentration-time curve (17.4-58.7 μg × hr/ml) of tedizolid (the microbiologically active moiety of tedizolid phosphate) after single IV doses of tedizolid phosphate 100-400 mg. Administration of IV tedizolid phosphate 200 mg once/day for 7 days resulted in minimal (28%) tedizolid accumulation. The absolute oral bioavailability of tedizolid after a single 200-mg dose of tedizolid phosphate was 91%; pharmacokinetic parameters of tedizolid were similar with oral and IV administration. Treatment-related adverse events occurred in 41% of subjects. Most adverse events were related to infusion site and became more frequent with multiple dosing. In an additional 3-day tolerability study, IV tedizolid phosphate 200 mg and placebo were similarly tolerated, based on visual infusion phlebitis scores. These results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes. © 2014 Cubist Pharmaceuticals. Pharmacotherapy

Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer

Directory of Open Access Journals (Sweden)

Ivelina Gueorguieva

2016-12-01

Full Text Available Objective: Galunisertib (LY2157299 monohydrate, an inhibitor of the transforming growth factor β (TGFβ pathway, is currently under investigation in several clinical trials involving multiple tumor types. The primary objective of this study was to assess relative bioavailability of two new galunisertib formulations developed using the roller compaction (RC dry-milled (RCD and RC slurry-milled (RCS processes, compared with the existing formulation developed using the high-sheer wet granulation (HSWG process. The secondary objective was to report the safety profile after a single dose of the three formulations. Methods: Patients with advanced or metastatic cancer were enrolled into this single-center, 3-period, 6-sequence crossover study. Patients were assigned sequentially to 1 of 6 sequences in blocks of 6 to ensure that all 6 sequences have the same number of completers. A patient entering a sequence received a different galunisertib formulation as a single 150 mg dose orally during each of the 3 periods. Each period was separated from the next by a washout interval of at least 48 hours. Pharmacokinetic (PK parameters, including area under curve (AUC and Cmax, were computed using standard non-compartmentalized methods of analysis. For comparison of exposures between formulations, log-transformed AUC and Cmax values were analyzed using a linear mixed-effects model. Safety assessments included adverse event monitoring, physical examinations, and laboratory tests. Results: Of the 14 patients who entered and completed the study, 13 patients were included in the final statistical analysis. AUC(0-tlast, AUC(0-48 h, and AUC(0-∞ for the RC formulations and the HSWG formulation were similar. Cmax was reduced by approximately 22% and tmax was longer by at least 1.00 h for the RCD and RCS formulations compared with the HSWG formulation. The RC formulations demonstrated a safety profile after a single dose similar to the HSWG formulation. Conclusions

Reduction of construction periods of PWRs by optimization of detailed sequence planning

International Nuclear Information System (INIS)

Stocker, W.; Leverenz, R.

1991-01-01

The construction of PWR's is an enterprise with high investment costs, in total up to three billion US$ and with long construction periods of five years and more. Besides the results reached by the intensive standardization, a further reduction of the construction period is possible by optimization of detailed sequence planning and interfaces of work units. During the execution of the three German Convoy plants ISAR 2, EMSLAND and NECKARWESTHEIM 2, the contractual construction periods were shortened between 4 and 8 months. These reductions were reached after individual investigations by measures like advanced finishing work activities; erection of an increased amount of prefabricated pipings; rearrangement of erection sequences; overlapping of piping erection and electrical installation; reduction of plant commissioning period. All these measures support directly the reduction of the total investment cost of a plant, as already demonstrated by the Convoy plants. (author). 8 figs

Single and 30 fraction tumor control doses correlate in xenografted tumor models: implications for predictive assays

International Nuclear Information System (INIS)

Gerweck, Leo E.; Dubois, Willum; Baumann, Michael; Suit, Herman D.

1995-01-01

Purpose/Objective: In a previous publication we reported that laboratory assays of tumor clonogen number, in combination with intrinsic radiosensitivity measured in-vitro, accurately predicted the rank-order of single fraction 50% tumor control doses, in six rodent and xenografted human tumors. In these studies, tumor hypoxia influenced the absolute value of the tumor control doses across tumor types, but not their rank-order. In the present study we hypothesize that determinants of the single fraction tumor control dose, may also strongly influence the fractionaled tumor control doses, and that knowledge of tumor clonogen number and their sensitivity to fractionated irradiation, may be useful for predicting the relative sensitivity of tumors treated by conventional fractionated irradiation. Methods/Materials: Five tumors of human origin were used for these studies. Special care was taken to ensure that all tumor control dose assays were performed over the same time frame, i.e., in-vitro cells of a similar passage were used to initiate tumor sources which were expanded and used in the 3rd or 4th generation. Thirty fraction tumor control doses were performed in air breathing mice, under normal blood flow conditions (two fractions/day). The results of these studies have been previously published. For studies under uniformly (clamp) hypoxic conditions, tumors arising from the same transplantation were randomized into single or fractionated dose protocols. For estimation of the fractionated TCD50 under hypoxic conditions, tumors were exposed to six 5.4 Gy fractions (∼ 2 Gy equivalent under air), followed by graded 'top-up' dose irradiation for determination of the TCD50; the time interval between doses was 6-9 hours. The single dose equivalent of the six 5.4 Gy doses was used to calculate an extrapolated 30 fraction hypoxic TCD50. Results: Fractionation substantially increased the dose required for tumor control in 4 of the 5 tumors investigated. For these 4 tumors

Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

Science.gov (United States)

Andrade, Roberto; Rodriguez-Barradas, Maria C; Yasukawa, Kosuke; Villarreal, Erick; Ross, Michael; Serpa, Jose A

2017-03-15

Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients. We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period. Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results. When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis. NCT02611765. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Highly multiplexed targeted DNA sequencing from single nuclei.

Science.gov (United States)

Leung, Marco L; Wang, Yong; Kim, Charissa; Gao, Ruli; Jiang, Jerry; Sei, Emi; Navin, Nicholas E

2016-02-01

Single-cell DNA sequencing methods are challenged by poor physical coverage, high technical error rates and low throughput. To address these issues, we developed a single-cell DNA sequencing protocol that combines flow-sorting of single nuclei, time-limited multiple-displacement amplification (MDA), low-input library preparation, DNA barcoding, targeted capture and next-generation sequencing (NGS). This approach represents a major improvement over our previous single nucleus sequencing (SNS) Nature Protocols paper in terms of generating higher-coverage data (>90%), thereby enabling the detection of genome-wide variants in single mammalian cells at base-pair resolution. Furthermore, by pooling 48-96 single-cell libraries together for targeted capture, this approach can be used to sequence many single-cell libraries in parallel in a single reaction. This protocol greatly reduces the cost of single-cell DNA sequencing, and it can be completed in 5-6 d by advanced users. This single-cell DNA sequencing protocol has broad applications for studying rare cells and complex populations in diverse fields of biological research and medicine.

Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

Science.gov (United States)

Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

2017-06-01

The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers.

Science.gov (United States)

Parrillo-Campiglia, Susana; Ercoli, Mónica Cedres; Umpierrez, Ofelia; Rodríguez, Patricia; Márquez, Sara; Guarneri, Carolina; Estevez-Parrillo, Francisco T; Laurenz, Marilena; Estevez-Carrizo, Francisco E

2009-10-01

Imatinib is a tyrosine kinase inhibitor that has been established as a highly effective therapy for chronic myelogenous leukemia and gastrointestinal stromal tumors. A new generic, once-daily 400-mg tablet of imatinib has been developed by a pharmaceutical company in Argentina, where the regulatory standard for marketing authorization of an imatinib generic is in vitro dissolution testing. The aim of this study was to assess the bioequivalence of a new generic film-coated test tablet formulation versus a film-coated reference tablet formulation of imatinib 400 mg. The local manufacturer seeks to validate the in vitro performance of this new formulation with a bioequivalence study. A randomized, open-label, single-dose, fasting, 2-period, 2-sequence crossover design with a 2-week washout period was used in this study. The study population consisted of healthy male South American (Uruguayan) volunteers, who were assigned in a 1:1 ratio to a randomized sequence (test-reference or reference-test). In each period, the test or reference formulation was administered after an overnight fast. During the 72-hour follow-up period, participants were monitored for vital signs and symptoms. Blood samples were collected at 15 time points, including baseline, until 72 hours. Physical examination and laboratory tests (blood, urine) were repeated 1 week after study completion. A noncompartmental model was used to determine the pharmacokinetic parameters of imatinib. The 90% CIs of the test/reference ratios for AUC(0-infinity) and C(max) were determined; the test and reference formulations were considered bioequivalent if the 90% CIs were between 0.80 and 1.25. Adverse events were assessed by a nurse who administered a questionnaire while the healthy volunteers were admitted in the unit. The bioequivalence study was conducted in 30 Uruguayan male volunteers. Demographic characteristics (mean [SD]) included age, 27.8 (6.5) years; weight, 71.2 (9.8) kg; height, 1.71 (0.09) m; and body

Single-dose volume regulation algorithm for a gas-compensated intrathecal infusion pump.

Science.gov (United States)

Nam, Kyoung Won; Kim, Kwang Gi; Sung, Mun Hyun; Choi, Seong Wook; Kim, Dae Hyun; Jo, Yung Ho

2011-01-01

The internal pressures of medication reservoirs of gas-compensated intrathecal medication infusion pumps decrease when medication is discharged, and these discharge-induced pressure drops can decrease the volume of medication discharged. To prevent these reductions, the volumes discharged must be adjusted to maintain the required dosage levels. In this study, the authors developed an automatic control algorithm for an intrathecal infusion pump developed by the Korean National Cancer Center that regulates single-dose volumes. The proposed algorithm estimates the amount of medication remaining and adjusts control parameters automatically to maintain single-dose volumes at predetermined levels. Experimental results demonstrated that the proposed algorithm can regulate mean single-dose volumes with a variation of 98%. © 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Pharmacokinetics of lansoprazole and its main metabolites after single and multiple intravenous doses in healthy Chinese subjects.

Science.gov (United States)

Zhang, Dan; Zhang, Yanan; Liu, Man; Wang, Xiaolin; Yang, Man; Han, Jing; Liu, Huichen

2013-09-01

The aim of the study was to evaluate and compare the pharmacokinetics of lansoprazole (LPZ) and its main metabolites, 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulfone (LPZS), after single and multiple intravenous (i.v.) doses of LPZ in healthy Chinese subjects. Twelve subjects (six males and six females) were given a single dose of LPZ by i.v. infusion on day 1, and multiple doses from day 2 to day 6. Blood samples were collected at designated time points for analysis of plasma concentrations of LPZ, HLPZ and LPZS by an LC-MS/MS method. LPZ was generally well tolerated in healthy Chinese subjects. After single and multiple i.v. doses of 30 mg LPZ, the C max values of LPZ, HLPZ and LPZS were 1490 ± 290 and 1450 ± 280, 175 ± 71 and 154 ± 56, and 51.3 ± 82.9 and 74.1 ± 158.7 ng/mL, with the AUC0-t values 3280 ± 2550 and 4260 ± 3880, 381 ± 128 and 389 ± 111, and 389 ± 1204 and 700 ± 2255 ng h/mL, respectively. The t 1/2 and CL values of LPZ after single and multiple i.v. doses were 1.48 ± 1.03 and 2.19 ± 1.03 h, and 11.67 ± 4.49 and 9.56 ± 4.08 L/h, respectively. Compared with the pharmacokinetics of LPZ after a single dose, t 1/2 increased markedly, CL decreased significantly and AUC increased by over 20 % after multiple doses. The results indicated that there was drug accumulation of LPZ after multiple i.v. doses, and there was no gender-related difference in pharmacokinetics of LPZ and its two metabolites.

Hypokalemic periodic paralysis: Three rare secondary causes

Directory of Open Access Journals (Sweden)

Prasanna Eswaradass Venkatesan

2015-01-01

Full Text Available Periodic paralysis is a rare neuromuscular disorder, related to a defect in muscle ion channels, characterized by episodes of painless muscle weakness, which may be precipitated by heavy exercise, fasting, or high-carbohydrate meals. Hypokalemic periodic paralysis may be familial (primary or secondary. Here, we report three cases of secondary causes of hypokalemic periodic paralysis. On evaluation, case 1 had distal renal tubular acidosis (RTA due to Sjogren′s syndrome, case 2 had drug induced proximal RTA (Fanconi′s syndrome and case 3 had thyrotoxicosis. Clinician must be aware of causes of secondary PP as recognition and diagnosis can completely prevent further attacks of periodic paralysis. Each of the above case is rare, but completely treatable if diagnosed. Low dose steroids with bicarbonate replacement in case 1, stopping tenofovir in case 2 and carbimazole therapy in case 3 prevented further attacks of periodic paralysis and cardiopulmonary complications.

Single-base resolution and long-coverage sequencing based on single-molecule nanomanipulation

International Nuclear Information System (INIS)

An Hongjie; Huang Jiehuan; Lue Ming; Li Xueling; Lue Junhong; Li Haikuo; Zhang Yi; Li Minqian; Hu Jun

2007-01-01

We show new approaches towards a novel single-molecule sequencing strategy which consists of high-resolution positioning isolation of overlapping DNA fragments with atomic force microscopy (AFM), subsequent single-molecule PCR amplification and conventional Sanger sequencing. In this study, a DNA labelling technique was used to guarantee the accuracy in positioning the target DNA. Single-molecule multiplex PCR was carried out to test the contamination. The results showed that the two overlapping DNA fragments isolated by AFM could be successfully sequenced with high quality and perfect contiguity, indicating that single-base resolution and long-coverage sequencing have been achieved simultaneously

A randomized trial of three single - dose radiation therapy regimens in the treatment of metastatic bone pain

International Nuclear Information System (INIS)

Jeremic, Branislav; Shibamoto, Yuta; Acimovic, Ljubisa; Milicic, Biljana; Milisavljevic, Slobodan; Nikolic, Nebojsa; Aleksandrovic, Jasna; Igrutinovic, Ivan

1998-01-01

Purpose: To investigate efficacy of three single dose radiation therapy (RT) regimens in the treatment of painful bone metastasis. Material and Methods: Patient self-assessment by using pain chart enabled evaluation of response to treatment that consisted of either one of the three single fractions of 4 Gy (group I; n = 109), 6 Gy (group II; n = 108), or 8 Gy (group III; n = 110). Results: Patients in groups II and III had higher complete response rate than those in group I, but not significantly, and with no difference between group II and III. However, both patients in group II (73%) and group III (78%) had significantly higher overall response rates when compared to those observed in group I (59%) (I vs II, p = 0.025; I vs III, p = 0.0019), and with no difference between groups II and III (p 0.39). Patients in group III had shortest time to the occurrence of any pain relief which was significantly better than those observed in group I (Welch's t-test, p = 0.012), with no difference between group I and II and group II and III, respectively. There was no difference between the three treatment groups in duration of response and retreatment rate. No effect of histology or metastatic site treated was found. No pathological fractures or spinal cord compressions were observed during the 8 weeks post-RT. Conclusion: Results of this study seem to confirm that 8 Gy could be considered as probably 'lowest' optimal single fraction RT in the treatment of painful bone metastasis, although single fraction RT of 4 Gy should not be easily discarded due to its applicability in specific cases. Since single fraction RT of 6 Gy achieved results not different from that obtained with 8 Gy, further studies are warranted in order to get more informations about 'lowest' optimal single fraction RT in the treatment of painful bone metastasis

Six collapses

International Nuclear Information System (INIS)

Miller, R.H.; Smith, B.F.

1979-01-01

The self-consistent dynamical development of six stellar systems, started from rotating spherical configurations, has been studied by means of a fully three-dimensional n-body integration. The six examples had different initial angular velocities and velocity dispersions. All settled down into prolate bars rotating about a short axis within two initial rotation periods. The bars are long-lived, robust, and stable. Bars are the natural form toward which rapidly rotating stellar dynamical systems develop, instead of the flattened axisymmetric disks that had been expected.The early stages of each collapse are reasonably well described by a theoretical model according to which a collapse passes through a sequence of rigidly rotating, uniform-density spheroids. The first significant departures from spheroidal form were axisymmetric in all cases. Rings formed in some examples, sheets in others, with transition cases between these extremes. Nonaxisymmetry forms developed from these intermediate stages

Complete genome sequences of six strains of the genus methylobacterium

Energy Technology Data Exchange (ETDEWEB)

Marx, Christopher J [Harvard University; Bringel, Francoise O. [University of Strasbourg; Christoserdova, Ludmila [University of Washington, Seattle; Moulin, Lionel [UMR, France; Farhan Ul Haque, Muhammad [CNRS, Strasbourg, France; Fleischman, Darrell E. [Wright State University, Dayton, OH; Gruffaz, Christelle [CNRS, Strasbourg, France; Jourand, Philippe [UMR, France; Knief, Claudia [ETH Zurich, Switzerland; Lee, Ming-Chun [Harvard University; Muller, Emilie E. L. [CNRS, Strasbourg, France; Nadalig, Thierry [CNRS, Strasbourg, France; Peyraud, Remi [ETH Zurich, Switzerland; Roselli, Sandro [CNRS, Strasbourg, France; Russ, Lina [ETH Zurich, Switzerland; Aguero, Fernan [Universidad Nacional de General San Martin; Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Lajus, Aurelie [Genoscope/Centre National de la Recherche Scientifique-Unite Mixte de Recherche; Land, Miriam L [ORNL; Medigue, Claudine [Genoscope/Centre National de la Recherche Scientifique-Unite Mixte de Recherche; Mikhailova, Natalia [U.S. Department of Energy, Joint Genome Institute; Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Stolyar, Sergey [University of Washington; Vorholt, Julia A. [ETH Zurich, Switzerland; Vuilleumier, Stephane [University of Strasbourg

2012-01-01

The complete and assembled genome sequences were determined for six strains of the alphaproteobacterial genus Methylobacterium, chosen for their key adaptations to different plant-associated niches and environmental constraints.

Complete Genome Sequences of Six Strains of the Genus Methylobacterium

Energy Technology Data Exchange (ETDEWEB)

Marx, Christopher J [Harvard University; Bringel, Francoise O. [University of Strasbourg; Christoserdova, Ludmila [University of Washington, Seattle; Moulin, Lionel [UMR, France; UI Hague, Muhammad Farhan [University of Strasbourg; Fleischman, Darrell E. [Wright State University, Dayton, OH; Gruffaz, Christelle [CNRS, Strasbourg, France; Jourand, Philippe [UMR, France; Knief, Claudia [ETH Zurich, Switzerland; Lee, Ming-Chun [Harvard University; Muller, Emilie E. L. [CNRS, Strasbourg, France; Nadalig, Thierry [CNRS, Strasbourg, France; Peyraud, Remi [ETH Zurich, Switzerland; Roselli, Sandro [CNRS, Strasbourg, France; Russ, Lina [ETH Zurich, Switzerland; Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Ivanov, Pavel S. [University of Wyoming, Laramie; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Lajus, Aurelie [Genoscope/Centre National de la Recherche Scientifique-Unite Mixte de Recherche; Land, Miriam L [ORNL; Medigue, Claudine [Genoscope/Centre National de la Recherche Scientifique-Unite Mixte de Recherche; Mikhailova, Natalia [U.S. Department of Energy, Joint Genome Institute; Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Stolyar, Sergey [University of Washington; Vorholt, Julia A. [ETH Zurich, Switzerland; Vuilleumier, Stephane [University of Strasbourg

2012-01-01

The complete and assembled genome sequences were determined for six strains of the alphaproteobacterial genus Methylobacterium, chosen for their key adaptations to different plant-associated niches and environmental constraints.

Effect of single-dose albendazole and vitamin A supplementation on the iron status of pre-school children in Sichuan, China.

Science.gov (United States)

Chen, Ke; Xie, Hu Mina; Tian, Weizheng; Zheng, Xiaoling; Jiang, Alice C

2016-04-01

The aim of this study was to explore the effect of single-dose albendazole and vitamin A intervention on the anaemic status and Fe metabolism of pre-school children. This study was a randomised, placebo-controlled and double-blinded intervention trial. All eligible anaemic pre-school children were randomly divided into three groups: group 1 received no intervention, which served as the control group, group 2 received 400 mg single-dose albendazole administration and group 3 received a 60000 μg vitamin A capsule combined with 400 mg single-dose albendazole at the beginning of the study. The follow-up period was for 6 months. Anthropometry and biochemical index about Fe metabolism were measured before and after intervention. A total of 209 pre-school anaemic children were randomly divided into three intervention groups (sixty-four, sixty-two and sixty for groups 1, 2 and 3, respectively). The mean age of the children in the study was 4·4 (sd 0·7) years and 50·5 % of the children were female (94/186). After a follow-up period of 6 months, the levels of serum retinol, ferritin, transferrin receptor-ferritin index and body total Fe content of children in group 3 were significantly higher compared with children in groups 1 and 2 (PAlbendazole plus vitamin A administration showed more efficacy on the improvement of serum retinol and Fe metabolic status.

Efficacy of Single-Dose and Triple-Dose Albendazole and Mebendazole against Soil-Transmitted Helminths and Taenia spp.: A Randomized Controlled Trial

Science.gov (United States)

Steinmann, Peter; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Jia-Xu; Hattendorf, Jan; Zhou, Hui; Zhou, Xiao-Nong

2011-01-01

Background The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. Methodology/Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. Conclusions/Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are

Can a single dose of human papillomavirus (HPV) vaccine prevent cervical cancer? Early findings from an Indian study.

Science.gov (United States)

Sankaranarayanan, Rengaswamy; Joshi, Smita; Muwonge, Richard; Esmy, Pulikottil Okkuru; Basu, Partha; Prabhu, Priya; Bhatla, Neerja; Nene, Bhagwan M; Shaw, Janmesh; Poli, Usha Rani Reddy; Verma, Yogesh; Zomawia, Eric; Pimple, Sharmila; Tommasino, Massimo; Pawlita, Michael; Gheit, Tarik; Waterboer, Tim; Sehr, Peter; Pillai, Madhavan Radhakrishna

2018-03-15

Human papillomavirus (HPV) vaccination is a major strategy for preventing cervical and other ano-genital cancers. Worldwide HPV vaccination introduction and coverage will be facilitated if a single dose of vaccine is as effective as two or three doses or demonstrates significant protective effect compared to 'no vaccination'. In a multi-centre cluster randomized trial of two vs three doses of quadrivalent HPV vaccination (Gardasil™) in India, suspension of the vaccination due to events unrelated to the study led to per protocol and partial vaccination of unmarried 10-18 year old girls leading to four study groups, two by design and two by default. They were followed up for the primary outcomes of immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity for the vaccine-targeted HPV types and HPV infections. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one dose. One dose recipients demonstrated a robust and sustained immune response against HPV 16 and 18, albeit inferior to that of 3- or 2-doses and the antibody levels were stable over a 4 year period. The frequencies of cumulative incident and persistent HPV 16 and 18 infections up to 7 years of follow-up were similar and uniformly low in all the vaccinated study groups; the frequency of HPV 16 and 18 infections were significantly higher in unvaccinated age-matched control women than among vaccine recipients. The frequency of vaccine non-targeted HPV types was similar in the vaccinated groups but higher in the unvaccinated control women. Our results indicate that a single dose of quadrivalent HPV

The development of rhythmic attending in auditory sequences: attunement, referent period, focal attending.

Science.gov (United States)

Drake, C; Jones, M R; Baruch, C

2000-12-15

This paper is divided into three sections. The first section is theoretical; it extends Dynamic Attending Theory (Jones, M. R. Psychological Review 83 (1976) 323; Jones, M. R. Perception and Psychophysics 41(6) (1987) 631; Jones, M. R. Psychomusicology 9(2) (1990) 193; Jones, M. R., & Boltz, M. Psychological Review 96(3) (1989) 459) to developmental questions concerning tempo and time hierarchies. Generally Dynamic Attending Theory proposes that, when listening to a complex auditory sequence, listeners spontaneously focus on events occurring at an intermediate rate (the referent level), and they then may shift attention to events occurring over longer or shorter time spans, that is at lower (faster) or higher (slower) hierarchical levels (focal attending). The second section of the paper is experimental. It examines maturational changes of three dynamic attending activities involving referent period and level, attunement, and focal attending. Tasks involve both motor tapping (including spontaneous motor tempo and synchronization with simple sequences and music) and tempo discrimination. We compare performances by 4-, 6-, 8-, and 10-year-old children and adults, with or without musical training. Results indicate three changes with increased age and musical training: (1) a slowing of the mean spontaneous tapping rate (a reflection of the referent period) and mean synchronization rate (a reflection of the referent level), (2) enhanced ability to synchronize tapping and discriminate tempo (improved attunement), and (3) an enlarged range of tapping rates towards slower rates and higher hierarchical levels (improved focal attending). A final section considers results in light of the theory proposed here. It is suggested that growth trends can be expressed in terms of listeners' engagement of slower attending oscillators with age and experience, accompanied by the passage from the initial use of a single oscillator towards the coupling of multiple oscillators.

Analysis of the operator action and the single failure criteria in a SGTR sequence using best estimate assumptions with TRACE 5.0

International Nuclear Information System (INIS)

Jimenez, G.; Queral, C.; Rebollo-Mena, M.J.; Martínez-Murillo, J.C.; Lopez-Alonso, E.

2013-01-01

Highlights: ► Several worldwide SGTR deterministic safety analysis methodologies were analyze to study the different assumption made. ► The most relevant assumptions for operation action and single failure criteria are compared through TRACE simulations.► The offsite dose results showed the adequacy of the assumptions included in the analyzed methodologies. ► Two proposal of change for SGTR Emergency Operating Procedure are outlined to minimize the dose in case of a SGTR accident. - Abstract: Steam Generator Tube Rupture (SGTR) sequences in Pressurized Water Reactors are known to be one of the most demanding transients for the operating crew. SGTR are a special kind of transient as they could lead to radiological releases without core damage or containment failure, as they can constitute a direct path from the reactor coolant system to the environment. The first methodology used to perform the Deterministic Safety Analysis (DSA) of a SGTR did not credit the operator action for the first 30 min of the transient, assuming that the operating crew was able to stop the primary to secondary leakage within that period of time. However, the different real SGTR accident cases happened in the USA and over the world demonstrated that the operators usually take more than 30 min to stop the leakage in actual sequences. Some methodologies were raised to overcome that fact, considering operator actions from the beginning of the transient, as it is done in Probabilistic Safety Analysis. This paper presents the results of comparing different assumptions regarding the single failure criteria and the operator action taken from the most common methodologies included in the different Deterministic Safety Analysis. One single failure criteria that has not been analysed previously in the literature is proposed and analysed in this paper too. The comparison is done with a PWR Westinghouse three loop model in TRACE code (Almaraz NPP) with best estimate assumptions but including

Absorbed dose estimates from a single measurement one to three days after the administration of 177Lu-DOTATATE/-TOC.

Science.gov (United States)

Hänscheid, Heribert; Lapa, Constantin; Buck, Andreas K; Lassmann, Michael; Werner, Rudolf A

2017-01-01

To retrospectively analyze the accuracy of absorbed dose estimates from a single measurement of the activity concentrations in tumors and relevant organs one to three days after the administration of 177 Lu-DOTA-TATE/TOC assuming tissue specific effective half-lives. Activity kinetics in 54 kidneys, 30 neuroendocrine tumor lesions, 25 livers, and 27 spleens were deduced from series of planar images in 29 patients. After adaptation of mono- or bi-exponential fit functions to the measured data, it was analyzed for each fit function how precise the time integral can be estimated from fixed tissue-specific half-lives and a single measurement at 24, 48, or 72 h after the administration. For the kidneys, assuming a fixed tissue-specific half-life of 50 h, the deviations of the estimate from the actual integral were median (5 % percentile, 95 % percentile): -3 °% (-15 %>; +16 °%) for measurements after 24 h, +2 %> (-9 %>; +12 %>) for measurements after 48 h, and 0 % (-2 %; +12 %) for measurements after 72 h. The corresponding values for the other tissues, assuming fixed tissue-specific half-lives of 67 h for liver and spleen and 77 h for tumors, were +2 % (-25 %; +20 %) for measurements after 24 h, +2 °% (-16 %>; +17 %>) for measurements after 48 h, and +2 %> (-11 %>; +10 %>) for measurements after 72 h. Especially for the kidneys, which often represent the dose limiting organ, but also for liver, spleen, and neuroendocrine tumors, a meaningful absorbed dose estimate is possible from a single measurement after 2, more preferably 3 days after the administration of 177 Lu-DOTA-TATE/-TOC assuming fixed tissue specific effective half-lives. Schattauer GmbH.

Delivery of adjuvant sequential dose-dense FEC-Doc to patients with breast cancer is feasible, but dose reductions and toxicity are dependent on treatment sequence.

Science.gov (United States)

Wildiers, H; Dirix, L; Neven, P; Prové, A; Clement, P; Squifflet, P; Amant, F; Skacel, T; Paridaens, R

2009-03-01

This study prospectively investigates the impact of dose densification and altering sequence of fluorouracil, epirubicin and cyclophosphamide [FEC(100)] and docetaxel [Doc] on dose delivery and tolerability of adjuvant chemotherapy in breast cancer patients. 117 patients with high-risk primary operable breast cancer were randomized (1:1:2:2) to conventional (three cycles of 3-weekly FEC(100) then three cycles of 3-weekly Doc 100 mg/m(2) or reverse sequence) or dose-dense (dd) treatment (four 10- to 11-day cycles of FEC(75) then four 2-weekly cycles of Doc 75 mg/m(2), or the reverse). In the dd arms, pegfilgrastim was given on day 2 of each cycle, but only as secondary prophylaxis in conventional arms. The primary endpoint was the proportion of patients completing intended cycles at relative dose intensity >or=85% and this was achieved by 95% of patients in each group except for the ddDoc-->FEC group (90%). Dose intensity in the dd arms increased by 48% for FEC and 11% for docetaxel, compared with the conventional arms (both P Doc dose reductions were more frequent with dd treatment and when Doc was given after FEC. Grade 3-4 neutropenia was significantly more frequent with conventional treatment, while fatigue and hand-foot syndrome were numerically more common with dd treatment, particularly when Doc was given after FEC. Discussion Delivery of adjuvant sequential ddFEC and Doc is feasible with growth factor support, and chemotherapy sequence appeared to affect delivery of target doses and toxicity.

Draft Genome Sequences of Six Ruminant Coxiella burnetii Isolates of European Origin

DEFF Research Database (Denmark)

Sidi-Boumedine, Karim; Ellis, Richard J.; Adam, Gilbert

2014-01-01

Coxiella burnetii is responsible for Q fever, a worldwide zoonosis attributed to the inhalation of aerosols contaminated by livestock birth products. Six draft genome sequences of European C. burnetii isolates from ruminants are presented here. The availability of these genomes will help in under......Coxiella burnetii is responsible for Q fever, a worldwide zoonosis attributed to the inhalation of aerosols contaminated by livestock birth products. Six draft genome sequences of European C. burnetii isolates from ruminants are presented here. The availability of these genomes will help...

3D knee segmentation based on three MRI sequences from different planes.

Science.gov (United States)

Zhou, L; Chav, R; Cresson, T; Chartrand, G; de Guise, J

2016-08-01

In clinical practice, knee MRI sequences with 3.5~5 mm slice distance in sagittal, coronal, and axial planes are often requested for the knee examination since its acquisition is faster than high-resolution MRI sequence in a single plane, thereby reducing the probability of motion artifact. In order to take advantage of the three sequences from different planes, a 3D segmentation method based on the combination of three knee models obtained from the three sequences is proposed in this paper. In the method, the sub-segmentation is respectively performed with sagittal, coronal, and axial MRI sequence in the image coordinate system. With each sequence, an initial knee model is hierarchically deformed, and then the three deformed models are mapped to reference coordinate system defined by the DICOM standard and combined to obtain a patient-specific model. The experimental results verified that the three sub-segmentation results can complement each other, and their integration can compensate for the insufficiency of boundary information caused by 3.5~5 mm gap between consecutive slices. Therefore, the obtained patient-specific model is substantially more accurate than each sub-segmentation results.

Improved nonparametric inference for multiple correlated periodic sequences

KAUST Repository

Sun, Ying

2013-08-26

This paper proposes a cross-validation method for estimating the period as well as the values of multiple correlated periodic sequences when data are observed at evenly spaced time points. The period of interest is estimated conditional on the other correlated sequences. An alternative method for period estimation based on Akaike\\'s information criterion is also discussed. The improvement of the period estimation performance is investigated both theoretically and by simulation. We apply the multivariate cross-validation method to the temperature data obtained from multiple ice cores, investigating the periodicity of the El Niño effect. Our methodology is also illustrated by estimating patients\\' cardiac cycle from different physiological signals, including arterial blood pressure, electrocardiography, and fingertip plethysmograph.

Mexico and the food self-sufficiency (six-year period 2006 -2012

Directory of Open Access Journals (Sweden)

Alba Rosa Rivera de la Rosa

2014-01-01

Full Text Available Today, Mexico challenges a globalization trend where richer countries export basic products to developing countries, generating a food crisis that negatively affect the medium-small producers. For this reason, it is important to study the behavior of the food market (exports and imports, since the current Mexican development model does not achieve that food security be a national policy guaranteeing the provision of food for the entire population. Specifically, this article analyses the performance of the food situation during the six–year period 2006-2012, studying three basic foods for Mexican population (maize, bean, wheat and others strategic food like sugar, sorghum and soy. In addition, it analyzes the performance of harvesting and sowing surface, exports and imports. Results indicated that the three main foods showed had high import growth rates decreasing national harvest and sowing surface, with a trade balance deficit during the six-year period studied. The conclusion is that the local producers need a change in the production dynamics and play a strategic role in the food production with new sustainable alternatives.

Pharmacokinetic Effects of Antidrug Antibodies Occurring in Healthy Subjects After a Single Dose of Intravenous Infliximab.

Science.gov (United States)

Ehrenpreis, Eli D

2017-12-01

Infliximab pharmacokinetic studies have been performed in patients receiving chronic infliximab therapy. In these patients, infliximab antidrug antibodies (ADAs) increase infliximab clearance and decrease serum levels and drug efficacy. This study analyzed the pharmacokinetic effect of infliximab ADAs in healthy subjects receiving a single dose of intravenous infliximab. Data were obtained from a single-blind, parallel-group, single-dose study of healthy subjects receiving 5 mg/kg of intravenous SB2 (infliximab biosimilar), EU-sourced Remicade (EU-IFX) or US-sourced Remicade (US-IFX). Serum infliximab was measured at 1, 2, 3, 6, 12, 24, 48, and 72 h and at 5, 7, 14, 21, 28, 42, 56, and 70 days after administration. ADAs were measured pre-dose and at 29 and 71 days. Data from the first ten subjects randomized to each treatment arm were utilized for this study. A two-compartment model of the serum infliximab vs. time curve was developed using nonlinear regression. At 10 weeks, 11 subjects (37%) developed ADAs. ADAs were detected in four subjects after SB2, one subject after EU-IFX, and six subjects after US-IFX infusion. Of these, neutralizing antibodies occurred in one subject after SB2, in no subjects after EU-IFX, and in three subjects after US-IFX infusion. Infliximab clearance was increased in subjects with ADAs vs. those without ADAs (12.89 ± 2.69 vs. 9.90 ± 1.74 ml/h; p ADAs (282.4 ± 56.4 vs. 343.3 ± 61.9 h; p ADAs are common in healthy subjects after a single intravenous dose of infliximab and result in faster infliximab clearance, shorter elimination time, and lower serum infliximab levels. These data confirm that ADAs are common with biologic therapy and significantly impact the efficacy of these drugs.

Effects of a preovulatory single low dose of mifepristone on ovarian function

NARCIS (Netherlands)

van der Stege, Jolande G.; Pahl-van Beest, Elske H.; Beerthuizen, Rob J. C. M.; van Lunsen, Rik H. W.; Scholten, Piet C.; Bogchelman, Dick H.

Objectives To investigate the effect of a single low dose of mifepristone on ovarian function, when administered in the preovulatory period. Methods Healthy women with regular menstrual cycles were studied during two consecutive menstrual cycles. Either mifepristone or placebo was given in a

Response of mouse tongue epithelium to single doses of bleomycin and radiation

International Nuclear Information System (INIS)

Dorr, W.; Hirler, E.; Honig, M.

1993-01-01

Both bleomycin (BLM) and local X-irradiation (25 kV) induce denudation in the tongue epithelium of the C3H-Neuherberg mouse in a dose-dependent manner. In the present study the effect of BLM alone and of combined single doses of drug and radiation were studied using the incidence of epithelial denudation as the end-point. In 'time-line' experiments, 8 mg/kg BLM were given before or after graded doses of X-rays. BLM treatment required a reduction of the radiation dose (ED 50 ) from 15 Gy to 5-7 Gy, independent of sequence or time interval. In contrast, the time course of the response was clearly dependent on the treatment interval. Latency decreased when the drug was injected less than 2 h before irradiation with minimum latency observed at 30 min. Isobologram analysis of experiments with varying combinations of X-rays and BLM demonstrated that small drug doses were relatively more effective than larger doses, suggesting an upward concavity of the BLM dose-effective curve in vivo, i.e. a 'negative shoulder' of the curve in the low dose region. In contrast to the response to X-rays alone, which has a constant latent time to ulcer of 10 days, the latency in combined treatment was clearly shortened with increasing drug dose and at high doses eventually approximated the epithelial turnover time of 5 days. The data suggest that BLM both as a single agent and in combination with X-rays reduced the probability of abortive divisions and through this effect shortened the latent time to epithelial denudation. (author)

Microsatellite DNA fingerprinting, differentiation, and genetic relationships of clones, cultivars, and varieties of six poplar species from three sections of the genus Populus.

Science.gov (United States)

Rahman, Muhammad H; Rajora, Om P

2002-12-01

Accurate identification of Populus clones and cultivars is essential for effective selection, breeding, and genetic resource management programs. The unit of cultivation and breeding in poplars is a clone, and individual cultivars are normally represented by a single clone. Microsatellite DNA markers of 10 simple sequence repeat loci were used for genetic fingerprinting and differentiation of 96 clones/cultivars and varieties belonging to six Populus species (P. deltoides, P. nigra, P. balsamifera, P. trichocarpa, P. grandidentata, and P maximowiczii) from three sections of the genus. All 96 clones/cultivars could be uniquely fingerprinted based on their single- or multilocus microsatellite genotypes. The five P. grandidentata clones could be differentiated based on their single-locus genotypes, while six clones of P. trichocarpa and 11 clones of P. maximowiczii could be identified by their two-locus genotypes. Twenty clones of P. deltoides and 25 clones of P. nigra could be differentiated by their multilocus genotypes employing three loci, and 29 clones of P. balsamifera required the use of multilocus genotypes at five loci for their genetic fingerprinting and differentiation. The loci PTR3, PTR5, and PTR7 were found to be the most informative for genetic fingerprinting and differentiation of the clones. The mean number of alleles per locus ranged from 2.9 in P. trichocarpa or P. grandidentata to 6.0 in P. balsamifera and 11.2 in 96 clones of the six species. The mean number of observed genotypes per locus ranged from 2.4 in P. grandidentata to 7.4 in P. balsamifera and 19.6 in 96 clones of the six species. The mean number of unique genotypes per locus ranged from 1.3 in P. grandidentata to 3.9 in P. deltoides and 8.8 in 96 clones of the six species. The power of discrimination of the microsatellite DNA markers in the 96 clones ranged from 0.726 for PTR4 to 0.939 for PTR7, with a mean of 0.832 over the 10 simple sequence repeat loci. Clones/cultivars from the same

WEB-server for search of a periodicity in amino acid and nucleotide sequences

Science.gov (United States)

E Frenkel, F.; Skryabin, K. G.; Korotkov, E. V.

2017-12-01

A new web server (http://victoria.biengi.ac.ru/splinter/login.php) was designed and developed to search for periodicity in nucleotide and amino acid sequences. The web server operation is based upon a new mathematical method of searching for multiple alignments, which is founded on the position weight matrices optimization, as well as on implementation of the two-dimensional dynamic programming. This approach allows the construction of multiple alignments of the indistinctly similar amino acid and nucleotide sequences that accumulated more than 1.5 substitutions per a single amino acid or a nucleotide without performing the sequences paired comparisons. The article examines the principles of the web server operation and two examples of studying amino acid and nucleotide sequences, as well as information that could be obtained using the web server.

Single dose oral piroxicam for acute postoperative pain

Science.gov (United States)

Moore, R Andrew; Edwards, Jayne; Loke, Yoon; Derry, Sheena; McQuay, Henry J

2014-01-01

Background This is an updated version of the original Cochrane review published in Issue 2, 2000. Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. Objectives To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. Search methods Published studies were identified from systematic searching of MEDLINE, Biological Abstracts, EMBASE, CENTRAL and the Oxford Pain Relief Database in December 2007. Additional studies were identified from the reference lists of retrieved reports. Selection criteria The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult participants, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. Data collection and analysis Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-treat-to-harm (NNH) were calculated. Main results In this update no further studies were found. The original search identified three studies (141 participants) which compared oral piroxicam 20 mg with placebo and

Genomic Sequencing of Single Microbial Cells from Environmental Samples

Energy Technology Data Exchange (ETDEWEB)

Ishoey, Thomas; Woyke, Tanja; Stepanauskas, Ramunas; Novotny, Mark; Lasken, Roger S.

2008-02-01

Recently developed techniques allow genomic DNA sequencing from single microbial cells [Lasken RS: Single-cell genomic sequencing using multiple displacement amplification, Curr Opin Microbiol 2007, 10:510-516]. Here, we focus on research strategies for putting these methods into practice in the laboratory setting. An immediate consequence of single-cell sequencing is that it provides an alternative to culturing organisms as a prerequisite for genomic sequencing. The microgram amounts of DNA required as template are amplified from a single bacterium by a method called multiple displacement amplification (MDA) avoiding the need to grow cells. The ability to sequence DNA from individual cells will likely have an immense impact on microbiology considering the vast numbers of novel organisms, which have been inaccessible unless culture-independent methods could be used. However, special approaches have been necessary to work with amplified DNA. MDA may not recover the entire genome from the single copy present in most bacteria. Also, some sequence rearrangements can occur during the DNA amplification reaction. Over the past two years many research groups have begun to use MDA, and some practical approaches to single-cell sequencing have been developed. We review the consensus that is emerging on optimum methods, reliability of amplified template, and the proper interpretation of 'composite' genomes which result from the necessity of combining data from several single-cell MDA reactions in order to complete the assembly. Preferred laboratory methods are considered on the basis of experience at several large sequencing centers where >70% of genomes are now often recovered from single cells. Methods are reviewed for preparation of bacterial fractions from environmental samples, single-cell isolation, DNA amplification by MDA, and DNA sequencing.

TH-C-BRD-07: Minimizing Dose Uncertainty for Spot Scanning Beam Proton Therapy of Moving Tumor with Optimization of Delivery Sequence

International Nuclear Information System (INIS)

Li, H; Zhang, X; Zhu, X; Li, Y

2014-01-01

Purpose: Intensity modulated proton therapy (IMPT) has been shown to be able to reduce dose to normal tissue compared to intensity modulated photon radio-therapy (IMRT), and has been implemented for selected lung cancer patients. However, respiratory motion-induced dose uncertainty remain one of the major concerns for the radiotherapy of lung cancer, and the utility of IMPT for lung patients was limited because of the proton dose uncertainty induced by motion. Strategies such as repainting and tumor tracking have been proposed and studied but repainting could result in unacceptable long delivery time and tracking is not yet clinically available. We propose a novel delivery strategy for spot scanning proton beam therapy. Method: The effective number of delivery (END) for each spot position in a treatment plan was calculated based on the parameters of the delivery system, including time required for each spot, spot size and energy. The dose uncertainty was then calculated with an analytical formula. The spot delivery sequence was optimized to maximize END and minimize the dose uncertainty. 2D Measurements with a detector array on a 1D moving platform were performed to validate the calculated results. Results: 143 2D measurements on a moving platform were performed for different delivery sequences of a single layer uniform pattern. The measured dose uncertainty is a strong function of the delivery sequence, the worst delivery sequence results in dose error up to 70% while the optimized delivery sequence results in dose error of <5%. END vs. measured dose uncertainty follows the analytical formula. Conclusion: With optimized delivery sequence, it is feasible to minimize the dose uncertainty due to motion in spot scanning proton therapy

Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults.

Science.gov (United States)

Gaskell, Helen; Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

2017-05-25

% pain relief over six hours with the usual dexketoprofen oral dose of 20 mg or 25 mg was 52%, compared to 27% with placebo, giving an NNT of 4.1 (95% CI 3.3 to 5.2) (RR 2.0, 95% CI 1.6 to 2.2; 1177 participants; 8 studies; high quality evidence). Efficacy was significantly better in dental studies (NNT 2.7) than other surgery (NNT 5.7). The proportion of participants using rescue medication within six hours was lower with dexketoprofen (47%) than placebo (69%), giving an NNTp of 4.7 (95% CI 3.3 to 8.0); 445 participants; 5 studies; high quality evidence). Median time to remedication estimates were poorly reported. Reports of any adverse event were similar with dexketoprofen (14%) and placebo (10%) (RR 1.4, 95% CI 0.89 to 2.2; 536 participants, 6 studies; high quality evidence). No study reported any serious adverse events (very low quality evidence). Ketoprofen at doses of 25 mg to 100 mg is an effective analgesic in moderate to severe acute postoperative pain with an NNT for at least 50% pain relief of 2.9 with a 50 mg dose. This is similar to that of commonly used NSAIDs such as ibuprofen (NNT 2.5 for 400 mg dose) and diclofenac (NNT 2.7 for 50 mg dose). Dexketoprofen is also effective with an NNT of 4.1 in the dose range 10 mg to 25 mg. Differential efficacy between dental surgery and other types of surgery seen for both drugs is unusual. Both drugs were well tolerated in single doses.

Overlapping genomic sequences: a treasure trove of single-nucleotide polymorphisms.

Science.gov (United States)

Taillon-Miller, P; Gu, Z; Li, Q; Hillier, L; Kwok, P Y

1998-07-01

An efficient strategy to develop a dense set of single-nucleotide polymorphism (SNP) markers is to take advantage of the human genome sequencing effort currently under way. Our approach is based on the fact that bacterial artificial chromosomes (BACs) and P1-based artificial chromosomes (PACs) used in long-range sequencing projects come from diploid libraries. If the overlapping clones sequenced are from different lineages, one is comparing the sequences from 2 homologous chromosomes in the overlapping region. We have analyzed in detail every SNP identified while sequencing three sets of overlapping clones found on chromosome 5p15.2, 7q21-7q22, and 13q12-13q13. In the 200.6 kb of DNA sequence analyzed in these overlaps, 153 SNPs were identified. Computer analysis for repetitive elements and suitability for STS development yielded 44 STSs containing 68 SNPs for further study. All 68 SNPs were confirmed to be present in at least one of the three (Caucasian, African-American, Hispanic) populations studied. Furthermore, 42 of the SNPs tested (62%) were informative in at least one population, 32 (47%) were informative in two or more populations, and 23 (34%) were informative in all three populations. These results clearly indicate that developing SNP markers from overlapping genomic sequence is highly efficient and cost effective, requiring only the two simple steps of developing STSs around the known SNPs and characterizing them in the appropriate populations.

Dose characteristics of total-skin electron-beam irradiation with six-dual electron fields

International Nuclear Information System (INIS)

Choi, Tae Jin; Kim, Jin Hee; Kim, Ok Bae

1998-01-01

To obtain the uniform dose at limited depth to entire surface of the body, the dose characteristics of degraded electron beam of the large target-skin distance and the dose distribution of the six-dual electron fields were investigated. The experimental dose distributions included the depth dose curve, spatial dose and attenuated electron beam were determined with 300 cm of Target-Skin Distance (TSD) and full collimator size (35x35 cm 2 on TSD 100 cm) in 4 MeV electron beam energy. Actual collimated field size of 105 cmx105 cm at the distance of 300 cm could include entire hemibody. A patient was standing on step board with hands up and holding the pole to stabilize his/her positions for the six-dual fields technique. As a scatter-degrader, 0.5 cm of acrylic plate was inserted at 20 cm from the body surface on the electron beam path to induce ray scattering and to increase the skin dose. The Full Width at Half Maximum(FWHM) of dose profile was 130 cm in large field of 105x105 cm 2 . The width of 100±10% of the resultant dose from two adjacent fields which were separated at 25 cm from field edge for obtaining the dose uniformity was extended to 186 cm. The depth of maximum dose lies at 5 mm and the 80% depth dose lies between 7 and 8 mm for the degraded electron beam by using the 0.5 cm thickness of acrylic absorber. Total skin electron beam irradiation (TSEBI) was carried out using the six dual fields has been developed at Stanford University. The dose distribution in TSEBI showed relatively uniform around the flat region of skin except the protruding and deeply curvatured portion of the body, which showed excess of dose at the former and less dose at the latter. The percent depth dose, profile curves and superimposed dose distribution were investigated using the degraded using the degraded electron beam through the beam absorber. The dose distribution obtained by experiments of TSEBI showed within±10% difference excepts the protruding area of skin which needs a

Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

Directory of Open Access Journals (Sweden)

Cui Y

2013-12-01

Full Text Available Yimin Cui,1 Yan Song,2 Jessie Wang,2 Zhigang Yu,2 Alan Schuster,2 Yu Chen Barrett,2 Charles Frost2 1Peking University First Hospital, Beijing, People's Republic of China; 2Bristol-Myers Squibb, Princeton, NJ, USA Background: The pharmacokinetics (PK, pharmacodynamics (PD, and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods: Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9. The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results: PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion: Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. Keywords: apixaban, oral

Three independent one-dimensional margins for single-fraction frameless stereotactic radiosurgery brain cases using CBCT

International Nuclear Information System (INIS)

Zhang, Qinghui; Chan, Maria F.; Burman, Chandra; Song, Yulin; Zhang, Mutian

2013-01-01

Purpose: Setting a proper margin is crucial for not only delivering the required radiation dose to a target volume, but also reducing the unnecessary radiation to the adjacent organs at risk. This study investigated the independent one-dimensional symmetric and asymmetric margins between the clinical target volume (CTV) and the planning target volume (PTV) for linac-based single-fraction frameless stereotactic radiosurgery (SRS).Methods: The authors assumed a Dirac delta function for the systematic error of a specific machine and a Gaussian function for the residual setup errors. Margin formulas were then derived in details to arrive at a suitable CTV-to-PTV margin for single-fraction frameless SRS. Such a margin ensured that the CTV would receive the prescribed dose in 95% of the patients. To validate our margin formalism, the authors retrospectively analyzed nine patients who were previously treated with noncoplanar conformal beams. Cone-beam computed tomography (CBCT) was used in the patient setup. The isocenter shifts between the CBCT and linac were measured for a Varian Trilogy linear accelerator for three months. For each plan, the authors shifted the isocenter of the plan in each direction by ±3 mm simultaneously to simulate the worst setup scenario. Subsequently, the asymptotic behavior of the CTV V 80% for each patient was studied as the setup error approached the CTV-PTV margin.Results: The authors found that the proper margin for single-fraction frameless SRS cases with brain cancer was about 3 mm for the machine investigated in this study. The isocenter shifts between the CBCT and the linac remained almost constant over a period of three months for this specific machine. This confirmed our assumption that the machine systematic error distribution could be approximated as a delta function. This definition is especially relevant to a single-fraction treatment. The prescribed dose coverage for all the patients investigated was 96.1%± 5.5% with an extreme

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

International Nuclear Information System (INIS)

Storb, R.; Raff, R.F.; Graham, T.; Appelbaum, F.R.; Deeg, H.J.; Schuening, F.G.; Shulman, H.; Pepe, M.

1993-01-01

The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing 60 Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs

Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

Science.gov (United States)

Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

2018-02-01

To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

Design of Long Period Pseudo-Random Sequences from the Addition of m -Sequences over 𝔽 p

Directory of Open Access Journals (Sweden)

Ren Jian

2004-01-01

Full Text Available Pseudo-random sequence with good correlation property and large linear span is widely used in code division multiple access (CDMA communication systems and cryptology for reliable and secure information transmission. In this paper, sequences with long period, large complexity, balance statistics, and low cross-correlation property are constructed from the addition of m -sequences with pairwise-prime linear spans (AMPLS. Using m -sequences as building blocks, the proposed method proved to be an efficient and flexible approach to construct long period pseudo-random sequences with desirable properties from short period sequences. Applying the proposed method to 𝔽 2 , a signal set ( ( 2 n − 1 ( 2 m − 1 , ( 2 n + 1 ( 2 m + 1 , ( 2 ( n + 1 / 2 + 1 ( 2 ( m + 1 / 2 + 1 is constructed.

Spectral sum rules and search for periodicities in DNA sequences

International Nuclear Information System (INIS)

Chechetkin, V.R.

2011-01-01

Periodic patterns play the important regulatory and structural roles in genomic DNA sequences. Commonly, the underlying periodicities should be understood in a broad statistical sense, since the corresponding periodic patterns have been strongly distorted by the random point mutations and insertions/deletions during molecular evolution. The latent periodicities in DNA sequences can be efficiently displayed by Fourier transform. The criteria of significance for observed periodicities are obtained via the comparison versus the counterpart characteristics of the reference random sequences. We show that the restrictions imposed on the significance criteria by the rigorous spectral sum rules can be rationally described with De Finetti distribution. This distribution provides the convenient intermediate asymptotic form between Rayleigh distribution and exact combinatoric theory. - Highlights: → We study the significance criteria for latent periodicities in DNA sequences. → The constraints imposed by sum rules can be described with De Finetti distribution. → It is intermediate between Rayleigh distribution and exact combinatoric theory. → Theory is applicable to the study of correlations between different periodicities. → The approach can be generalized to the arbitrary discrete Fourier transform.

Period variation studies of six contact binaries in M4

Science.gov (United States)

Rukmini, Jagirdar; Shanti Priya, Devarapalli

2018-04-01

We present the first period study of six contact binaries in the closest globular cluster M4 the data collected from June 1995‑June 2009 and Oct 2012‑Sept 2013. New times of minima are determined for all the six variables and eclipse timing (O-C) diagrams along with the quadratic fit are presented. For all the variables, the study of (O-C) variations reveals changes in the periods. In addition, the fundamental parameters for four of the contact binaries obtained using the Wilson-Devinney code (v2003) are presented. Planned observations of these binaries using the 3.6-m Devasthal Optical Telescope (DOT) and the 4-m International Liquid Mirror Telescope (ILMT) operated by the Aryabhatta Research Institute of Observational Sciences (ARIES; Nainital) can throw light on their evolutionary status from long term period variation studies.

Single-dose Rituximab Therapy for Refractory Idiopathic Membranous Nephropathy: A Single-center Experience

OpenAIRE

Katsuno, Takayuki; Ozaki, Takenori; Kim, Hangsoo; Kato, Noritoshi; Suzuki, Yasuhiro; Akiyama, Shinichi; Ishimoto, Takuji; Kosugi, Tomoki; Tsuboi, Naotake; Ito, Yasuhiko; Maruyama, Shoichi

2017-01-01

To date, a recognized treatment for refractory membranous nephropathy (MN) has not been established. Recently, several reports have indicated the efficacy of rituximab as a novel treatment option. However, only a few published accounts exist of rituximab therapy for idiopathic MN (IMN) in the Asian population. We present the cases of three IMN patients who were treated with single-dose rituximab after they showed no response to conventional therapies, including corticosteroids, cyclosporine, ...

Bronchodilator Efficacy of Single Doses of Indacaterol in Japanese Patients with COPD: A Randomised, Double-Blind, Placebo-Controlled Trial

Directory of Open Access Journals (Sweden)

Motokazu Kato

Full Text Available ABSTRACT: Background: Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for the treatment of chronic obstructive pulmonary disease (COPD. This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD. Methods: This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatment periods (washout between periods: 14-28 days. Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 μg or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV1AUC22-24h and safety were assessed for 24 h post-dose in each treatment period. Results: Of the 50 patients randomised (92% male; mean age, 67.2 years, 45 completed the study. Standardised FEV1AUC22-24h was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 μg, respectively (P < 0.001. The improvement in FEV1 was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placebo at all time points. All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo. Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 μg provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations. KEY WORDS: beta2-agonists, bronchodilator, COPD, efficacy, indacaterol

Measurement of the three-dimensional distribution of radiation dose in grid therapy

International Nuclear Information System (INIS)

Trapp, J V; Warrington, A P; Partridge, M; Philps, A; Glees, J; Tait, D; Ahmed, R; Leach, M O; Webb, S

2004-01-01

A single large dose of megavoltage x-rays delivered through a grid is currently being utilized by some centres for palliative radiotherapy treatments of large tumours. In this note, we investigate the dosimetry of grid therapy using two-dimensional film dosimetry and three-dimensional gel dosimetry. It is shown that the radiation dose is attenuated more rapidly with depth in a grid field than an open field, and that even shielded regions receive approximately 25% of the dose to the unshielded areas. (note)

Partial cytochrome b sequences for six Hymenoptera of the eastern United States.

Science.gov (United States)

Collins, A M; Gardner, L M

2001-01-01

Mitochondrial DNA (mtDNA) haplotypes have been commonly used to determine honeybee subspecies relationships. To see if these markers would also be useful for comparisons of other Hymenoptera, we collected workers of six local species: Vespa crabro, the European hornet; Bombus impatiens, a bumblebee; Vespula germanica, the German yellow jacket; Polistes fuscatus, a paper wasp; Halictus ligatus, an alkali bee; and an unspecified Megachile, a leafcutting bee. MtDNA was isolated and digested with six endonucleases (AvaI, BglII, EcoRI, HindIII, HinfI, XbaI). The digested DNA was electrophoresed and visualized on agarose gels with comparison to a standard fragment marker and similarly treated honeybee mtDNA. The fragments obtained were also purified and sequenced. Phylogenetic relationships between six wasp and bee species, Apis mellifera, and several other similar aculeate Hymenoptera were determined. Newly defined DNA sequences were posted to GenBank (AF281169-AF281174).

Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-artemether.

Directory of Open Access Journals (Sweden)

Colin J Sutherland

2005-04-01

Full Text Available Resistance of malaria parasites to chloroquine (CQ and sulphadoxine-pyrimethamine (SP is increasing in prevalence in Africa. Combination therapy can both improve treatment and provide important public health benefits if it curbs the spread of parasites harbouring resistance genes. Thus, drug combinations must be identified which minimise gametocyte emergence in treated cases, and so prevent selective transmission of parasites resistant to any of the partner drugs.In a randomised controlled trial, 497 children with uncomplicated falciparum malaria were treated with CQ and SP (three doses and one dose respectively; n = 91, or six doses of artemether in fixed combination with lumefantrine (co-artemether [Coartem, Riamet] (n = 406. Carriage rates of Plasmodium falciparum gametocytes and trophozoites were measured 7, 14, and 28 d after treatment. The infectiousness of venous blood from 29 children carrying P. falciparum gametocytes 7 d after treatment was tested by membrane-feeding of Anopheles mosquitoes. Children treated with co-artemether were significantly less likely to carry gametocytes within the 4 weeks following treatment than those receiving CQ/SP (30 of 378 [7.94%] versus 42 of 86 [48.8%]; p < 0.0001. Carriers in the co-artemether group harboured gametocytes at significantly lower densities, for shorter periods (0.3 d versus 4.2 d; p < 0.0001 and were less infectious to mosquitoes at day 7 (p < 0.001 than carriers who had received CQ/SP.Co-artemether is highly effective at preventing post-treatment transmission of P. falciparum. Our results suggest that co-artemether has specific activity against immature sequestered gametocytes, and has the capacity to minimise transmission of drug-resistant parasites.

Vaxchora: A Single-Dose Oral Cholera Vaccine.

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Cabrera, Adriana; Lepage, Jayne E; Sullivan, Karyn M; Seed, Sheila M

2017-07-01

To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

Effect of the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan on the pharmacokinetics and pharmacodynamics of a single dose of furosemide.

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Ayalasomayajula, Surya; Schuehly, Uwe; Pal, Parasar; Chen, Fabian; Zhou, Wei; Sunkara, Gangadhar; Langenickel, Thomas H

2018-05-01

Sacubitril/valsartan is indicated for the treatment of heart failure and reduced ejection fraction (HFrEF). Furosemide, a loop diuretic commonly used for the treatment of HFrEF, may be coadministered with sacubitril/valsartan in clinical practice. The effect of sacubitril/valsartan on the pharmacokinetics and pharmacodynamics of furosemide was evaluated in this open label, two-period, single-sequence study in healthy subjects. All subjects (n = 28) received 40 mg oral single-dose furosemide during period 1, followed by a washout of 2 days. In period 2, sacubitril/valsartan 200 mg (97/103 mg) was administered twice daily for 5 days and a single dose of 40 mg furosemide was coadministered on day 6. Serial plasma and urine samples were collected to determine the pharmacokinetics of furosemide and sacubitril/valsartan and the pharmacodynamics of furosemide. The point estimates and the associated 90% confidence intervals for pharmacokinetic parameters were evaluated. Coadministration of furosemide with sacubitril/valsartan decreased the maximum observed plasma concentration (C max ) [estimated geometric mean ratio (90% confidence interval): 0.50 (0.44, 0.56)], area under the plasma concentration-time curve (AUC) from time 0 to infinity [0.72 (0.67, 0.77)] and 24-h urinary excretion of furosemide [0.74 (0.69, 0.79)]. When coadministered with sacubitril/valsartan, 0-4-h, 4-8-h and 0-24-h diuresis in response to furosemide was reduced by ~7%, 21% and 0.2%, respectively, while natriuresis was reduced by ~ 28.5%, 7% and 15%, respectively. Post hoc analysis of the pivotal phase III Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) indicated that the median furosemide dose was similar at baseline and at the end of the study in the sacubitril/valsartan group. Sacubitril/valsartan reduced plasma C max and AUC and 24-h urinary excretion of furosemide, while not significantly affecting its

Single-cell sequencing in stem cell biology.

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Wen, Lu; Tang, Fuchou

2016-04-15

Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.

Strain-specific and pooled genome sequences for populations of Drosophila melanogaster from three continents.

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Bergman, Casey M; Haddrill, Penelope R

2015-01-01

To contribute to our general understanding of the evolutionary forces that shape variation in genome sequences in nature, we have sequenced genomes from 50 isofemale lines and six pooled samples from populations of Drosophila melanogaster on three continents. Analysis of raw and reference-mapped reads indicates the quality of these genomic sequence data is very high. Comparison of the predicted and experimentally-determined Wolbachia infection status of these samples suggests that strain or sample swaps are unlikely to have occurred in the generation of these data. Genome sequences are freely available in the European Nucleotide Archive under accession ERP009059. Isofemale lines can be obtained from the Drosophila Species Stock Center.

Treatment of chronic spontaneous urticaria with a single dose of omalizumab: A study of four cases

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Radhakrishnan Subramaniyan

2016-01-01

Full Text Available Background: Chronic spontaneous urticaria (CSU has a detrimental effect on patients′ emotional and physical quality of life. Omalizumab, an anti-immunoglobulin E humanized monoclonal antibody, has been shown to be very effective in the treatment of refractory chronic urticaria patients but may not be an economically viable option for all CSU patients. However, we present a case series where a single dose of omalizumab gave sustained relief of symptoms in patients with CSU, which may be an economical option. Aims: The aim of this study is to assess the efficacy of a single dose of omalizumab in the treatment of CSU. Materials and Methods: Four patients of CSU whose disease was not controlled with four times the licensed dose of tablet fexofenadine 180 mg were exhibited one subcutaneous injection of omalizumab and were followed up at 4 weekly intervals for 24 weeks for Weekly Urticaria Activity Score 7 (UAS7 and Dermatology Life Quality Index (DLQI. Results: A sharp decline in UAS7 and DLQI was documented in 7-10 days. The decline was maintained up to 16 weeks in one case and 20 weeks in the other three cases. Both the scores at the end of the follow-up period of 24 weeks were better than the pre-omalizumab scores. Conclusion: The results of this case series indicate the efficacy of a single-dose omalizumab in treating moderate to severe refractory CSU. Further studies are required to identify the minimum frequency of administering omalizumab to effectively control CSU. This would greatly reduce the cost of this novel therapy.

Effects of Colored Noise on Periodic Orbits in a One-Dimensional Map

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Li, Feng-Guo; Ai, Bao-Quan

2011-06-01

Noise can induce inverse period-doubling transition and chaos. The effects of the colored noise on periodic orbits, of the different periodic sequences in the logistic map, are investigated. It is found that the dynamical behaviors of the orbits, induced by an exponentially correlated colored noise, are different in the mergence of transition, and the effects of the noise intensity on their dynamical behaviors are different from the effects of the correlation time of noise. Remarkably, the noise can induce new periodic orbits, namely, two new orbits emerge in the period-four sequence at the bifurcation parameter value μ = 3.5, four new orbits in the period-eight sequence at μ = 3.55, and three new orbits in the period-six sequence at μ = 3.846, respectively. Moreover, the dynamical behaviors of the new orbits clearly show the resonancelike response to the colored noise.

Effects of Colored Noise on Periodic Orbits in a One-Dimensional Map

International Nuclear Information System (INIS)

Li Fengguo; Ai Baoquan

2011-01-01

Noise can induce inverse period-doubling transition and chaos. The effects of the colored noise on periodic orbits, of the different periodic sequences in the logistic map, are investigated. It is found that the dynamical behaviors of the orbits, induced by an exponentially correlated colored noise, are different in the mergence of transition, and the effects of the noise intensity on their dynamical behaviors are different from the effects of the correlation time of noise. Remarkably, the noise can induce new periodic orbits, namely, two new orbits emerge in the period-four sequence at the bifurcation parameter value μ = 3.5, four new orbits in the period-eight sequence at μ = 3.55, and three new orbits in the period-six sequence at μ = 3.846, respectively. Moreover, the dynamical behaviors of the new orbits clearly show the resonancelike response to the colored noise. (general)

Evaluation of the influence of weather conditions on external dose rate

International Nuclear Information System (INIS)

Knight, A.

1993-01-01

Six time periods in 1989/90, when there were high gamma ray dose rate readings at three or more RIMNET Phase 1 sites, were selected for detailed study. The high dose rates were compared with meteorological data (rainfall, temperatures, windspeeds and atmospheric pressure) at the sites for the time periods studied. The results using daily and hourly data clearly show a correlation between gamma ray dose rate and rainfall but not with the other meteorological parameters studied. The increase in dose rate with increased rainfall is believed to be due to radon decay products being washed down with heavy rain. (author)

Protein secondary structure prediction for a single-sequence using hidden semi-Markov models

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Borodovsky Mark

2006-03-01

Full Text Available Abstract Background The accuracy of protein secondary structure prediction has been improving steadily towards the 88% estimated theoretical limit. There are two types of prediction algorithms: Single-sequence prediction algorithms imply that information about other (homologous proteins is not available, while algorithms of the second type imply that information about homologous proteins is available, and use it intensively. The single-sequence algorithms could make an important contribution to studies of proteins with no detected homologs, however the accuracy of protein secondary structure prediction from a single-sequence is not as high as when the additional evolutionary information is present. Results In this paper, we further refine and extend the hidden semi-Markov model (HSMM initially considered in the BSPSS algorithm. We introduce an improved residue dependency model by considering the patterns of statistically significant amino acid correlation at structural segment borders. We also derive models that specialize on different sections of the dependency structure and incorporate them into HSMM. In addition, we implement an iterative training method to refine estimates of HSMM parameters. The three-state-per-residue accuracy and other accuracy measures of the new method, IPSSP, are shown to be comparable or better than ones for BSPSS as well as for PSIPRED, tested under the single-sequence condition. Conclusions We have shown that new dependency models and training methods bring further improvements to single-sequence protein secondary structure prediction. The results are obtained under cross-validation conditions using a dataset with no pair of sequences having significant sequence similarity. As new sequences are added to the database it is possible to augment the dependency structure and obtain even higher accuracy. Current and future advances should contribute to the improvement of function prediction for orphan proteins inscrutable

Tolerance of the human spinal cord to single dose radiosurgery

International Nuclear Information System (INIS)

Ryu, S.; Zhu, G.; Yin, F.-F.; Ajlouni, M.; Kim, J.H.

2003-01-01

Tolerance of the spinal cord to the single dose of radiation is not well defined. Although there are cases of human spinal cord tolerance from re-irradiation to the same cord level, the information about the tolerance of human spinal cord to single large dose of radiosurgery is not available. We carried out spinal radiosurgery to treat spinal metastasis and studied the single dose tolerance of the human spinal cord in an ongoing dose escalation paradigm. A total of 39 patients with 48 lesions of spinal metastasis were treated with single dose radiosurgery at Henry Ford Hospital. The radiosurgery dose was escalated from 8 Gy to 16 Gy at 2 Gy increment. The radiation dose was prescribed to periphery of the spinal tumor. The radiation dose to the spinal cord was estimated by computerized dosimetry. The median follow-up time was 10 months (range 6-18 months) from the radiosurgery. The endpoint of the study was to demonstrate the efficacy of the spinal radiosurgery and to determine the tolerance of human spinal cord to single dose radiosurgery. The dose to the spinal cord was generally less than 50 % of the prescribed radiation dose. The volume of the spinal cord that received higher than this dose was less than 20 % of the anterior portion of the spinal cord. Maximum single dose of 8 Gy was delivered to the anterior 20 % of the spinal cord in this dose escalation study. The dose volume histogram will be presented. There was no acute or subacute radiation toxicity detected clinically and radiologically during the maximum follow-up of 20 months. Further dose escalation is in progress. The single tolerance dose of the human spinal cord appears to be at least 8 Gy when it was given to the 20 % of the cord volume, although the duration of follow up is not long enough to detect severe late cord toxicity. This study offers a valuable radiobiological basis of the normal spinal cord tolerance, and opens spinal radiosurgery as a safe treatment for spinal metastasis

Evaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers.

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Bai, Stephen A; Xiang, Qinfang; Finn, Andrew

2016-02-01

Buprenorphine, a partial μ-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. Both studies enrolled healthy volunteers, aged 18 to 55 years, who received concurrent oral naltrexone to reduce adverse events (AEs); subjects with a history or evidence of substance abuse or current use of any product affecting cytochrome P450 3A4 activity were excluded. The first study (n = 25) was a 5-period crossover trial with 4 single doses (75 and 300 and 300 and 1200 μg) of 2 formulations (F14 and F24) of buccal buprenorphine (BBUP) and a 300-μg intravenous dose of buprenorphine with a 7-day washout between periods. In the second study, each subject (n = 10) received 6 doses of 4 BBUP strengths (60, 120, 180, and 240 μg BID) in a dose-escalation design. Plasma concentrations of buprenorphine and norbuprenorphine were assayed, and pharmacokinetics were summarized with descriptive statistics and analyzed by using a linear mixed effects model (single-dose study). AEs were recorded. In the single-dose study, the 2 formulations exhibited comparable bioavailability of 46% to 51% that was independent of dose, with a single buprenorphine peak concentration from each BBUP dose occurring at 2.5 to 3 hours. The mean buprenorphine Cmax across the doses ranged from 0.17 ng/mL for the 75-µg dose to 1.43 ng/mL for the 1200-µg dose. AUC0-∞, AUC0-last, and Cmax were proportional to the dose of BBUP administered. Cmax of norbuprenorphine after BBUP administration was approximately one tenth that of buprenorphine Cmax. In the multiple-dose study, steady state was reached within 3 days of BID dosing. There was a linear increase in exposure across the dose range from 60 to 240 μg BID. Treatment-emergent AEs in both studies were consistent with those reported with opiate administration to

Evaluation of six TPS algorithms in computing entrance and exit doses

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Metwaly, Mohamed; Glegg, Martin; Baggarley, Shaun P.; Elliott, Alex

2014-01-01

Entrance and exit doses are commonly measured in in vivo dosimetry for comparison with expected values, usually generated by the treatment planning system (TPS), to verify accuracy of treatment delivery. This report aims to evaluate the accuracy of six TPS algorithms in computing entrance and exit doses for a 6 MV beam. The algorithms tested were: pencil beam convolution (Eclipse PBC), analytical anisotropic algorithm (Eclipse AAA), AcurosXB (Eclipse AXB), FFT convolution (XiO Convolution), multigrid superposition (XiO Superposition), and Monte Carlo photon (Monaco MC). Measurements with ionization chamber (IC) and diode detector in water phantoms were used as a reference. Comparisons were done in terms of central axis point dose, 1D relative profiles, and 2D absolute gamma analysis. Entrance doses computed by all TPS algorithms agreed to within 2% of the measured values. Exit doses computed by XiO Convolution, XiO Superposition, Eclipse AXB, and Monaco MC agreed with the IC measured doses to within 2%‐3%. Meanwhile, Eclipse PBC and Eclipse AAA computed exit doses were higher than the IC measured doses by up to 5.3% and 4.8%, respectively. Both algorithms assume that full backscatter exists even at the exit level, leading to an overestimation of exit doses. Despite good agreements at the central axis for Eclipse AXB and Monaco MC, 1D relative comparisons showed profiles mismatched at depths beyond 11.5 cm. Overall, the 2D absolute gamma (3%/3 mm) pass rates were better for Monaco MC, while Eclipse AXB failed mostly at the outer 20% of the field area. The findings of this study serve as a useful baseline for the implementation of entrance and exit in vivo dosimetry in clinical departments utilizing any of these six common TPS algorithms for reference comparison. PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.N‐, 87.53.Bn PMID:24892349

Overlapping Genomic Sequences: A Treasure Trove of Single-Nucleotide Polymorphisms

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Taillon-Miller, Patricia; Gu, Zhijie; Li, Qun; Hillier, LaDeana; Kwok, Pui-Yan

1998-01-01

An efficient strategy to develop a dense set of single-nucleotide polymorphism (SNP) markers is to take advantage of the human genome sequencing effort currently under way. Our approach is based on the fact that bacterial artificial chromosomes (BACs) and P1-based artificial chromosomes (PACs) used in long-range sequencing projects come from diploid libraries. If the overlapping clones sequenced are from different lineages, one is comparing the sequences from 2 homologous chromosomes in the overlapping region. We have analyzed in detail every SNP identified while sequencing three sets of overlapping clones found on chromosome 5p15.2, 7q21–7q22, and 13q12–13q13. In the 200.6 kb of DNA sequence analyzed in these overlaps, 153 SNPs were identified. Computer analysis for repetitive elements and suitability for STS development yielded 44 STSs containing 68 SNPs for further study. All 68 SNPs were confirmed to be present in at least one of the three (Caucasian, African-American, Hispanic) populations studied. Furthermore, 42 of the SNPs tested (62%) were informative in at least one population, 32 (47%) were informative in two or more populations, and 23 (34%) were informative in all three populations. These results clearly indicate that developing SNP markers from overlapping genomic sequence is highly efficient and cost effective, requiring only the two simple steps of developing STSs around the known SNPs and characterizing them in the appropriate populations. [The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AC003015 (for GS113423), AC002380 (GS330J10), AC000066 (RG293F11), AC003086 (RG104F04), AC002525 (257C22A), and U73331 (96A18A).] PMID:9685323

Blood phenylalanine concentrations in patients with PAH-deficient hyperphenylalaninaemia off diet without and with three different single oral doses of tetrahydrobiopterin: assessing responsiveness in a model of statistical process control.

Science.gov (United States)

Lindner, M; Gramer, G; Garbade, S F; Burgard, P

2009-08-01

Tetrahydrobiopterin (BH(4)) cofactor loading is a standard procedure to differentiate defects of BH(4) metabolism from phenylalanine hydroxylase (PAH) deficiency. BH(4) responsiveness also exists in PAH-deficient patients with high residual PAH activity. Unexpectedly, single cases with presumed nil residual PAH activity have been reported to be BH(4) responsive, too. BH(4) responsiveness has been defined either by a >or=30% reduction of blood Phe concentration after a single BH(4) dose or by a decline greater than the individual circadian Phe level variation. Since both methods have methodological disadvantages, we present a model of statistical process control (SPC) to assess BH(4) responsiveness. Phe levels in 17 adult PKU patients of three phenotypic groups off diet were compared without and with three different single oral dosages of BH(4) applied in a double-blind randomized cross-over design. Results are compared for >or=30% reduction and SPC. The effect of BH(4) by >or=30% reduction was significant for groups (p < 0.01) but not for dose (p = 0.064), with no interaction of group with dose (p = 0.24). SPC revealed significant effects for group (p < 0.01) and the interaction for group with dose (p < 0.05) but not for dose alone (p = 0.87). After one or more loadings, seven patients would be judged to be BH(4) responsive either by the 30% criterion or by the SPC model, but only three by both. Results for patients with identical PAH genotype were not very consistent within (for different BH(4) doses) and between the two models. We conclude that a comparison of protein loadings without and with BH(4) combined with a standardized procedure for data analysis and decision would increase the reliability of diagnostic results.

A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab.

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Kaur, Primal; Chow, Vincent; Zhang, Nan; Moxness, Michael; Kaliyaperumal, Arunan; Markus, Richard

2017-03-01

To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501. Randomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC inf ) and the maximum observed concentration (C max ). Secondary end points included safety and immunogenicity. AUC inf and C max were similar across the three groups. Geometrical mean ratio (GMR) of AUC inf was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of C max was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUC inf and C max were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups. Results of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups. EudraCT number 2012-000785-37; Results. 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/.

Single- and multiple-dose pharmacokinetics of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155 compared with immediate-release hydrocodone bitartrate/ibuprofen and immediate-release tramadol HCl/acetaminophen

Directory of Open Access Journals (Sweden)

Devarakonda K

2015-09-01

Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young41Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, 2Mallinckrodt Pharmaceuticals, 3Research and Development, Mallinckrodt Pharmaceuticals, 4Department of Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USAObjective: To characterize the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (IR/ER HB/APAP, IR HB/ibuprofen, and IR tramadol HCl/APAP.Methods: In this single-center, open-label, randomized, four-period crossover study, healthy participants received four treatments under fasted conditions: 1 a single dose of two IR/ER HB/APAP 7.5/325 mg tablets (15/650 mg total dose on day 1, followed by two tablets every 12 hours (q12h beginning on day 3; 2 a single dose of IR HB/ibuprofen 15/400 mg (divided as one 7.5/200 mg tablet at hour 0 and 6, followed by one tablet every 6 hours (q6h beginning on day 3; 3 a single dose of IR tramadol HCl/APAP 75/650 mg (divided as one 37.5/325 mg tablet at hour 0 and 6, followed by one tablet q6h beginning on day 3; and 4 a single dose of three IR/ER HB/APAP 7.5/325 mg tablets (22.5/975 mg total dose on day 1, a three-tablet initial dose at 48 hours followed by two-tablet doses q12h beginning on day 3. Hydrocodone and APAP single-dose and steady-state PK were assessed. Adverse events were monitored.Results: The PK analysis was carried out on 29 of 48 enrolled participants who completed all treatment periods. Single-dose hydrocodone exposure was similar for IR/ER HB/APAP 22.5/975 mg and IR HB/ibuprofen 15/400 mg; time to maximum observed plasma concentration was shorter and half-life was longer for IR/ER HB/APAP (22.5/975 mg and 15/650 mg vs IR HB/ibuprofen. Single-dose APAP exposure was similar for IR/ER HB/APAP 15/650 mg and IR tramadol HCl/APAP 75/650 mg. Steady-state hydrocodone and APAP exposures

Single toxin dose-response models revisited

Energy Technology Data Exchange (ETDEWEB)

Demidenko, Eugene, E-mail: eugened@dartmouth.edu [Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH03756 (United States); Glaholt, SP, E-mail: sglaholt@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States); Kyker-Snowman, E, E-mail: ek2002@wildcats.unh.edu [Department of Natural Resources and the Environment, University of New Hampshire, Durham, NH03824 (United States); Shaw, JR, E-mail: joeshaw@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Chen, CY, E-mail: Celia.Y.Chen@dartmouth.edu [Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States)

2017-01-01

The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the four models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.

Three-dimensional conformal pancreas treatment: comparison of four- to six-field techniques

International Nuclear Information System (INIS)

Higgins, Patrick D.; Sohn, Jason W.; Fine, Robert M.; Schell, Michael C.

1995-01-01

Purpose: We compare practical conformal treatment approaches to pancreatic cancer using 6 and 18 MV photons and contrast those approaches against standard techniques. Methods and Materials: A four-field conformal technique for treating pancreas cancer has been developed using nonopposed 18 MV photons. This approach has been extended to 6 MV photon application by the addition of one to two fields. These techniques have been optimized to increase sparing of normal liver and bowel, compared with opposed-field methods, to improve patient tolerance of high doses. In this study we compare these techniques in a simulated tumor model in a cylindrical phantom. Dose-volume analysis is used to quantify differences between the conformal, nonopposed techniques with conformal, opposed field methods. This model is also used to evaluate the effect of 1-2 cm setup errors on dose-volume coverage. Results: Dose-volume analysis demonstrates that five-to-six field conformal treatments using 6 MV photons provides similar or better dose coverage and normal tissue sparing characteristics as an optimized 18 MV, four-field approach when 1-2 cm margins are included for setup uncertainty. All approaches using nonopposed beam geometry provide significant reduction in the volume of tissue encompassed by the 30-50% isodose surfaces, as compared with four-field box techniques. Conclusions: Three-dimensional (3D) conformal treatments can be designed that significantly improve dose-volume characteristics over conventional treatment designs without costing unacceptable amounts of machine time. Further, deep intraabdominal sites can be adequately accessed and treated on intermediate energy machines with a relatively moderate increase in machine time

Massively parallel whole genome amplification for single-cell sequencing using droplet microfluidics.

Science.gov (United States)

Hosokawa, Masahito; Nishikawa, Yohei; Kogawa, Masato; Takeyama, Haruko

2017-07-12

Massively parallel single-cell genome sequencing is required to further understand genetic diversities in complex biological systems. Whole genome amplification (WGA) is the first step for single-cell sequencing, but its throughput and accuracy are insufficient in conventional reaction platforms. Here, we introduce single droplet multiple displacement amplification (sd-MDA), a method that enables massively parallel amplification of single cell genomes while maintaining sequence accuracy and specificity. Tens of thousands of single cells are compartmentalized in millions of picoliter droplets and then subjected to lysis and WGA by passive droplet fusion in microfluidic channels. Because single cells are isolated in compartments, their genomes are amplified to saturation without contamination. This enables the high-throughput acquisition of contamination-free and cell specific sequence reads from single cells (21,000 single-cells/h), resulting in enhancement of the sequence data quality compared to conventional methods. This method allowed WGA of both single bacterial cells and human cancer cells. The obtained sequencing coverage rivals those of conventional techniques with superior sequence quality. In addition, we also demonstrate de novo assembly of uncultured soil bacteria and obtain draft genomes from single cell sequencing. This sd-MDA is promising for flexible and scalable use in single-cell sequencing.

Comparative analyses of six solanaceous transcriptomes reveal a high degree of sequence conservation and species-specific transcripts

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Ouyang Shu

2005-09-01

Full Text Available Abstract Background The Solanaceae is a family of closely related species with diverse phenotypes that have been exploited for agronomic purposes. Previous studies involving a small number of genes suggested sequence conservation across the Solanaceae. The availability of large collections of Expressed Sequence Tags (ESTs for the Solanaceae now provides the opportunity to assess sequence conservation and divergence on a genomic scale. Results All available ESTs and Expressed Transcripts (ETs, 449,224 sequences for six Solanaceae species (potato, tomato, pepper, petunia, tobacco and Nicotiana benthamiana, were clustered and assembled into gene indices. Examination of gene ontologies revealed that the transcripts within the gene indices encode a similar suite of biological processes. Although the ESTs and ETs were derived from a variety of tissues, 55–81% of the sequences had significant similarity at the nucleotide level with sequences among the six species. Putative orthologs could be identified for 28–58% of the sequences. This high degree of sequence conservation was supported by expression profiling using heterologous hybridizations to potato cDNA arrays that showed similar expression patterns in mature leaves for all six solanaceous species. 16–19% of the transcripts within the six Solanaceae gene indices did not have matches among Solanaceae, Arabidopsis, rice or 21 other plant gene indices. Conclusion Results from this genome scale analysis confirmed a high level of sequence conservation at the nucleotide level of the coding sequence among Solanaceae. Additionally, the results indicated that part of the Solanaceae transcriptome is likely to be unique for each species.

Single-phase DECT with VNCT compared with three-phase CTU in patients with haematuria

Energy Technology Data Exchange (ETDEWEB)

Park, Jung Jae; Park, Byung Kwan; Kim, Chan Kyo [Sungkyunkwan University School of Medicine, Department of Radiology, Samsung Medical Center, Seoul (Korea, Republic of)

2016-10-15

To retrospectively evaluate the diagnostic performance of single-phase dual-energy CT (DECT) with virtual non-contrast CT (VNCT) compared with three-phase CT urography (CTU) in patients with haematuria. A total of 296 patients underwent three-phase CTU (NCT at 120 kVp; nephrographic phase and excretory phase DECTs at 140 kVp and 80 kVp) owing to haematuria. Diagnostic performances of CT scans were compared for detecting urothelial tumours and urinary stones. Dose-length product (DLP) was compared in relation to single-phase DECT and three-phase CTU Dose-length product (DLP) was compared in relation to single-phase DECT and three-phase CTU. Sensitivity and specificity for tumour were 95 % (19/20) and 98.9 % (273/276) on CTU, 95 % (19/20) and 98.2 % (271/276) on nephrographic phase DECT, and 90 % (18/20) and 98.2 % (271/276) on excretory phase DECT (P > 0.1). Of the 148 stones detected on NCT, 108 (73 %) and 100 (67.6 %) were detected on nephrographic phase and excretory phase VNCTs, respectively. The mean size of stones undetected on nephrographic and excretory VNCTs was measured as 1.5 ± 0.5 mm and 1.6 ± 0.6 mm, respectively. The mean DLPs of three-phase CTU, nephrographic phase DECT and excretory phase DECT were 1076 ± 248 mGy . cm, 410 ± 98 mGy . cm, and 360 ± 87 mGy . cm, respectively (P < 0.001). Single-phase DECT has a potential to replace three-phase CTU for detecting tumours with a lower radiation dose. (orig.)

A single-aliquot OSL protocol using bracketing regenerative doses to accurately determine equivalent doses in quartz

CERN Document Server

Folz, E

1999-01-01

In most cases, sediments show inherent heterogeneity in their luminescence behaviours and bleaching histories, and identical aliquots are not available: single-aliquot determination of the equivalent dose (ED) is then the approach of choice and the advantages of using regenerative protocols are outlined. Experiments on five laboratory bleached and dosed quartz samples, following the protocol described by Murray and Roberts (1998. Measurement of the equivalent dose in quartz using a regenerative-dose single aliquot protocol. Radiation Measurements 27, 171-184), showed the hazards of using a single regeneration dose: a 10% variation in the regenerative dose yielded some equivalent dose estimates that differed from the expected value by more than 5%. A protocol is proposed that allows the use of different regenerative doses to bracket the estimated equivalent dose. The measured ED is found to be in excellent agreement with the known value when the main regeneration dose is within 10% of the true equivalent dose.

A single-aliquot OSL protocol using bracketing regenerative doses to accurately determine equivalent doses in quartz

International Nuclear Information System (INIS)

Folz, Elise; Mercier, Norbert

1999-01-01

In most cases, sediments show inherent heterogeneity in their luminescence behaviours and bleaching histories, and identical aliquots are not available: single-aliquot determination of the equivalent dose (ED) is then the approach of choice and the advantages of using regenerative protocols are outlined. Experiments on five laboratory bleached and dosed quartz samples, following the protocol described by Murray and Roberts (1998. Measurement of the equivalent dose in quartz using a regenerative-dose single aliquot protocol. Radiation Measurements 27, 171-184), showed the hazards of using a single regeneration dose: a 10% variation in the regenerative dose yielded some equivalent dose estimates that differed from the expected value by more than 5%. A protocol is proposed that allows the use of different regenerative doses to bracket the estimated equivalent dose. The measured ED is found to be in excellent agreement with the known value when the main regeneration dose is within 10% of the true equivalent dose

Single-Dose Lignocaine-Based Blood Cardioplegia in Single Valve Replacement Patients

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Jaydip Ramani

Full Text Available Abstract OBJECTIVE: Myocardial protection is the most important in cardiac surgery. We compared our modified single-dose long-acting lignocaine-based blood cardioplegia with short-acting St Thomas 1 blood cardioplegia in patients undergoing single valve replacement. METHODS: A total of 110 patients who underwent single (aortic or mitral valve replacement surgery were enrolled. Patients were divided in two groups based on the cardioplegia solution used. In group 1 (56 patients, long-acting lignocaine based-blood cardioplegia solution was administered as a single dose while in group 2 (54 patients, standard St Thomas IB (short-acting blood-based cardioplegia solution was administered and repeated every 20 minutes. All the patients were compared for preoperative baseline parameters, intraoperative and all the postoperative parameters. RESULTS: We did not find any statistically significant difference in preoperative baseline parameters. Cardiopulmonary bypass time were 73.8±16.5 and 76.4±16.9 minutes (P=0.43 and cross clamp time were 58.9±10.3 and 66.3±11.2 minutes (P=0.23 in group 1 and group 2, respectively. Mean of maximum inotrope score was 6.3±2.52 and 6.1±2.13 (P=0.65 in group 1 and group 2, respectively. We also did not find any statistically significant difference in creatine-phosphokinase-MB (CPK-MB, Troponin-I levels, lactate level and cardiac functions postoperatively. CONCLUSION: This study proves the safety and efficacy of long-acting lignocaine-based single-dose blood cardioplegia compared to the standard short-acting multi-dose blood cardioplegia in patients requiring the single valve replacement. Further studies need to be undertaken to establish this non-inferiority in situations of complex cardiac procedures especially in compromised patients.

Placental and milk transfer, disposition and elimination of a single oral dose of [14C acetyl] acephate in Sprague Dawley rats

International Nuclear Information System (INIS)

Bakry, N.M.; Salama, A.K.; Abou-Donia, M.B.

1991-01-01

A single oral dose of 40 mg/kg (6.4 μCi/kg) of [ 14 C acetyl]acephate was administered on day 18 of gestation to pregnant Sprague Dawley rats. Eight groups of three rats were killed after 10 min and 0.5, 1, 3, 6, 12, 24, and 48 hr. At the end of the 48 hr experimental period, a total of 22.38% of the dose was exhaled as carbon dioxide, while only 1.25% and 0.60% of the dose were eliminated in the urine and feces, respectively. Trace amount (0.03% of the dose) was recovered in expired air as volatile materials. Radioactive acephate was rapidly absorbed and distributed in the tissues, with levels in most tissues reaching a peak concentration within 1 to 3 hr. The highest concentration of radioactivity was present in the maternal stomach followed by the liver. A total of 0.72% of the dose was recovered in the fetus. In another study, a single oral dose of 40 mg/kg [ 14 C acetyl]acephate was administered to the dams right after delivery. Nursing and suckling groups were killed at intervals of 1, 3, 6, 12, 24, 36, and 48 hr after dosing. Generally, the highest concentrations of radioactivity were present in the stomach, small intestine, liver, lung, and kidneys. A total of 0.96% of the dose was recovered in the sucklings

Minimal infectious doses and prepatent periods in Giardia muris, Spironucleus muris and Tritrichomonas muris.

Science.gov (United States)

Stachan, R; Kunstýr, I

1983-12-01

The minimal infectious doses (MID) of Giardia muris cysts, Spironucleus muris cysts and Tritrichomonas muris pseudocysts for athymic mice were determined. A novel micromanipulator-aided technique was developed for selecting small exact numbers of specified fresh or old cysts/pseudocysts from a faecal homogenate. This technique can also be of value in manipulating protozoan parasites of any particular species. Only fresh cysts/pseudocysts, which appeared bright under phase contrast optics, were infectious. Older cysts and pseudocysts which appeared dark in phase contrast were not infectious. The MID for three murine intestinal flagellates addressed above were: 10 (between 5 and 20), 1 and 5 cysts/pseudocysts respectively. Corresponding prepatent periods (PP) were 8, 5 and 10 days. A relation was evident between the infectious dose and the PP: The prepatent period shortened with an increased infectious dose.

Quantitative Single-letter Sequencing: a method for simultaneously monitoring numerous known allelic variants in single DNA samples

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Duborjal Hervé

2008-02-01

Full Text Available Abstract Background Pathogens such as fungi, bacteria and especially viruses, are highly variable even within an individual host, intensifying the difficulty of distinguishing and accurately quantifying numerous allelic variants co-existing in a single nucleic acid sample. The majority of currently available techniques are based on real-time PCR or primer extension and often require multiplexing adjustments that impose a practical limitation of the number of alleles that can be monitored simultaneously at a single locus. Results Here, we describe a novel method that allows the simultaneous quantification of numerous allelic variants in a single reaction tube and without multiplexing. Quantitative Single-letter Sequencing (QSS begins with a single PCR amplification step using a pair of primers flanking the polymorphic region of interest. Next, PCR products are submitted to single-letter sequencing with a fluorescently-labelled primer located upstream of the polymorphic region. The resulting monochromatic electropherogram shows numerous specific diagnostic peaks, attributable to specific variants, signifying their presence/absence in the DNA sample. Moreover, peak fluorescence can be quantified and used to estimate the frequency of the corresponding variant in the DNA population. Using engineered allelic markers in the genome of Cauliflower mosaic virus, we reliably monitored six different viral genotypes in DNA extracted from infected plants. Evaluation of the intrinsic variance of this method, as applied to both artificial plasmid DNA mixes and viral genome populations, demonstrates that QSS is a robust and reliable method of detection and quantification for variants with a relative frequency of between 0.05 and 1. Conclusion This simple method is easily transferable to many other biological systems and questions, including those involving high throughput analysis, and can be performed in any laboratory since it does not require specialized

Optical orthogonal code-division multiple-access system - Part 2: Multibits/sequence-period OOCDMA

Science.gov (United States)

Kwon, Hyuck M.

1994-08-01

In a recently proposed optical orthogonal code division multiple-access (OOCDMA) system, one bit of user's data is transmitted per sequence-period, and a threshold is employed for the final bit decision. In this paper, a system that can transmit multibits per sequence-period is introduced, and avalanche photodiode (APD) noise, thermal noise, and interference, are included. This system, derived by exploiting orthogonal properties of the OOCDMA code sequence and using a maximum search (instead of a threshold) in the final decision, is log(sub 2) F times higher in throughput, where F is sequence-period. For example, four orders of magnitude are better in bit error probability at - 56 dBW received laser power, with F = 1000 chips, 10 'marks' in a sequence, and 10 users of 30 Mb/s data rate for one-bit/sequence-period and 270 Mb/s data rate for multibits/sequence-period system. Furthermore, an exact analysis is performed for the log(sub 2)F bits/sequence-period system with a hard-limiter placed before the receiver, and its performance is compared to the performance without hard-limiter, for the chip-synchronous case. The improvement from using a hard-limiter is significant in the log(sub 2)F bits/sequence-period OCCDMA system.

Organ dose from inhaled radionuclides taking lull period into account

International Nuclear Information System (INIS)

Datta, S.

1982-01-01

The dosimetry of inhaled radionuclides is generally carried out in accordance with the lung model recommended by the ICRP Task Group on Lung Dynamics. The relevant expressions are integrated over a given period, assuming continuous inhalation in an atmosphere of constant aerosol concentration. Though for the same amount of intake the dose commitment is found to be independent of variations in the rate of intake, the dose determined over specific intervals of time, is influenced by it or by lull intervals therein. Formulae are developed to arrive at doses to different organs when the subject's intake is constant and continuous for 8 hours, followed by a lull period of 16 hours each day. Results are given for a number of radionuclides and are compared with values characteristic of continuous inhalation. It is observed that when exposure is assumed to be continuous the dose for the same intake of activity is underestimated as compared to the dose when lull period is taken into account. For working periods of 6 days and 30 days the underestimate ranges from 5%-20% and 0.6% to 4.5% respectively. (author)

Determination of burial dose in incompletely bleached fluvial samples using single grains of quartz

DEFF Research Database (Denmark)

Thomsen, Kristina Jørkov; Murray, A.S.; Bøtter-Jensen, Lars

2007-01-01

We determine the burial dose in three known-age incompletely bleached fluvial samples using single grains of quartz. Estimation of burial dose in incompletely bleached samples requires that the characteristics of the well-bleached part of the distribution are known in order to distinguish between...... well-bleached and poorly bleached grains. It is especially important to investigate if the uncertainties assigned to individual estimates of dose adequately describe the observed variability in well-bleached dose distributions. We investigate this by quantifying the overdispersion in laboratory-bleached...

Effects of split-dose irradiation of the rabbit's eye - a histopathological study

International Nuclear Information System (INIS)

Grabenbauer, G.G.

1987-01-01

Thirty-six rabbits were included in a study investigating into the effects of split-dose 300 KV X-irradiation on the cornea, ciliary body, nictitating membrane and lacrimal gland. In each animal, soly the right the eye was irradiated using total doses of 21 Gy, 30 Gy, 36 Gy and 45 Gy that were administered according to a fixed schedule in fractions of 3 Gy five times per week. After latency periods of six weeks, three months and six months the animals receiving 21 Gy, 30 Gy and 36 Gy showed no changes of the bulbi, eye lids and lacrimal glands that could be ascertained by histopathological evaluation. In the animals exposed to the 45 Gy dose, changes of the cornea and conjunctiva caused by radiation injuries to the lacrimal glands and conjunctival goblet cells started to appear after a minimum period of 3 months. This dose level was also the threshold for the occurrence of corneal damage or even ulceration as a result of secondary reduction or qualitative change of lacrimal secretions. (ECB) [de

Sequence periodicity in nucleosomal DNA and intrinsic curvature.

Science.gov (United States)

Nair, T Murlidharan

2010-05-17

Most eukaryotic DNA contained in the nucleus is packaged by wrapping DNA around histone octamers. Histones are ubiquitous and bind most regions of chromosomal DNA. In order to achieve smooth wrapping of the DNA around the histone octamer, the DNA duplex should be able to deform and should possess intrinsic curvature. The deformability of DNA is a result of the non-parallelness of base pair stacks. The stacking interaction between base pairs is sequence dependent. The higher the stacking energy the more rigid the DNA helix, thus it is natural to expect that sequences that are involved in wrapping around the histone octamer should be unstacked and possess intrinsic curvature. Intrinsic curvature has been shown to be dictated by the periodic recurrence of certain dinucleotides. Several genome-wide studies directed towards mapping of nucleosome positions have revealed periodicity associated with certain stretches of sequences. In the current study, these sequences have been analyzed with a view to understand their sequence-dependent structures. Higher order DNA structures and the distribution of molecular bend loci associated with 146 base nucleosome core DNA sequence from C. elegans and chicken have been analyzed using the theoretical model for DNA curvature. The curvature dispersion calculated by cyclically permuting the sequences revealed that the molecular bend loci were delocalized throughout the nucleosome core region and had varying degrees of intrinsic curvature. The higher order structures associated with nucleosomes of C.elegans and chicken calculated from the sequences revealed heterogeneity with respect to the deviation of the DNA axis. The results points to the possibility of context dependent curvature of varying degrees to be associated with nucleosomal DNA.

A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis.

Science.gov (United States)

Yasuda, Mitsuru; Ito, Shin; Kido, Akira; Hamano, Kiminari; Uchijima, Yutaka; Uwatoko, Noriyasu; Kusuyama, Hiroyuki; Watanabe, Akiko; Miyamura, Ryuzou; Miyata, Kazutoyo; Deguchi, Takashi

2014-11-01

We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability. We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients. We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild. The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The effects of peritoneal dialysis on the single dose and steady state pharmacokinetics of valproic acid in a uremic epileptic child.

Science.gov (United States)

Orr, J M; Farrell, K; Abbott, F S; Ferguson, S; Godolphin, W J

1983-01-01

The pharmacokinetics of valproic acid (VPA) have been studied during peritoneal dialysis in a uremic male epileptic child following a single 500 mg dose and after multiple doses over 5 months (700 mg daily) of valproic acid as the syrup. Serum level decline was biphasic in both instances with a terminal half-life of 27.2 after the single dose and 10.2 h at steady-state. Total serum clearance was 0.0236 l/h/kg after the single dose and increased to 0.0408 l/h/kg after 5 months. Free (intrinsic) serum clearances were 0.1489 and 0.1518 l/h/kg and serum free fractions were 0.224 and 0.272 respectively for the single dose and steady-state studies. Peritoneal dialysis for periods of 12 or 24 h removed an average of 4.5% of the VPA dose.

Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

Science.gov (United States)

Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

2018-01-20

The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

Pervasive within-Mitochondrion Single-Nucleotide Variant Heteroplasmy as Revealed by Single-Mitochondrion Sequencing

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Jacqueline Morris

2017-12-01

Full Text Available Summary: A number of mitochondrial diseases arise from single-nucleotide variant (SNV accumulation in multiple mitochondria. Here, we present a method for identification of variants present at the single-mitochondrion level in individual mouse and human neuronal cells, allowing for extremely high-resolution study of mitochondrial mutation dynamics. We identified extensive heteroplasmy between individual mitochondrion, along with three high-confidence variants in mouse and one in human that were present in multiple mitochondria across cells. The pattern of variation revealed by single-mitochondrion data shows surprisingly pervasive levels of heteroplasmy in inbred mice. Distribution of SNV loci suggests inheritance of variants across generations, resulting in Poisson jackpot lines with large SNV load. Comparison of human and mouse variants suggests that the two species might employ distinct modes of somatic segregation. Single-mitochondrion resolution revealed mitochondria mutational dynamics that we hypothesize to affect risk probabilities for mutations reaching disease thresholds. : Morris et al. use independent sequencing of multiple individual mitochondria from mouse and human brain cells to show high pervasiveness of mutations. The mutations are heteroplasmic within single mitochondria and within and between cells. These findings suggest mechanisms by which mutations accumulate over time, resulting in mitochondrial dysfunction and disease. Keywords: single mitochondrion, single cell, human neuron, mouse neuron, single-nucleotide variation

Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing.

Science.gov (United States)

Zheng, Chunhong; Zheng, Liangtao; Yoo, Jae-Kwang; Guo, Huahu; Zhang, Yuanyuan; Guo, Xinyi; Kang, Boxi; Hu, Ruozhen; Huang, Julie Y; Zhang, Qiming; Liu, Zhouzerui; Dong, Minghui; Hu, Xueda; Ouyang, Wenjun; Peng, Jirun; Zhang, Zemin

2017-06-15

Systematic interrogation of tumor-infiltrating lymphocytes is key to the development of immunotherapies and the prediction of their clinical responses in cancers. Here, we perform deep single-cell RNA sequencing on 5,063 single T cells isolated from peripheral blood, tumor, and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences, enable us to identify 11 T cell subsets based on their molecular and functional properties and delineate their developmental trajectory. Specific subsets such as exhausted CD8 + T cells and Tregs are preferentially enriched and potentially clonally expanded in hepatocellular carcinoma (HCC), and we identified signature genes for each subset. One of the genes, layilin, is upregulated on activated CD8 + T cells and Tregs and represses the CD8 + T cell functions in vitro. This compendium of transcriptome data provides valuable insights and a rich resource for understanding the immune landscape in cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

Single-Cell RNA Sequencing of Glioblastoma Cells.

Science.gov (United States)

Sen, Rajeev; Dolgalev, Igor; Bayin, N Sumru; Heguy, Adriana; Tsirigos, Aris; Placantonakis, Dimitris G

2018-01-01

Single-cell RNA sequencing (sc-RNASeq) is a recently developed technique used to evaluate the transcriptome of individual cells. As opposed to conventional RNASeq in which entire populations are sequenced in bulk, sc-RNASeq can be beneficial when trying to better understand gene expression patterns in markedly heterogeneous populations of cells or when trying to identify transcriptional signatures of rare cells that may be underrepresented when using conventional bulk RNASeq. In this method, we describe the generation and analysis of cDNA libraries from single patient-derived glioblastoma cells using the C1 Fluidigm system. The protocol details the use of the C1 integrated fluidics circuit (IFC) for capturing, imaging and lysing cells; performing reverse transcription; and generating cDNA libraries that are ready for sequencing and analysis.

Realizing all reduced syzygy sequences in the planar three-body problem

International Nuclear Information System (INIS)

Moeckel, Richard; Montgomery, Richard

2015-01-01

The configuration space of the planar three-body problem, reduced by rotations and with collisions excluded, has a rich topology which supports a large set of free homotopy classes. These classes have a simple description in terms of syzygy (or eclipse) sequences. Each homotopy class corresponds to a unique ‘reduced’ syzygy sequence. We prove that each reduced syzygy sequence is realized by a periodic solution of the rotation-reduced Newtonian planar three-body problem. The realizing solutions have small, nonzero angular momentum, repeatedly come very close to triple collision, and have lots of ‘stutters’—repeated syzygies of the same type, which cancel out up to homotopy. The heart of the proof stems from the work by one of us on symbolic dynamics arising out of the central configurations after the triple collision is blown up using McGehee's method. We end with a list of open problems. (paper)

Effect of a Single Dose of Dextromethorphan on Psychomotor Performance and Working Memory Capacity

OpenAIRE

Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.; Ashor, Ammar Waham

2012-01-01

Background: Previous studies show that the prolonged use of dextromethorphan produces cognitive deterioration in humans. Aim: The aim of this study was to investigate the effect of a single dose of dextroemthrophan on psychomotor performance and working memory capacity. Materials and Methods: This is a randomized, double-blind, controlled, and prospective study. Thirty-six (17 women, 19 men) medical students enrolled in the study; half of them (7 women, 11 men) were given placebo, while the o...

Adrenaline (epinephrine) dosing period and survival after in-hospital cardiac arrest: a retrospective review of prospectively collected data.

Science.gov (United States)

Warren, Sam A; Huszti, Ella; Bradley, Steven M; Chan, Paul S; Bryson, Chris L; Fitzpatrick, Annette L; Nichol, Graham

2014-03-01

Expert guidelines for treatment of cardiac arrest recommend administration of adrenaline (epinephrine) every three to five minutes. However, the effects of different dosing periods of epinephrine remain unclear. We sought to evaluate the association between epinephrine average dosing period and survival to hospital discharge in adults with an in-hospital cardiac arrest (IHCA). We performed a retrospective review of prospectively collected data on 20,909 IHCA events from 505 hospitals participating in the Get With The Guidelines-Resuscitation (GWTG-R) quality improvement registry. Epinephrine average dosing period was defined as the time between the first epinephrine dose and the resuscitation endpoint, divided by the total number of epinephrine doses received subsequent to the first epinephrine dose. Associations with survival to hospital discharge were assessed by using generalized estimating equations to construct multivariable logistic regression models. Compared to a referent epinephrine average dosing period of 4 to <5 min per dose, survival to hospital discharge was significantly higher in patients with the following epinephrine average dosing periods: for 6 to <7 min/dose, adjusted odds ratio [OR], 1.41 (95%CI: 1.12, 1.78); for 7 to <8 min/dose, adjusted OR, 1.30 (95%CI: 1.02, 1.65); for 8 to <9 min/dose, adjusted OR, 1.79 (95%CI: 1.38, 2.32); for 9 to <10 min/dose, adjusted OR, 2.17 (95%CI: 1.62, 2.92). This pattern was consistent for both shockable and non-shockable cardiac arrest rhythms. Less frequent average epinephrine dosing than recommended by consensus guidelines was associated with improved survival of in-hospital cardiac arrest. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effect of a single dose of dextromethorphan on psychomotor performance and working memory capacity.

Science.gov (United States)

Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Ashor, Ammar Waham

2012-04-01

Previous studies show that the prolonged use of dextromethorphan produces cognitive deterioration in humans. The aim of this study was to investigate the effect of a single dose of dextroemthrophan on psychomotor performance and working memory capacity. This is a randomized, double-blind, controlled, and prospective study. Thirty-six (17 women, 19 men) medical students enrolled in the study; half of them (7 women, 11 men) were given placebo, while the other half (10 women, 8 men) received dextromethorphan. The choice reaction time, critical flicker fusion threshold, and N-back working memory task were measured before and after 2 h of taking the drugs. Dextromethorphan showed a significant deterioration in the 3-back working memory task (P0.05). On the other hand, placebo showed no significant changes as regards the choice reaction time, critical flicker fusion threshold, and N-back working memory task (P>0.05). A single dose of dextromethorphan has no effect on attention and arousal but may significantly impair the working memory capacity.

High-throughput sequencing reveals microbial communities in drinking water treatment sludge from six geographically distributed plants, including potentially toxic cyanobacteria and pathogens.

Science.gov (United States)

Xu, Hangzhou; Pei, Haiyan; Jin, Yan; Ma, Chunxia; Wang, Yuting; Sun, Jiongming; Li, Hongmin

2018-04-10

The microbial community structures of drinking water treatment sludge (DWTS) generated for raw water (RW) from different locations and with different source types - including river water, lake water and reservoir water -were investigated using high-throughput sequencing. Because the unit operations in the six DWTPs were similar, community composition in fresh sludge may be determined by microbial community in the corresponding RW. Although Proteobacteria, Cyanobacteria, Bacteroidetes, Firmicutes, Verrucomicrobia, and Planctomycetes were the dominant phyla among the six DWTS samples, no single phylum exhibited similar abundance across all the samples, owing to differences in total phosphorus, chemical oxygen demand, Al, Fe, and chloride in RW. Three genera of potentially toxic cyanobacteria (Planktothrix, Microcystis and Cylindrospermopsis), and four potential pathogens (Escherichia coli, Bacteroides ovatus, Prevotella copri and Rickettsia) were found in sludge samples. Because proliferation of potentially toxic cyanobacteria and Rickettsia in RW was mainly affected by nutrients, while growth of Escherichia coli, Bacteroides ovatus and Prevotella copri in RW may be influenced by Fe, control of nutrients and Fe in RW is essential to decrease toxic cyanobacteria and pathogens in DWTS. Copyright © 2018 Elsevier B.V. All rights reserved.

The dose dependency of the over-dispersion of quartz OSL single grain dose distributions

DEFF Research Database (Denmark)

Thomsen, Kristina Jørkov; Murray, Andrew S.; Jain, Mayank

2012-01-01

The use of single grain quartz OSL dating has become widespread over the past decade, particularly with application to samples likely to have been incompletely bleached before burial. By reducing the aliquot size to a single grain the probability of identifying the grain population most likely...... to have been well-bleached at deposition is maximised and thus the accuracy with which the equivalent dose can be determined is – at least in principle – improved. However, analysis of single grain dose distributions requires knowledge of the dispersion of the well-bleached part of the dose distribution....... This can be estimated by measurement of a suitable analogue, e.g. a well-bleached aeolian sample, but this requires such an analogue to be available, and in addition the assumptions that the sample is in fact a) well-bleached, and b) has a similar dose rate heterogeneity to the fossil deposit. Finally...

Single dose planning for radioiodine-131 therapy of Graves' disease

International Nuclear Information System (INIS)

Kita, Tamotsu; Yokoyama, Kunihiko; Kinuya, Seigo; Taki, Junichi; Michigishi, Takatoshi; Tonami, Norihisa

2004-01-01

Patients with Graves' disease were studied one year after radioiodine-131 therapy to assess the relationship between the effectiveness of the therapy and the radioiodine doses used. Patients were classified into three groups according to thyroid function as hyperthyroidism, euthyroidism and hypothyroidism at one year after I-131 therapy. In these groups we compared the mean values of dose, dose per thyroid weight calculated with I-123 uptake before the therapy (pre D/W), dose per thyroid weight calculated with therapeutic I-131 uptake (post D/W), and absorbed dose. No significant differences were found between the three groups in terms of dose or pre D/W. The mean values of post D/W and absorbed dose in the non-hyperthyroid (euthyroid and hypothyroid) group were significantly greater than those in the hyperthyroid group. Post D/W of 6.3 MBq/g was a threshold separating the non-hyperthyroid group from the hyperthyroid group. There was no correlation between pre D/W and post D/W; however, the mean post D/W was significantly greater than the mean pre D/W. All patients with pre D/W above 6.3 MBq/g showed non-hyperthyroidism at one year after the radioiodine treatment. No indicators before the radioiodine therapy had significant relationships with the effectiveness of the therapy at one year after the treatment. However, the single therapy planned for setting the pre D/W above 6.3 MBq/g will certainly make the patients non-hyperthyroid. As this proposal of dose planning is based on a small number of patients, further study is needed. (author)

Distribution, variability, and predictors of urinary bisphenol A levels in 50 North Carolina adults over a six-week monitoring period.

Science.gov (United States)

Morgan, Marsha K; Nash, Maliha; Barr, Dana Boyd; Starr, James M; Scott Clifton, M; Sobus, Jon R

2018-03-01

Bisphenol A (BPA) is commonly manufactured to make polycarbonate plastics and epoxy resins for use in consumer products and packaged goods. BPA has been found in several different types of environmental media (e.g., food, dust, and air). Many cross-sectional studies have frequently detected BPA concentrations in adult urine samples. However, limited data are available on the temporal variability and important predictors of urinary BPA concentrations in adults. In this work, the major objectives were to: 1) quantify BPA levels in duplicate-diet solid food, drinking water, hard floor surface wipe, and urine samples (first-morning void [FMV], bedtime, and 24-h) collected from adults over a six-week monitoring period; 2) determine the temporal variability of urinary BPA levels using concentration, specific gravity (SG) adjusted, creatinine (CR) adjusted, and excretion rate values, and; 3) examine associations between available study factors and urinary BPA concentrations. In 2009-2011, a convenience sample of 50 adults was recruited from residential settings in North Carolina. The participants completed diaries and collected samples during weeks 1, 2, and/or 6 of a six-week monitoring period. BPA was detected in 38%, 4%, and 99% of the solid food (n=775), drinking water (n=50), and surface wipe samples (n=138), respectively. Total BPA (free plus conjugated) was detected in 98% of the 2477 urine samples. Median urinary BPA levels were 2.07ng/mL, 2.20ng/mL-SG, 2.29ng/mg, and 2.31ng/min for concentration, SG-adjusted, CR-adjusted, and excretion rate values, respectively. The intraclass correlation coefficient (ICC) estimates for BPA showed poor reproducibility (≤0.35) for all urine sample types and methods over a day, week, and six weeks. CR-adjusted bedtime voids collected over six-weeks required the fewest, realistic number of samples (n=11) to obtain a reliable biomarker estimate (ICC=0.80). Results of linear mixed-effects models showed that sex, race, season, and CR

Determination of vitality in myocardial infarction. Comparison of single- and multi-slice MRI techniques with TurboFlash and TrueFISP sequences

International Nuclear Information System (INIS)

Huber, A.; Schoenberg, S.O.; Spannagl, B.; Rieber, J.; Klauss, V.; Reiser, M.F.

2004-01-01

The aim of the study was to compare the diagnostic accuracy in imaging viability of the myocardium with a multislice inversions recovery 2D single shot TrueFISP sequence and an established inversion recovery TurboFlash sequence. Twelve patients with myocardial infarction were examined at a 1.5 tesla MR system (Sonata, Siemens, Medical Systems) 10 min after application of a single dose multihance (0,1 mmol/kg body weight) with a 2D multislice technique (inversion recovery single shot TrueFISP), that allows to image the entire short axis during one breathhold and a 2D single slice technique (inversion recovery TurboFlash), that requires one breathhold per slice. Signal intensity was determined in normal myocardium, in the infarcted myocardium and in the left ventricle. The contrast/noise ratio of normal and infarcted myocardium was determined. The areas of hyperintense infarction were compared for both sequence techniques. The multislice single shot 2D IR-TrueFisp sequence has a lower contrast/noise ratio than the IR-TurboFlash sequence (mean values 6.9 vs. 12.5) for viable and non viable myocardium. The assessment of the volume of the infarction is possible with excellent correlation of both techniques (r=0.97, p [de

A Cohort Study of Preoperative Single Dose Versus Four Doses of Antibiotics for Patients With Non-Complicated Acute Appendicitis

Directory of Open Access Journals (Sweden)

Salah H. Al Janaby

2017-02-01

Full Text Available Objective: To Test the efficacy of single preoperative dose of Cefotaxime 1gm and Metronidazole 500mg in reducing the surgical site infections (SSIs after open appendectomy in patients with non-complicated appendicitis (NCA Place and Duration of Study: Al Hilla General Teaching Hospital, Babel Governorate-Iraq, from January 2013 to January 2014. Patients & Methods: 100 patients, who underwent appendectomy for NCA and fulfilled the selection criteria, were randomized into two groups. The patients in group A received a single dose of pre-operative antibiotics (Cefotaxime sodium and metronidazole, while the group B patients received three more dose of the same antibiotics postoperatively. Patients of both groups were followed-up for 30 days to assess the postoperative infective complications. Results: Group A had 48, while group B comprised of 52 patients. The groups were comparable in the baseline characteristics. Statistically, P value in rates of SSIs between both the groups was 0.9182. None of the patients developed intra-abdominal collection. Conclusion: Single dose of pre-operative antibiotics (Cefotaxime and metronidazole was sufficient in reducing the SSIs after appendectomy for NPA. Postoperative antibiotics did not add an appreciable clinical benefit in these patients. Key words: Preoperative antibiotics, Appendectomy, Surgical site infection, Non-complicated appendicitis Abbreviations: SSI: Surgical Site Infection, NCA: non-complicated appendicitis CDC Center of Disease Control.

International interlaboratory study comparing single organism 16S rRNA gene sequencing data: Beyond consensus sequence comparisons

Science.gov (United States)

Olson, Nathan D.; Lund, Steven P.; Zook, Justin M.; Rojas-Cornejo, Fabiola; Beck, Brian; Foy, Carole; Huggett, Jim; Whale, Alexandra S.; Sui, Zhiwei; Baoutina, Anna; Dobeson, Michael; Partis, Lina; Morrow, Jayne B.

2015-01-01

This study presents the results from an interlaboratory sequencing study for which we developed a novel high-resolution method for comparing data from different sequencing platforms for a multi-copy, paralogous gene. The combination of PCR amplification and 16S ribosomal RNA gene (16S rRNA) sequencing has revolutionized bacteriology by enabling rapid identification, frequently without the need for culture. To assess variability between laboratories in sequencing 16S rRNA, six laboratories sequenced the gene encoding the 16S rRNA from Escherichia coli O157:H7 strain EDL933 and Listeria monocytogenes serovar 4b strain NCTC11994. Participants performed sequencing methods and protocols available in their laboratories: Sanger sequencing, Roche 454 pyrosequencing®, or Ion Torrent PGM®. The sequencing data were evaluated on three levels: (1) identity of biologically conserved position, (2) ratio of 16S rRNA gene copies featuring identified variants, and (3) the collection of variant combinations in a set of 16S rRNA gene copies. The same set of biologically conserved positions was identified for each sequencing method. Analytical methods using Bayesian and maximum likelihood statistics were developed to estimate variant copy ratios, which describe the ratio of nucleotides at each identified biologically variable position, as well as the likely set of variant combinations present in 16S rRNA gene copies. Our results indicate that estimated variant copy ratios at biologically variable positions were only reproducible for high throughput sequencing methods. Furthermore, the likely variant combination set was only reproducible with increased sequencing depth and longer read lengths. We also demonstrate novel methods for evaluating variable positions when comparing multi-copy gene sequence data from multiple laboratories generated using multiple sequencing technologies. PMID:27077030

International interlaboratory study comparing single organism 16S rRNA gene sequencing data: Beyond consensus sequence comparisons

Directory of Open Access Journals (Sweden)

Nathan D. Olson

2015-03-01

Full Text Available This study presents the results from an interlaboratory sequencing study for which we developed a novel high-resolution method for comparing data from different sequencing platforms for a multi-copy, paralogous gene. The combination of PCR amplification and 16S ribosomal RNA gene (16S rRNA sequencing has revolutionized bacteriology by enabling rapid identification, frequently without the need for culture. To assess variability between laboratories in sequencing 16S rRNA, six laboratories sequenced the gene encoding the 16S rRNA from Escherichia coli O157:H7 strain EDL933 and Listeria monocytogenes serovar 4b strain NCTC11994. Participants performed sequencing methods and protocols available in their laboratories: Sanger sequencing, Roche 454 pyrosequencing®, or Ion Torrent PGM®. The sequencing data were evaluated on three levels: (1 identity of biologically conserved position, (2 ratio of 16S rRNA gene copies featuring identified variants, and (3 the collection of variant combinations in a set of 16S rRNA gene copies. The same set of biologically conserved positions was identified for each sequencing method. Analytical methods using Bayesian and maximum likelihood statistics were developed to estimate variant copy ratios, which describe the ratio of nucleotides at each identified biologically variable position, as well as the likely set of variant combinations present in 16S rRNA gene copies. Our results indicate that estimated variant copy ratios at biologically variable positions were only reproducible for high throughput sequencing methods. Furthermore, the likely variant combination set was only reproducible with increased sequencing depth and longer read lengths. We also demonstrate novel methods for evaluating variable positions when comparing multi-copy gene sequence data from multiple laboratories generated using multiple sequencing technologies.

Pharmacokinetics and Safety of DW1029M, a Botanical Drug for the Treatment of Diabetic Nephropathy, Following Single Doses in Healthy Subjects.

Science.gov (United States)

Kim, Yunjeong; Jeon, Ji-Young; Kim, Eun-Young; Lim, Cheol-Hee; Jang, Hwan Bong; Kim, Min-Gul

2017-09-01

DW1029M is a botanical extract of Morus albalinne root bark and Puerariae radix that is used for the treatment of diabetic nephropathy. This study evaluated the safety and pharmacokinetics of DW1029M following its administration in healthy Korean subjects. We conducted a randomized, open-label, single-dose, crossover phase 1 clinical study. During each period, subjects received 300, 600, or 1200 mg oral doses of DW1029M. Plasma concentrations of puerarin, daidzin, and daidzein were analyzed using a liquid chromatography-tandem mass spectrometry. Six healthy male subjects completed the study. The maximum concentration of the drug in the plasma (C max ) and area under the plasma drug concentration-time curve to the last measurable concentration (AUC last ) for puerarin, daidzin, and daidzein were assessed after oral administration of DW1029M. No serious adverse events or clinically or statistically significant adverse events associated with any of the drug levels were observed. The results of the measurement of vital signs, electrocardiogram, laboratory tests, and physical examinations indicated that no clinically significant changes occurred during this study. The DW1029M tablet was safe and well tolerated over a single dose range of 300-1200 mg. This pharmacokinetic study of a botanical drug may aid in the development of DW1029M. © 2017, The American College of Clinical Pharmacology.

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

Science.gov (United States)

Thyssen, An; Solanki, Bhavna; Treem, William

2012-07-01

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

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

Science.gov (United States)

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

2011-12-01

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

Pharmacokinetics of [14C]teicoplanin in male rats after single intravenous dose

International Nuclear Information System (INIS)

Bernareggi, A.; Cavenaghi, L.; Assandri, A.

1986-01-01

The pharmacokinetic profile of [ 14 C]teicoplanin was studied in male Sprague-Dawley rats given a single 10,000-U/kg intravenous dose. The disposition of the antimicrobial activity in the body was estimated by a three-compartment open model. Plasma concentration data were fitted to a three-exponent equation. The profile of total 14 C in plasma was similar to that of the microbiological activity. The cumulative recovery of total 14 C 5 days after drug administration averaged 76.3% of the administered dose in the urine and 8.7% in the feces. The residual dose remaining in the animal carcasses was 11.1%. Teicoplanin was widely distributed in the body. In almost all organs, the maximum concentration of [ 14 C]teicoplanin was already reached at the first time of killing, which was 0.25 h after the administration of drug. The liver, kidneys, skin, and fat contained most of the residual dose found in the animal carcasses 120 h after administration and behaved as a deep compartment with the adrenal glands and spleen

single dose pharmacokinetics of mefloquine in healthy nigerian

African Journals Online (AJOL)

BSN

Mefloquine 500mg single dose was administered and blood samples were collected ... particle size ODS Hypersil (HETP, Macclesfield, UK) at a pressure of 55 Mpa .... dose to area under the plasma drug concentration - time curve, assuming ...

Sequencing of individual chromosomes of plant pathogenic Fusarium oxysporum.

Science.gov (United States)

Kashiwa, Takeshi; Kozaki, Toshinori; Ishii, Kazuo; Turgeon, B Gillian; Teraoka, Tohru; Komatsu, Ken; Arie, Tsutomu

2017-01-01

A small chromosome in reference isolate 4287 of F. oxysporum f. sp. lycopersici (Fol) has been designated as a 'pathogenicity chromosome' because it carries several pathogenicity related genes such as the Secreted In Xylem (SIX) genes. Sequence assembly of small chromosomes in other isolates, based on a reference genome template, is difficult because of karyotype variation among isolates and a high number of sequences associated with transposable elements. These factors often result in misassembly of sequences, making it unclear whether other isolates possess the same pathogenicity chromosome harboring SIX genes as in the reference isolate. To overcome this difficulty, single chromosome sequencing after Contour-clamped Homogeneous Electric Field (CHEF) separation of chromosomes was performed, followed by de novo assembly of sequences. The assembled sequences of individual chromosomes were consistent with results of probing gels of CHEF separated chromosomes with SIX genes. Individual chromosome sequencing revealed that several SIX genes are located on a single small chromosome in two pathogenic forms of F. oxysporum, beyond the reference isolate 4287, and in the cabbage yellows fungus F. oxysporum f. sp. conglutinans. The particular combination of SIX genes on each small chromosome varied. Moreover, not all SIX genes were found on small chromosomes; depending on the isolate, some were on big chromosomes. This suggests that recombination of chromosomes and/or translocation of SIX genes may occur frequently. Our method improves sequence comparison of small chromosomes among isolates. Copyright © 2016 Elsevier Inc. All rights reserved.

A preliminary study on doses of 60Co-γ ray for mutation breeding of Roegneria

International Nuclear Information System (INIS)

Jiang Yun; Lin Yang; Xuan Pu; Luo Xiaomei; Zhang Haiqin

2011-01-01

Six groups from three species of Roegneria were radiated with eight ladders of 60 Co-γ ray for finding the most suitable absorbed dose. The dose ladders were CK (0 Gy), 50 Gy, 100 Gy, 150 Gy, 200 Gy, 250 Gy, 300 Gy and 400 Gy. The half-lethal dose of six gourps, generated by multi-Target Single Hit Model Equation, were from 59.6 Gy to 172.8 Gy. Germination percentage of seeds, height of seeding, plant survival percentage and setting percentage were investigated. The most suitable absorbed doses of each species primerly were deduced from these data. The research provide a valuable reference for Roegneria mutation breeding on chousing the absorbed does. (authors)

Urease activity as a risk factor for caries development in children during a three-year study period: a survival analysis approach

Science.gov (United States)

Morou-Bermudez, E; Elias-Boneta, A; Billings, RJ; Burne, RA; Garcia-Rivas, V; Brignoni-Nazario, V; Suárez-Pérez, E

2011-01-01

Recent cross-sectional studies suggest that reduced ability to generate alkali via the urease pathway in dental plaque may be an important caries risk factor, but it has not been assessed prospectively. OBJECTIVE To evaluate the effect of plaque and saliva urease activity on the risk for developing new caries over a three-year period in children. METHODS A panel of 80 children, three to six years of age at recruitment, was followed prospectively for three years. Plaque urease activity, saliva urease activity and dental caries were measured every six months. Survival analysis methodology was used to evaluate the effect of urease on caries development during the study period adjusted for gender, age, baseline caries levels, sugar consumption, amount of plaque, and mutans streptococci levels. RESULTS The risk for developing new caries increased in a dose-responsive manner with increasing levels of urease activity in saliva (adjusted HRQ4 vs. Q1: 4.98; 95%CI: 1.33, 18.69) and with decreasing urease activity in plaque (adjusted HRQ4 vs. Q1: 0.29; 95%CI: 0.11, 0.76). Multiple measurements of urease activity were conducted to overcome the variability of urease activity in this study. Baseline caries and mutans streptococci in saliva were also important predictors of caries risk. CONCLUSIONS Increased urease activity in saliva can be an indicator of increased caries risk in children, while increased urease activity in plaque may be associated with reduced caries risk. The reproducibility of urease measurements must be improved before these findings can be further tested and clinically applied. PMID:21784411

Three-dimensional dose accumulation in pseudo-split-field IMRT and brachytherapy for locally advanced cervical cancer

DEFF Research Database (Denmark)

Sun, Baozhou; Yang, Deshan; Esthappan, Jackie

2015-01-01

-field intensity-modulated radiation therapy (IMRT) and image-guided BT in locally advanced cervical cancer. METHODS AND MATERIALS: Thirty-three patients treated with split-field-IMRT to 45.0-51.2 Gy in 1.6-1.8 Gy per fraction to the elective pelvic lymph nodes and to 20 Gy to the central pelvis region were...... included in this study. Patients received six weekly fractions of high-dose rate BT to 6.5-7.3 Gy per fraction. A dose tracker software was developed to compute the equivalent dose in 2-Gy fractions (EQD2) to gross tumor volume (GTV), organs-at-risk and point A. Total dose-volume histogram parameters were...

The dose dependency of the over-dispersion of quartz OSL single grain dose distributions

International Nuclear Information System (INIS)

Thomsen, Kristina J.; Murray, Andrew; Jain, Mayank

2012-01-01

The use of single grain quartz OSL dating has become widespread over the past decade, particularly with application to samples likely to have been incompletely bleached before burial. By reducing the aliquot size to a single grain the probability of identifying the grain population most likely to have been well-bleached at deposition is maximised and thus the accuracy with which the equivalent dose can be determined is – at least in principle – improved. However, analysis of single grain dose distributions requires knowledge of the dispersion of the well-bleached part of the dose distribution. This can be estimated by measurement of a suitable analogue, e.g. a well-bleached aeolian sample, but this requires such an analogue to be available, and in addition the assumptions that the sample is in fact a) well-bleached, and b) has a similar dose rate heterogeneity to the fossil deposit. Finally, it is an implicit assumption in such analysis that any over-dispersion is not significantly dose dependent. In this study we have undertaken laboratory investigations of the dose dependency of over-dispersion using a well-bleached modern sample with an average measured dose of 36 ± 3 mGy. This sample was prepared as heated (750 °C for 1 h), bleached and untreated portions which were then given uniform gamma doses ranging from 100 mGy to 208 Gy. We show that for these samples the relative laboratory over-dispersion is not constant as a function of dose and that the over-dispersion is smaller in heated samples. We also show that the dim grains in the distributions have a greater over-dispersion than the bright grains, implying that insensitive samples will have greater values of over-dispersion than sensitive samples.

Effects of Three Low-Doses of D-Tagatose on Glycemic Control Over Six Months in Subjects with Mild Type 2 Diabetes Mellitus Under Control with Diet and Exercise.

Science.gov (United States)

Ensor, Mark; Williams, Jarrod; Smith, Rebecca; Banfield, Amy; Lodder, Robert A

2014-10-01

The primary objective of this study was to evaluate the safety and the effect of D-tagatose on the glycemic control of subjects with type 2 diabetes as determined by HbA 1c levels at the end of 6 months of therapy using the subject's own baseline HbA 1c level as a comparator. The determination of the minimal dose required to cause a statistically significant reduction in HbA 1c was of particular interest. Eight weeks after screening, the qualifying subjects were randomized to receive one of three doses of D-tagatose: 2.5 g TID, 5.0 g TID or 7.5 g TID. Blood levels of HbA 1c , fasting blood glucose concentrations, plasma lipids, changes in body weight, changes in body mass index, and change in insulin levels were checked at each study visit and at the end of the study. Treatment success, as measured by the reduction of HbA 1c , was greatest for the 7.5 g D-tagatose dose group, although the difference between the treatments was not statistically significant. For fasting glucose, only the 7.5 g dosage group exhibited reductions from baseline at the 3- and 6-month time points. Mean body weights reduced in a dose-response fashion, with the 5.0 g and the 7.5 g D-tagatose doses providing the greatest reductions. D-tagatose at dosages of 2.5 g, 5.0 g, and 7.5 g TID for six months were well tolerated by this subject population. D-tagatose at 5.0 g TID was the minimal dose required to reduce HbA 1c . D-tagatose at 7.5 g TID provided the greatest effect in most measured efficacy parameters.

The predictive ability of six pharmacokinetic models of rocuronium developed using a single bolus: evaluation with bolus and continuous infusion regimen.

Science.gov (United States)

Sasakawa, Tomoki; Masui, Kenichi; Kazama, Tomiei; Iwasaki, Hiroshi

2016-08-01

Rocuronium concentration prediction using pharmacokinetic (PK) models would be useful for controlling rocuronium effects because neuromuscular monitoring throughout anesthesia can be difficult. This study assessed whether six different compartmental PK models developed from data obtained after bolus administration only could predict the measured plasma concentration (Cp) values of rocuronium delivered by bolus followed by continuous infusion. Rocuronium Cp values from 19 healthy subjects who received a bolus dose followed by continuous infusion in a phase III multicenter trial in Japan were used retrospectively as evaluation datasets. Six different compartmental PK models of rocuronium were used to simulate rocuronium Cp time course values, which were compared with measured Cp values. Prediction error (PE) derivatives of median absolute PE (MDAPE), median PE (MDPE), wobble, divergence absolute PE, and divergence PE were used to assess inaccuracy, bias, intra-individual variability, and time-related trends in APE and PE values. MDAPE and MDPE values were acceptable only for the Magorian and Kleijn models. The divergence PE value for the Kleijn model was lower than -10 %/h, indicating unstable prediction over time. The Szenohradszky model had the lowest divergence PE (-2.7 %/h) and wobble (5.4 %) values with negative bias (MDPE = -25.9 %). These three models were developed using the mixed-effects modeling approach. The Magorian model showed the best PE derivatives among the models assessed. A PK model developed from data obtained after single-bolus dosing can predict Cp values during bolus and continuous infusion. Thus, a mixed-effects modeling approach may be preferable in extrapolating such data.

Researches on Mathematical Relationship of Five Elements of Containing Notes and Fibonacci Sequence Modulo 5

Directory of Open Access Journals (Sweden)

Zhaoxue Chen

2015-01-01

Full Text Available Considering the five periods and six qi’s theory in TCM almost shares a common basis of stem-branch system with the five elements of containing notes, studying the principle or mathematical structure behind the five elements of containing notes can surely bring a novel view for the five periods and six qi’s researches. By analyzing typical mathematical rules included in He tu, Luo shu, and stem-branch theory in TCM as well as the Fibonacci sequence especially widely existent in the biological world, novel researches are performed on mathematical relationship between the five elements of containing notes and the Fibonacci sequence modulo 5. Enlightened by elementary Yin or Yang number grouping principle of He tu, Luo shu, the 12534 and 31542 key number series of Fibonacci sequence modulo 5 are obtained. And three new arrangements about the five elements of containing notes are then introduced, which have shown close relationship with the two obtained key subsequences of the Fibonacci sequence modulo 5. The novel discovery is quite helpful to recover the scientific secret of the five periods and six qi’s theory in TCM as well as that of whole traditional Chinese culture system, but more data is needed to elucidate the TCM theory further.

SU-E-T-279: Realization of Three-Dimensional Conformal Dose Planning in Prostate Brachytherapy

Energy Technology Data Exchange (ETDEWEB)

Li, Z; Jiang, S; Yang, Z [Tianjin University, Tianjin (China); Bai, H; Zhang, X [Seeds biological Pharmacy Ltd, Tianjin (China)

2014-06-01

Purpose: Successful clinical treatment in prostate brachytherapy is largely dependent on the effectiveness of pre-surgery dose planning. Conventional dose planning method could hardly arrive at a satisfy result. In this abstract, a three-dimensional conformal localized dose planning method is put forward to ensure the accuracy and effectiveness of pre-implantation dose planning. Methods: Using Monte Carlo method, the pre-calculated 3-D dose map for single source is obtained. As for multiple seeds dose distribution, the maps are combined linearly to acquire the 3-D distribution. The 3-D dose distribution is exhibited in the form of isodose surface together with reconstructed 3-D organs group real-timely. Then it is possible to observe the dose exposure to target volume and normal tissues intuitively, thus achieving maximum dose irradiation to treatment target and minimum healthy tissues damage. In addition, the exfoliation display of different isodose surfaces can be realized applying multi-values contour extraction algorithm based on voxels. The needles could be displayed in the system by tracking the position of the implanted seeds in real time to conduct block research in optimizing insertion trajectory. Results: This study extends dose planning from two-dimensional to three-dimensional, realizing the three-dimensional conformal irradiation, which could eliminate the limitations of 2-D images and two-dimensional dose planning. A software platform is developed using VC++ and Visualization Toolkit (VTK) to perform dose planning. The 3-D model reconstruction time is within three seconds (on a Intel Core i5 PC). Block research could be conducted to avoid inaccurate insertion into sensitive organs or internal obstructions. Experiments on eight prostate cancer cases prove that this study could make the dose planning results more reasonable. Conclusion: The three-dimensional conformal dose planning method could improve the rationality of dose planning by safely reducing

Evaluación de la nitazoxanida en dosis única y por tres días en parasitosis intestinal Nitazoxanide vs albendazole against intestinal parasites in a single dose and for three days

Directory of Open Access Journals (Sweden)

Uri Belkind-Valdovinos

2004-08-01

assess the efectiveness of the usual dose of nitazoxanide administered for three days and as a single dose for massive eradication of intestinal parasites in the pediatric population, compared with single-dose albendazole. MATERIAL AND METHODS: A randomized clinical trial was conducted in three rural communities in central Mexico City between 2001 and 2003 to assess three possible therapy regimes in a study population of 786 children 5 to 11 years of age, 92 of whom had a positive parasitology test result (15.1%. Group 1 included 27 patients treated with 400 mg given as a single dose of albendazole; group 2 included 34 patients whose therapy consisted of a 15 mg/kg/day dose for three consecutive days; patients in group 3 (n=31 were administered a single 1.2 g dose of nitazoxanide. Differences in proportions were assessed using Fisher's exact test. RESULTS: No statistically significant differences were found in the effectiveness of the three treatment regimes: 80.5% with albendazole, compared with the two nitazoxanide alternatives (67.6% and 71%, respectively. A higher prevalence of side effects was observed with nitazoxanide in the three-day regimen (26.5% and as a single dose (32.2%, compared with a single dose of albendazole (7.4%. CONCLUSIONS: According to the evidence on effectiveness and side effects, the use of nitazoxanide is not justified as a massive prophylactic medication for intestinal parasitosis control alternative in endemic areas. In countries with a high prevalence of intestinal parasitosis primary prevention measures should be the most important strategy, together with public sanitation, drinking water and sewage system availability, water chlorination, and appropriate animal fecal waste disposal, as well as health education.

Four-Dimensional Patient Dose Reconstruction for Scanned Ion Beam Therapy of Moving Liver Tumors

International Nuclear Information System (INIS)

Richter, Daniel; Saito, Nami; Chaudhri, Naved; Härtig, Martin; Ellerbrock, Malte; Jäkel, Oliver; Combs, Stephanie E.; Habermehl, Daniel; Herfarth, Klaus; Durante, Marco; Bert, Christoph

2014-01-01

Purpose: Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy. Methods and Materials: Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)–weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporal correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V 95 ) and 107% (V 107 ) of the planned doses. Results: 4D dose reconstruction based on daily measured data is possible in a clinical setting. V 95 and V 107 values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V 95 > 87%, SD < 3%) and overdose (mean V 107 < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients. Conclusions: A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment

A Three-period Samuelson-Diamond Growth Model

DEFF Research Database (Denmark)

Blomgren-Hansen, Niels

2005-01-01

Samuelson (1958) analyses a three-period model, whereas Diamod (1965) considers a two-period model. This difference poses the question whether the insights derived by analysing the simple two-period model carry over in the more complicated three-period case. They do. The Samuelson model (no produ...

Discrepancy between exercise performance, body composition, and sex steroid response after a six-week detraining period in professional soccer players.

Science.gov (United States)

Koundourakis, Nikolaos E; Androulakis, Nikolaos E; Malliaraki, Niki; Tsatsanis, Christos; Venihaki, Maria; Margioris, Andrew N

2014-01-01

The aim of this study was to examine the effects of a six-week off-season detraining period on exercise performance, body composition, and on circulating sex steroid levels in soccer players. Fifty-five professional male soccer players, members of two Greek Superleague Teams (Team A, n = 23; Team B, n = 22), participated in the study. The first two weeks of the detraining period the players abstained from any physical activity. The following four weeks, players performed low-intensity (50%-60% of VO2max) aerobic running of 20 to 30 minutes duration three times per week. Exercise performance testing, anthropometry, and blood sampling were performed before and after the six-week experimental period. Our data showed that in both teams A and B the six-week detraining period resulted in significant reductions in maximal oxygen consumption (60,31±2,52 vs 57,67±2,54; pperiod resulted in a rapid loss of exercise performance adaptations and optimal body composition status, but did not affect sex steroid resting levels. The insignificant changes in sex steroid concentration indicate that these hormones were a non-contributing parameter for the observed negative effects of detraining on exercise performance and body composition.

Perioperative single high dose ATG-Fresenius S administration as induction immunosuppressive therapy in cadaveric renal transplantation--preliminary results.

Science.gov (United States)

Samsel, R; Chmura, A; Włodarczyk, Z; Wyzgał, J; Cieciura, T; Lagiewska, B; Pliszczyński, J; Korczak, G; Lazowski, T; Paczek, L; Wałaszewski, J; Lao, M; Rowiński, W

1999-01-01

Monoclonal and polyclonal antilymphocyte antibodies have been used successfully in organ transplantation as induction therapy and in the treatment of acute graft rejection. Used for induction the medication is generally given for the first 7-10 days. The aim of this study was to assess the safety and efficacy of single high dose (9 mg/kg) ATG Fresenius S given perioperatively, before revascularization, to kidney allograft recipients. During last twelve months seventy six, first cadaveric kidney adult recipients were included into the study in two centers (center A-64, center B-12). All patients received triple drug immunosuppression (Neoral, steroids and Cellcept which was replaced by azathioprine after 4 months), and were randomized to receive ATG or not. The follow-up period ranged from 1 month up to 1 year. The preliminary results are very promising, the rejection rate in bolus group was significantly lower than in control. No significant side effects or serious adverse events in both groups were observed.

Comparative sequence analysis of nitrogen fixation-related genes in six legumes

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Dong Hyun eKim

2013-08-01

Full Text Available Legumes play an important role as food and forage crops in international agriculture especially in developing countries. Legumes have a unique biological process called nitrogen fixation (NF by which they convert atmospheric nitrogen to ammonia. Although legume genomes have undergone polyploidization, duplication and divergence, NF-related genes, because of their essential functional role for legumes, might have remained conserved. To understand the relationship of divergence and evolutionary processes in legumes, this study analyzes orthologs and paralogs for selected 20 NF-related genes by using comparative genomic approaches in six legumes i.e. Medicago truncatula (Mt, Cicer arietinum, Lotus japonicus, Cajanus cajan (Cc, Phaseolus vulgaris (Pv and Glycine max (Gm. Subsequently, sequence distances, numbers of synonymous substitutions per synonymous site (Ks and nonsynonymous substitutions per nonsynonymous site (Ka between orthologs and paralogs were calculated and compared across legumes. These analyses suggest the closest relationship between Gm and Cc and the farthest distance between Mt and Pv in 6 legumes. Ks proportional plots clearly showed ancient genome duplication in all legumes, whole genome duplication event in Gm and also speciation pattern in different legumes. This study also reported some interesting observations e.g. no peak at Ks 0.4 in Gm-Gm, location of two independent genes next to each other in Mt and low Ks values for outparalogs for three genes as compared to other 12 genes. In summary, this study underlines the importance of NF-related genes and provides important insights in genome organization and evolutionary aspects of six legume species analyzed.

Weight and body composition change over a six-week holiday period.

Science.gov (United States)

Wagner, D R; Larson, J N; Wengreen, H

2012-03-01

Change in weight and body composition was assessed over a six-week holiday period. Baseline testing occurred the Monday or Tuesday prior to Thanksgiving Day (November 24 or 25, 2008), and the post-holiday assessment was the Monday or Tuesday after New Year's Day (January 5 or 6, 2009). Thirteen men and 21 women ranging in age from 23-61 years completed the study. The majority of participants (24 of 34) perceived that they had gained weight, and four did gain ≥2 kg. However, despite some changes to dietary and exercise habits, on average there was no difference between pre-holiday weight (74.0±17.8 kg) and post-holiday weight (73.9±18.1 kg), nor between pre-holiday body fat percentage (25.4±9.0%) and post-holiday body fat percentage (25.4±8.9%). Despite a perception of substantial weight gain, body weight and body fat remained unchanged over a six-week holiday period.

Equivalence of a single dose (1200 mg) compared to a three-time a day dose (400 mg) of chondroitin 4&6 sulfate in patients with knee osteoarthritis. Results of a randomized double blind placebo controlled study.

Science.gov (United States)

Zegels, B; Crozes, P; Uebelhart, D; Bruyère, O; Reginster, J Y

2013-01-01

Evaluation of the efficacy and safety of a single oral dose of a 1200 mg sachet of chondroitin 4&6 sulfate (CS 1200) vs three daily capsules of chondroitin 4&6 sulfate 400 mg (CS 3*400) (equivalence study) and vs placebo (superiority study) during 3 months, in patients with knee osteoarthritis (OA). Comparative, double-blind, randomized, multicenter study, including 353 patients of both genders over 45 years with knee OA. Minimum inclusion criteria were a Lequesne index (LI) ≥ 7 and pain ≥ 40 mm on a visual analogue scale (VAS). LI and VAS were assessed at baseline and after 1-3 months. Equivalence between CS was tested using the per-protocol procedure and superiority of CS vs placebo was tested using an intent-to-treat procedure. After 3 months of follow-up, no significant difference was demonstrated between the oral daily single dose of CS 1200 formulation and the three daily capsules of CS 400. Patients treated with CS 1200 or CS 3*400 were significantly improved compared to placebo after 3 months of follow-up in terms of LI (security and tolerability was observed between the three groups. This study suggests that a daily administration of an oral sachet of 1200 mg of chondroitin 4&6 sulfate allows a significant clinical improvement compared to a placebo, and a similar improvement when compared to a regimen of three daily capsules of 400 mg of the same active ingredient. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Sequence comparison of the rDNA introns from six different species of Tetrahymena

DEFF Research Database (Denmark)

Nielsen, Henrik; Engberg, J

1985-01-01

model for the intron RNA of Cech et al. (Proc. Natl. Acad. Sci. U.S.A. 80, 3903 (83)). Most of the sequence variation in the four new sequences reported here is found in single stranded loops in the model. However, in four cases we found nucleotide substitutions in duplex stem regions, two of them...

Single Low Dose Primaquine (0.25 mg/kg Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects.

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Germana Bancone

Full Text Available Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75 mg/kg (adult dose 45 mg but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15-20% in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25 mg/kg (adult dose 15 mg to Artemisinin-based Combination Therapies (ACTs without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant approximates 15%.The tolerability and safety of primaquine (single dose 0.25 mg base/kg combined with dihydroartemisinin-piperaquine (DHA-PPQ given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5.0%, -4.2% and -4

Evaluation of the sterility of single-dose medications used in a multiple-dose fashion.

Science.gov (United States)

Martin, Elizabeth P; Mukherjee, Jean; Sharp, Claire R; Sinnott-Stutzman, Virginia B

2017-11-01

Bacterial proliferation was evaluated in single-dose medications used in a multi-dose fashion and when medications were intentionally inoculated with bacteria. Of 5 experimentally punctured medications, 1 of 75 vials (50% dextrose) became contaminated. When intentionally inoculated, hydroxyethyl starch and heparinized saline supported microbial growth. Based on these findings, it is recommended that hydroxyethyl starch and heparinized saline not be used in a multi-dose fashion.

Seroprevalence of transplacentally acquired measles antibodies in HIV-exposed versus HIV-unexposed infants at six months of age

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Sneha Jain

2017-01-01

Interpretation & conclusions: Most HEI lacked measles antibodies at six months age and were, therefore, more vulnerable to measles than HUnI. Seroconversion in response to a single dose of measles vaccine administered at six months age was low in these infants, signifying the need of additional dose(s of measles/measles-containing vaccine.

Time and dose-related changes in the thickness of pig skin after irradiation with single doses of 90Sr/90Y β-rays

International Nuclear Information System (INIS)

Rezvani, M.; Hamlet, R.; Hopewell, J.W.; Sieber, V.K.

1994-01-01

Time-related changes in pig skin thickness have been evaluated using a non-invasive ultrasound technique after exposure to a range of single doses of 90 Sr/ 90 Yr β-rays. The reduction in relative skin thickness developed in two distinct phases: the first was between 12 and 20 weeks postirradiation. No further changes were then seen until 52 weeks postirradiation when a second phase of skin thinning was observed. This was complete after 76 weeks and no further changes in relative skin thickness were seen in the maximum follow up period of 129 weeks. The timings of these phases of damage were independent of the radiation dose, however, the severity of both phases of radiation-induced skin thinning were dose related. (Author)

Single-dose-response curves of murine gastrointestinal crypt stem cells

International Nuclear Information System (INIS)

Masuda, K.; Withers, H.R.; Mason, K.A.; Chen, K.Y.

1977-01-01

Dose-response curves for the reproductive capacity of crypt stem cells of murine colonic, jejunal, and gastric mucosae exposed in situ to multifractionated gamma ray exposures were analyzed and single-dose-survival curves of these cells were constructed. The following conclusions were drawn: (1) The single-dose-response curves bend downward over a dose range of approximately 200 to 1500 rad; (2) cell death seems to be due to nonrepairable damage at doses less than 250 rad for colon, and 220 rad for jejunum; (3) there are 21, 110, and 140 stem cells per crypt of gastric, colonic, and jejunal mucosa, respectively; and (4) jejunal stem cells are the most radiosensitive and gastric mucosal stem cells are the most resistant

An explanation for the multiplicative and the additive dose-effect relationship with the single-hit model

International Nuclear Information System (INIS)

Kottbauer, M.M.; Fleck, C.M.; Schoellnberger, H.

1997-01-01

For solid tumors and for leukemia the excess cancer rate after a single radiation dose D is different. The multiplicative model describes the excess solid tumor probability rate which is proportional to the background rate of cancer and dependent on dose D. The additive model describes the excess probability rate for leukaemia which is proportional to the dose D but unrelated to the spontaneous rate of cancer. A second great difference between the two models is the duration of the increased cancer probability rate. The multiplicative mode predicts that the additional cancer risk persist the whole lifetime after exposure and the additive model predicts excess risk over a period of time. With the Single-hit model (SHM) which is a multistage cancer model both dose-response relationships can be described. It will be shown that only small differences in the derivation will lead to the different relationships. We then analyze the incidence data of leukemia (1950-1987) and of all solid tumors (1958-1987) of the atomic bomb survivors. (author)

Single-dose radiotherapy for painful bone metastases

International Nuclear Information System (INIS)

Kal, H.B.

1999-01-01

Background: External beam radiotherapy is frequently applied for palliative treatment of painful bone lesions with a variety of fractionation schemes. There is a continuous interest to administer only 1 or a few dose fractions for inducing pain relief. Methods: A review of the literature was made with the aim to determine whether a treatment can be deduced that is simple and effective. The linear-quadratic (L-Q) concept was applied to compare reported therapy schemes which each other for the iso-effect pain relief. Results: Single-dose and fractionated radiotherapy resulted in partial or complete pain relief in about 80% of the patients. Complete responses have been observed in about 43% of the patients. For patients responding to treatment, the duration of pain relief is at least 3 to 4 months with reported duration of up to 1 year or even longer. Conclusion: Based on this review of literature data concerning randomized trials a treatment with a single dose of 8 Gy is effective for inducing pain relief. (orig.) [de

Single-dose rofecoxib for acute postoperative pain in adults: a quantitative systematic review

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McQuay Henry J

2002-06-01

Full Text Available Abstract Background Rofecoxib is a cyclo-oxygenase 2 selective inhibitor. This systematic review of rofecoxib in acute pain examined studies in adults of analgesic efficacy over six hours, the amount and quality of the evidence on extended duration of analgesia, and the quality and quantity of evidence on adverse events. Methods Cochrane Library (issue 4, 2001, Biological Abstracts (March 2002, MEDLINE (March 2002 and PubMed (March 2002 were searched using rofecoxib as a free text term. The area under the pain relief versus time curve was dichotomized using validated equations to derive the proportion of patients on rofecoxib 50 mg or placebo with at least 50% pain relief over six hours. This was used to calculate the number needed to treat for at least 50% pain relief over six hours for rofecoxib compared with placebo. Information on duration of analgesia and adverse events was also collected. Results Five included trials investigated 1,118 patients, of whom 211 received placebo and 464 received rofecoxib 50 mg. The NNT for rofecoxib 50 mg was 2.3 (95% confidence interval 2.0 to 2.6. The weighted mean remedication time was 1.9 hours for placebo (126 patients, 7.4 hours for ibuprofen 400 mg (97 patients and 13.6 hours for rofecoxib 50 mg (322 patients. Conclusion Rofecoxib at 2–4 times the standard daily dose for chronic pain is an effective single dose oral analgesic in acute pain. Limitations in trial reporting constrain conclusions about longer duration of analgesia and adverse event profile.

Three-dimensional electron-beam dose calculations

International Nuclear Information System (INIS)

Shiu, A.S.

1988-01-01

The MDAH pencil-beam algorithm developed by Hogstrom et al (1981) has been widely used in clinics for electron-beam dose calculations for radiotherapy treatment planning. The primary objective of this research was to address several deficiencies of that algorithm and to develop an enhanced version. Two enhancements were incorporated into the pencil-beam algorithm; one models fluence rather than planar fluence, and the other models the bremsstrahlung dose using measured beam data. Comparisons of the resulting calculated dose distributions with measured dose distributions for several test phantoms have been made. From these results it is concluded (1) that the fluence-based algorithm is more accurate to use for the dose calculation in an inhomogeneous slab phantom, and (2) the fluence-based calculation provides only a limited improvement to the accuracy the calculated dose in the region just downstream of the lateral edge of an inhomogeneity. A pencil-beam redefinition model was developed for the calculation of electron-beam dose distributions in three dimensions

Single-fraction stereotactic radiotherapy: a dose-response analysis of arteriovenous malformation obliteration

International Nuclear Information System (INIS)

Touboul, Emmanuel; Al Halabi, Assem; Buffat, Laurent; Merienne, Louis; Huart, Judith; Schlienger, Michel; Lefkopoulos, Dimitrios; Mammar, Hamid; Missir, Odile; Meder, Jean-Francois; Laurent, Alex; Housset, Martin

1998-01-01

Purpose: Stereotactic radiotherapy delivered in a high-dose single fraction is an effective technique to obliterate intracranial arteriovenous malformations (AVM). To attempt to analyze the relationships between dose, volume, and obliteration rates, we studied a group of patients treated using single-isocenter treatment plans. Methods and Materials: From May 1986 to December 1989, 100 consecutive patients with angiographically proven AVM had stereotactic radiotherapy delivered as a high-dose single fraction using a single-isocenter technique. Distribution according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0 grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in 11, and large and irregular in 15. The targeted volume of the nidus was estimated using two-dimensional stereotactic angiographic data and, calculated as an ovoid-shaped lesion, was 1900 ± 230 mm 3 (median 968 mm 3 ; range 62-11, 250 mm 3 ). The mean minimum target dose (D min ) was 19 ± 0.6 Gy (median 20 Gy; range: 3-31.5). The mean volume within the isodose which corresponded to the minimum target dose was 2500 ± 300 mm 3 (median 1200 mm 3 ; range 75-14 900 mm 3 ). The mean maximum dose (D max ) was 34.5 ± 0.5 Gy (median 35 Gy; range 15-45). The mean angiographic follow-up was 42 ± 2.3 months (median 37.5; range 7-117). Results: The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate was 62.5 ± 7%. After univariate analysis, AVM obliteration was influenced by previous surgery (p = 0.0007), D min by steps of 5 Gy (p = 0.005), targeted volume of the nidus (≤968 mm 3 vs. >968 mm 3 ; p = 0.015), and grade according to Spetzler-Martin (grade 1-3 vs. grade 4-6; p = 0.011). After multivariate analysis, the independent factors influencing AVM obliteration were the D min [relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p min but does not seem to be influenced by D max and the targeted volume of the nidus

Genome sequences of six Phytophthora species associated with forests in New Zealand

Science.gov (United States)

Studholme, D.J.; McDougal, R.L.; Sambles, C.; Hansen, E.; Hardy, G.; Grant, M.; Ganley, R.J.; Williams, N.M.

2015-01-01

In New Zealand there has been a long association of Phytophthora diseases in forests, nurseries, remnant plantings and horticultural crops. However, new Phytophthora diseases of trees have recently emerged. Genome sequencing has been performed for 12 Phytophthora isolates, from six species: Phytophthora pluvialis, Phytophthora kernoviae, Phytophthora cinnamomi, Phytophthora agathidicida, Phytophthora multivora and Phytophthora taxon Totara. These sequences will enable comparative analyses to identify potential virulence strategies and ultimately facilitate better control strategies. This Whole Genome Shotgun data have been deposited in DDBJ/ENA/GenBank under the accession numbers LGTT00000000, LGTU00000000, JPWV00000000, JPWU00000000, LGSK00000000, LGSJ00000000, LGTR00000000, LGTS00000000, LGSM00000000, LGSL00000000, LGSO00000000, and LGSN00000000. PMID:26981359

Single-Shell Tank (SST) Retrieval Sequence Fiscal Year 2000 Update

International Nuclear Information System (INIS)

GARFIELD, J.S.

2000-01-01

This document describes the baseline single-shell tank (SST) waste retrieval sequence for the River Protection Project (RPP) updated for Fiscal Year 2000. The SST retrieval sequence identifies the proposed retrieval order (sequence), the tank selection and prioritization rationale, and planned retrieval dates for Hanford SSTs. In addition, the tank selection criteria and reference retrieval method for this sequence are discussed

Three dimensional periodic foundations for base seismic isolation

International Nuclear Information System (INIS)

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

2015-01-01

Based on the concept of phononic crystals, periodic foundations made of periodic materials are investigated in this paper. The periodic foundations can provide low frequency band gaps, which cover the main frequency ranges of seismic waves. Therefore, the periodic foundations are able to protect the upper structures during earthquake events. In this paper, the basic theory of three dimensional periodic foundations is studied and the finite element method was used to conduct the sensitivity study. A simplified three-dimensional periodic foundation with a superstructure was tested in the field and the feasibility of three dimensional periodic foundations was proved. The test results showed that the response of the upper structure with the three dimensional periodic foundation was reduced under excitation waves with the main frequency falling in the attenuation zones. The finite element analysis results are consistent with the experimental data, indicating that three dimensional periodic foundations are a feasible way of reducing seismic vibrations. (paper)

In vivo assessment of the tolerance dose of small liver volumes after single-fraction HDR irradiation

International Nuclear Information System (INIS)

Ricke, Jens; Seidensticker, Max; Luedemann, Lutz; Pech, Maciej; Wieners, Gero; Hengst, Susanne; Mohnike, Konrad; Cho, Chie Hee; Lopez Haenninen, Enrique; Al-Abadi, Hussain; Felix, Roland; Wust, Peter

2005-01-01

Purpose: To prospectively assess a dose-response relationship for small volumes of liver parenchyma after single-fraction irradiation. Methods and Materials: Twenty-five liver metastases were treated by computed tomography (CT)-guided interstitial brachytherapy. Magnetic resonance imaging was performed 1 day before and 3 days and 6, 12, and 24 weeks after therapy. MR sequences included T1-w gradient echo (GRE) enhanced by hepatocyte-targeted gadobenate dimeglumine. All MRI data sets were merged with 3D dosimetry data and evaluated by two radiologists. The reviewers indicated the border of hyperintensity on T2-w images (edema) or hypointensity on T1-w images (loss of hepatocyte function). Based on the total 3D data, a dose-volume histogram was calculated. We estimated the threshold dose for either edema or function loss as the D 90 , i.e., the dose achieved in at least 90% of the pseudolesion volume. Results: Between 3 days and 6 weeks, the extension of the edema increased significantly from the 12.9 Gy isosurface to 9.9 Gy (standard deviation [SD], 3.3 and 2.6). No significant change was detected between 6 and 12 weeks. After 24 weeks, the edematous tissue had shrunk significantly to 14.7 Gy (SD, 4.2). Three days postbrachytherapy, the D 90 for hepatocyte function loss reached the 14.9 Gy isosurface (SD, 3.9). At 6 weeks, the respective zone had increased significantly to 9.9 Gy (SD, 2.3). After 12 and 24 weeks, the dysfunction volume had decreased significantly to the 11.9 Gy and 15.2 Gy isosurface, respectively (SD, 3 and 4.1). Conclusions: The 95% interval from 7.6 to 12.2 Gy found as the minimal hepatocyte tolerance after 6 weeks accounts for the radiobiologic variations found in CT-guided brachytherapy, including heterogeneous dose rates by variable catheter arrays

Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

Science.gov (United States)

Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in

Single-cell sequencing to quantify genomic integrity in cancer

NARCIS (Netherlands)

van den Bos, Hilda; Bakker, Bjorn; Spierings, Diana C J; Lansdorp, Peter M; Foijer, Floris

The use of single-cell DNA sequencing (sc-seq) techniques for the diagnosis, prognosis and treatment of cancer is a rapidly developing field. Sc-seq research is gaining momentum by decreased sequencing costs and continuous improvements in techniques. In this review, we provide an overview of recent

Transcription blockage by homopurine DNA sequences: role of sequence composition and single-strand breaks

Science.gov (United States)

Belotserkovskii, Boris P.; Neil, Alexander J.; Saleh, Syed Shayon; Shin, Jane Hae Soo; Mirkin, Sergei M.; Hanawalt, Philip C.

2013-01-01

The ability of DNA to adopt non-canonical structures can affect transcription and has broad implications for genome functioning. We have recently reported that guanine-rich (G-rich) homopurine-homopyrimidine sequences cause significant blockage of transcription in vitro in a strictly orientation-dependent manner: when the G-rich strand serves as the non-template strand [Belotserkovskii et al. (2010) Mechanisms and implications of transcription blockage by guanine-rich DNA sequences., Proc. Natl Acad. Sci. USA, 107, 12816–12821]. We have now systematically studied the effect of the sequence composition and single-stranded breaks on this blockage. Although substitution of guanine by any other base reduced the blockage, cytosine and thymine reduced the blockage more significantly than adenine substitutions, affirming the importance of both G-richness and the homopurine-homopyrimidine character of the sequence for this effect. A single-strand break in the non-template strand adjacent to the G-rich stretch dramatically increased the blockage. Breaks in the non-template strand result in much weaker blockage signals extending downstream from the break even in the absence of the G-rich stretch. Our combined data support the notion that transcription blockage at homopurine-homopyrimidine sequences is caused by R-loop formation. PMID:23275544

Efficacy of a single dose of milbemycin oxime/praziquantel combination tablets, Milpro(®), against adult Echinococcus multilocularis in dogs and both adult and immature E. multilocularis in young cats.

Science.gov (United States)

Cvejic, Dejan; Schneider, Claudia; Fourie, Josephus; de Vos, Christa; Bonneau, Stephane; Bernachon, Natalia; Hellmann, Klaus

2016-03-01

Two single-site, laboratory, negatively controlled, masked, randomised dose confirmation studies were performed: one in dogs, the other in cats. After a period of acclimatisation, both the dogs and cats were orally infected with Echinococcus multilocularis protoscoleces. In the dog study, 10 dogs received a single dose of Milpro® tablets at a minimum dose of 0.5 mg/kg milbemycin oxime and 5 mg/kg praziquantel 18 days post-infection and 10 dogs received no treatment. In the cat study, 10 cats received a single dose of Milpro® tablets at a minimum dose of 2 mg/kg milbemycin oxime and 5 mg/kg praziquantel 7 days post-infection, 10 cats received a single dose of the treatment 18 days post-infection and 10 cats remained untreated. In both studies, intestinal worm counts were performed 23 days post-infection at necropsy. No worms were retrieved from any of the 30 treated animals. Nine of 10 control dogs had multiple worms (geometric mean 91, arithmetic mean 304) and all 10 control cats had multiple worms (geometric mean 216, arithmetic mean 481). The difference in worm counts between all three treated groups and their controls was highly significant (ANOVA p values of log transformed data dogs and cats as well as for elimination of immature E. multilocularis in cats as evidenced by the effectiveness of treatment 7 days post-infection. The treatments were well accepted and tolerated, and there were no adverse drug reactions observed.

Three years of seasonal dose assessment from outdoors gamma exposure in Sao Paulo city, Brazil

International Nuclear Information System (INIS)

Carneiro, Janete C.G.G.; Sanches, Matias P.; Betti, Flavio; Pecequilo, Brigitte R.S.

2011-01-01

Measurements of external (outdoors) gamma exposure from natural background radiation have been used to estimate the average annual doses in Sao Paulo city. Twelve monitoring stations were placed in different regions of the town including both urban (where building materials are present) and outskirts areas. Seasonally surveys observing the four seasons from 2008 to 2010 have been carried out. The data were drawn from a 3-month sampling using the thermoluminescent dosimetry. The effective doses values are quite similar (slightly higher during the winter), so it can be considered that these results are not under significant influence (or variability) of seasonal environmental conditions like temperature, wind or rain. Dose values over the three years period, from Vila Carrao district, exclusively an urban location with mostly no green areas, present the highest values, while the lower values were always obtained for Tucuruvi district, near the biggest urban forest, Parque Estadual da Cantareira. Over the assessed period, the mean of the average annual effective doses was 1.3 ± 0.1 mSv.y -1 . For the same period, the average annual background from nuclear and radioactive facility at IPEN was 0.75 ± 0.12 mSv.y -1 . (author)

Three years of seasonal dose assessment from outdoors gamma exposure in Sao Paulo city, Brazil

Energy Technology Data Exchange (ETDEWEB)

Carneiro, Janete C.G.G.; Sanches, Matias P.; Betti, Flavio; Pecequilo, Brigitte R.S., E-mail: janetegc@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2011-07-01

Measurements of external (outdoors) gamma exposure from natural background radiation have been used to estimate the average annual doses in Sao Paulo city. Twelve monitoring stations were placed in different regions of the town including both urban (where building materials are present) and outskirts areas. Seasonally surveys observing the four seasons from 2008 to 2010 have been carried out. The data were drawn from a 3-month sampling using the thermoluminescent dosimetry. The effective doses values are quite similar (slightly higher during the winter), so it can be considered that these results are not under significant influence (or variability) of seasonal environmental conditions like temperature, wind or rain. Dose values over the three years period, from Vila Carrao district, exclusively an urban location with mostly no green areas, present the highest values, while the lower values were always obtained for Tucuruvi district, near the biggest urban forest, Parque Estadual da Cantareira. Over the assessed period, the mean of the average annual effective doses was 1.3 {+-} 0.1 mSv.y{sup -1}. For the same period, the average annual background from nuclear and radioactive facility at IPEN was 0.75 {+-} 0.12 mSv.y{sup -1}. (author)

Analysis of resistance-associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents.

Science.gov (United States)

Eltahla, A A; Rodrigo, C; Betz-Stablein, B; Grebely, J; Applegate, T; Luciani, F; Schinkel, J; Dore, G J; Page, K; Bruneau, J; Morris, M D; Cox, A L; Kim, A Y; Shoukry, N H; Lauer, G M; Maher, L; Hellard, M; Prins, M; Lloyd, A R; Bull, R A

2017-01-01

Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naïve patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up. © 2016 John Wiley & Sons Ltd.

Dose response study of PVA-Fx gel for three dimensional dose distribution

International Nuclear Information System (INIS)

Brindha, S.; Ayyangar, Komanduri M.; Shen, Bin; Saw, Cheng B.

2001-01-01

Modern radiotherapy techniques involve complex field arrangements using conformal and intensity modulated radiation that requires three dimensional treatment planning. The verification of these plans poses even more challenge. In 1984, Gore et al., proposed that ferrous gel dosimeters combined with magnetic resonance imaging (MRI) could be used to measure three dimensional radiation dose distributions. Since then, there has been much interest in the development of gel dosimetry to aid the determination of three dimensional dose distributions during field arrangements. In this work, preparation and study of the MR characteristics of a PVA-Fx gel reported in the literature is presented

Hematological changes after single large dose half-body irradiation

International Nuclear Information System (INIS)

Herrmann, T.; Friedrich, S.; Jochem, I.; Eberhardt, H.J.; Koch, R.; Knorr, A.

1981-01-01

The determination of different peripheral blood parameters aimed at the study of side effects on the hematological cellular system following a 5 - 8 Gy single large dose half-body irradiation in 20 patients. Compared to the initial values the leukocytes between the 6. and 14., the thrombocytes between the 14. and 21. postirradiation day as well as the lymphocytes between 3 hours and 4 weeks postirradiation were significantly decreased without exhibiting complications such as hemorrhages or infections. The hemoglobin, hematocrit and reticulocyte values revealed but a slight decrease normalized within a 28 days postirradiation period. Transfusions were necessary when a tumor-caused anemia was present prior to irradiation. Changes in serum activity of aminotransferases and lactate dehydrogenase occured during the first hours after irradiation and were due to enzyme release from destroyed tumor cells

A Fuzzy Logic Based Three phase Inverter with Single DC Source for Grid Connected PV System Employing Three Phase Transformer

OpenAIRE

Mani, venkatesan; Ramachandran, Rajeswari; N, Deverajan

2016-01-01

A fuzzy based three phase inverter with single DC source for grid connected photo voltaic (PV) system employing three phase transformer is presented in this paper. Space Vector Pulse Width Modulation (SVPWM) control scheme is effectively used to generate the appropriate switching sequences to the inverter switches. The intend of the fuzzy logic approach is to meet high quality output, fast response and high robustness. Finally Total Harmonics Distortion (THD) generated by the inverter is comp...

Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity.

Science.gov (United States)

Reay, Jonathon L; Kennedy, David O; Scholey, Andrew B

2005-07-01

Single doses of the traditional herbal treatment Panax ginseng have recently been shown to elicit cognitive improvements in healthy young volunteers. The mechanisms by which ginseng improves cognitive performance are not known. However, they may be related to the glycaemic properties of some Panax species. Using a double-blind, placebo-controlled, balanced crossover design, 30 healthy young adults completed a 10 min test battery at baseline, and then six times in immediate succession commencing 60 min after the day's treatment (placebo, 200mg G115 or 400mg G115). The 10 min battery comprised a Serial Threes subtraction task (2 min); a Serial Sevens task (2 min); a Rapid Visual Information Processing task (5 min); then a 'mental fatigue' visual analogue scale. Blood glucose was measured prior to each day's treatment, and before, during and after the post-dose completions of the battery. Both the 200mg and 400mg treatments led to significant reductions in blood glucose levels at all three post-treatment measurements (p 0.005 in all cases). The most notable behavioural effects were associated with 200mg of ginseng and included significantly improved Serial Sevens subtraction task performance and significantly reduced subjective mental fatigue throughout all (with the exception of one time point in each case) of the post-dose completions of the 10 min battery (p 0.05). Overall these data suggest that Panax ginseng can improve performance and subjective feelings of mental fatigue during sustained mental activity. This effect may be related to the acute gluco-regulatory properties of the extract.

Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.

Science.gov (United States)

Derry, Christopher J; Derry, Sheena; Moore, R Andrew

2013-06-24

Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543

Single point estimation of phenytoin dosing: a reappraisal.

Science.gov (United States)

Koup, J R; Gibaldi, M; Godolphin, W

1981-11-01

A previously proposed method for estimation of phenytoin dosing requirement using a single serum sample obtained 24 hours after intravenous loading dose (18 mg/Kg) has been re-evaluated. Using more realistic values for the volume of distribution of phenytoin (0.4 to 1.2 L/Kg), simulations indicate that the proposed method will fail to consistently predict dosage requirements. Additional simulations indicate that two samples obtained during the 24 hour interval following the iv loading dose could be used to more reliably predict phenytoin dose requirement. Because of the nonlinear relationship which exists between phenytoin dose administration rate (RO) and the mean steady state serum concentration (CSS), small errors in prediction of the required RO result in much larger errors in CSS.

A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray.

Science.gov (United States)

Stott, C G; White, L; Wright, S; Wilbraham, D; Guy, G W

2013-04-01

To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, when administered to healthy male subjects. Twelve subjects took part in this fed-fasted cross-over study and received a single dose of THC/CBD spray (4 sprays = 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time-points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC). Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80-14.91 ng/ml) and lower in 5 subjects (2.81-3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97-9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0-t), AUC(0-inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2-2.5 h. Only mild adverse events were reported. The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.

Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

Science.gov (United States)

Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

2016-01-01

meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results We included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. Overall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence). When we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence). We conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings. Authors' conclusions Fixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB. PLAIN

Three-loop massive tadpoles and polylogarithms through weight six

Energy Technology Data Exchange (ETDEWEB)

Kniehl, B.A.; Pikelner, Andrey F.; Veretin, Oleg L. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

2017-05-15

We evaluate the three-loop massive vacuum bubble diagrams in terms of polylogarithms up to weight six. We also construct the basis of irrational constants being harmonic polylogarithms of arguments e{sup kiπ/3}.

Aging irradiation of polymers. Dose-rate and test sequence influence

International Nuclear Information System (INIS)

Alba, C.; Carlin, F.; Chenion, J.; Lemaire, F.; Le Meur, M.; Petitjean, M.

1984-05-01

This work brings up results of the irradiation dose-rate influence on mechanical and electrical properties of technical polymer materials evolution. Polymer samples were subjected to 3.3.10 -2 Gy.s -1 and 2.8.10 -1 Gy.s -1 dose-rate. Heat and radiation simultaneous action is usualy simulated sequentialy. The hardest simulation on the polymer is the sequence of irradiation followed by thermal aging not the reverse. This study was carried out on eight polymer materials among those used in the electrical appliances for P.W.R. nuclear power plants [fr

Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose.

Science.gov (United States)

Viscardi, Rose M; Othman, Ahmed A; Hassan, Hazem E; Eddington, Natalie D; Abebe, Elias; Terrin, Michael L; Kaufman, David A; Waites, Ken B

2013-05-01

Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial

Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis

Science.gov (United States)

Suputtamongkol, Yupin; Premasathian, Nalinee; Bhumimuang, Kid; Waywa, Duangdao; Nilganuwong, Surasak; Karuphong, Ekkapun; Anekthananon, Thanomsak; Wanachiwanawin, Darawan; Silpasakorn, Saowaluk

2011-01-01

Background Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined. Methods A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up. Results Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2–76) weeks in albendazole group, 39 (2–74) weeks in single dose ivermectin group, and 26 (2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin

Synthesis of a wild-type and three mutant Cucurbita maxima trypsin inhibitor-encoding genes by a single-strand approach.

Science.gov (United States)

Botes, D P; Qobose, M D; Corfield, V A

1991-09-15

A single-strand approach to gene assembly, based on a modification of an in vitro complementary oligodeoxyribonucleotide template-directed ligation of the desired sequence to a linearized vector [Chen et al., Nucleic Acids Res. 18 (1990) 871-878], is described. The gene coding for the wild-type Cucurbita maxima trypsin inhibitor of 29 amino acid residues [Bode et al., FEBS Lett. 242 (1989) 285-292], as well as three mutant forms of the gene, in which two of the three disulfide bonds have been replaced singly or as a pair, have been synthesized in a single synthesis run with minimal manual intervention. Subsequent to ligation to pUC9 and in vivo gapped duplex repair by Escherichia coli, their sequences have been verified.

Effect of gamma irradiation in vitro bulbiets storage ability and genetic variation of six garlic genotypes

International Nuclear Information System (INIS)

El-Sayed, S.F.; Gharib, A.A.; El-Shamy, M.R.; Abd El-Wadod, N.A.

2010-01-01

This investigation was carried out in the Tissue Culture Laboratory of Potato and Vegetatively Propagated Crops, Vegetable Research Department, Agricultural Research Center (A.R.C.), during the period of 2005-2008 to study the effect of different doses of gamma rays (0, 3, 5, 8, 10, 12 and 14 Gy) on the in vitro bulblets production from shoot basal plate (Sbp) explants of six garlic genotypes including three cultivars (Balady, American and Omani) and three clones (Sids-40, EgaSeedl and EgaSeed2) on a bulblets production medium (MS + 120 g/1 sucrose + 5 g/l activated charcoal + 0.1 mg BA/1). The present investigation also studied the storage ability of the in vitro produced bulblets stored in a growth chamber at 25° C during four months of storage. The random amplified polumorphic DNA (RAPD) analysis confirmed the genetic background of irradiated garlic genotypes. All garlic genotypes were able to produce bulblets from Sbp explants. At the end of storage period (4 months) the bulblets were healthy and suitable for cultivation in the field. RAPD analysis indicated that the six garlic genotypes are different in the number of bands and this was attributed to the gamma ray doses

Dose rate-dependent marrow toxicity of TBI in dogs and marrow sparing effect at high dose rate by dose fractionation.

Science.gov (United States)

Storb, R; Raff, R F; Graham, T; Appelbaum, F R; Deeg, H J; Schuening, F G; Sale, G; Seidel, K

1999-01-01

We evaluated the marrow toxicity of 200 and 300 cGy total-body irradiation (TBI) delivered at 10 and 60 cGy/min, respectively, in dogs not rescued by marrow transplant. Additionally, we compared toxicities after 300 cGy fractionated TBI (100 cGy fractions) to that after single-dose TBI at 10 and 60 cGy/min. Marrow toxicities were assessed on the basis of peripheral blood cell count changes and mortality from radiation-induced pancytopenia. TBI doses studied were just below the dose at which all dogs die despite optimal support. Specifically, 18 dogs were given single doses of 200 cGy TBI, delivered at either 10 (n=13) or 60 (n=5) cGy/min. Thirty-one dogs received 300 cGy TBI at 10 cGy/min, delivered as either single doses (n=21) or three fractions of 100 cGy each (n=10). Seventeen dogs were given 300 cGy TBI at 60 cGy/min, administered either as single doses (n=5) or three fractions of 100 cGy each (n=10). Within the limitations of the experimental design, three conclusions were drawn: 1) with 200 and 300 cGy single-dose TBI, an increase of dose rate from 10 to 60 cGy/min, respectively, caused significant increases in marrow toxicity; 2) at 60 cGy/min, dose fractionation resulted in a significant decrease in marrow toxicities, whereas such a protective effect was not seen at 10 cGy/min; and 3) with fractionated TBI, no significant differences in marrow toxicity were seen between dogs irradiated at 60 and 10 cGy/min. The reduced effectiveness of TBI when a dose of 300 cGy was divided into three fractions of 100 cGy or when dose rate was reduced from 60 cGy/min to 10 cGy/min was consistent with models of radiation toxicity that allow for repair of sublethal injury in DNA.

Sequence Dependent Interactions Between DNA and Single-Walled Carbon Nanotubes

Science.gov (United States)

Roxbury, Daniel

It is known that single-stranded DNA adopts a helical wrap around a single-walled carbon nanotube (SWCNT), forming a water-dispersible hybrid molecule. The ability to sort mixtures of SWCNTs based on chirality (electronic species) has recently been demonstrated using special short DNA sequences that recognize certain matching SWCNTs of specific chirality. This thesis investigates the intricacies of DNA-SWCNT sequence-specific interactions through both experimental and molecular simulation studies. The DNA-SWCNT binding strengths were experimentally quantified by studying the kinetics of DNA replacement by a surfactant on the surface of particular SWCNTs. Recognition ability was found to correlate strongly with measured binding strength, e.g. DNA sequence (TAT)4 was found to bind 20 times stronger to the (6,5)-SWCNT than sequence (TAT)4T. Next, using replica exchange molecular dynamics (REMD) simulations, equilibrium structures formed by (a) single-strands and (b) multiple-strands of 12-mer oligonucleotides adsorbed on various SWCNTs were explored. A number of structural motifs were discovered in which the DNA strand wraps around the SWCNT and 'stitches' to itself via hydrogen bonding. Great variability among equilibrium structures was observed and shown to be directly influenced by DNA sequence and SWCNT type. For example, the (6,5)-SWCNT DNA recognition sequence, (TAT)4, was found to wrap in a tight single-stranded right-handed helical conformation. In contrast, DNA sequence T12 forms a beta-barrel left-handed structure on the same SWCNT. These are the first theoretical indications that DNA-based SWCNT selectivity can arise on a molecular level. In a biomedical collaboration with the Mayo Clinic, pathways for DNA-SWCNT internalization into healthy human endothelial cells were explored. Through absorbance spectroscopy, TEM imaging, and confocal fluorescence microscopy, we showed that intracellular concentrations of SWCNTs far exceeded those of the incubation

Decoding sequence learning from single-trial intracranial EEG in humans.

Directory of Open Access Journals (Sweden)

Marzia De Lucia

Full Text Available We propose and validate a multivariate classification algorithm for characterizing changes in human intracranial electroencephalographic data (iEEG after learning motor sequences. The algorithm is based on a Hidden Markov Model (HMM that captures spatio-temporal properties of the iEEG at the level of single trials. Continuous intracranial iEEG was acquired during two sessions (one before and one after a night of sleep in two patients with depth electrodes implanted in several brain areas. They performed a visuomotor sequence (serial reaction time task, SRTT using the fingers of their non-dominant hand. Our results show that the decoding algorithm correctly classified single iEEG trials from the trained sequence as belonging to either the initial training phase (day 1, before sleep or a later consolidated phase (day 2, after sleep, whereas it failed to do so for trials belonging to a control condition (pseudo-random sequence. Accurate single-trial classification was achieved by taking advantage of the distributed pattern of neural activity. However, across all the contacts the hippocampus contributed most significantly to the classification accuracy for both patients, and one fronto-striatal contact for one patient. Together, these human intracranial findings demonstrate that a multivariate decoding approach can detect learning-related changes at the level of single-trial iEEG. Because it allows an unbiased identification of brain sites contributing to a behavioral effect (or experimental condition at the level of single subject, this approach could be usefully applied to assess the neural correlates of other complex cognitive functions in patients implanted with multiple electrodes.

Efficacy of various single-dose regimens of ceftriaxone in ...

African Journals Online (AJOL)

The therapeutic efficacy of single intramuscular doses of ceftriaxone (Rocephin; Roche) (62,S, 125 and 250 mg), administered without probenecid, was evaluated in 167 adult males with uncomplicated acute gonococcal urethritis. Cure rates of 100% were achieved at 62,5 mg and 250 mg. In the 125 mg dose group, ...

Time and dose-related changes in the thickness of pig skin after irradiation with single doses of [sup 90]Sr/[sup 90]Y [beta]-rays

Energy Technology Data Exchange (ETDEWEB)

Rezvani, M.; Hamlet, R.; Hopewell, J.W.; Sieber, V.K. (Churchill Hospital, Oxford (United Kingdom))

1994-04-01

Time-related changes in pig skin thickness have been evaluated using a non-invasive ultrasound technique after exposure to a range of single doses of [sup 90]Sr/[sup 90]Yr [beta]-rays. The reduction in relative skin thickness developed in two distinct phases: the first was between 12 and 20 weeks postirradiation. No further changes were then seen until 52 weeks postirradiation when a second phase of skin thinning was observed. This was complete after 76 weeks and no further changes in relative skin thickness were seen in the maximum follow up period of 129 weeks. The timings of these phases of damage were independent of the radiation dose, however, the severity of both phases of radiation-induced skin thinning were dose related. (Author).

SINGLE-DOSE VERSUS 3-DAY PROPHYLAXIS WITH CIPROFLOXACIN IN TRANSURETHRAL SURGERY - A CLINICAL-TRIAL

NARCIS (Netherlands)

BIJL, W; JANKNEGT, RA

1993-01-01

in 235 patients who underwent transurethral surgery, perioperative oral ciprofloxacin prophylaxis was given as a single dose 500 mg versus a 3-day regimen. Out of 180 evaluable patients, 84 received a single dose and 96 received a 3-day course. In the single dose prophylaxis group there were 5

Single dose total lymphoid irradiation combined with cyclophosphamide as immunosuppression for human marrow transplantation in aplastic anemia

International Nuclear Information System (INIS)

Kim, T.H.; Kersey, J.H.; Khan, F.M.; Sewchand, W.; Ramsey, N.; Krivit, W.; Coccia, P.; Nesbit, M.E.; Levitt, S.H.

1979-01-01

Six patients with aplastic anemia underwent bone marrow transplantation following conditioning with high dose cyclophosphamide and single dose total lymphoid irradiation with 750 rad, 26 rad/min at the midplane of the patient. They all received bone marrow from human leukocyte antigens/mixed lymphocyte culture (HLA/MLC) matched siblings. Five of 6 patients were alive without complications at 12, 11, 7, 4 and 4 months respectively. The remaining patient died from sepis which he had prior to transplantation. There were no graft rejection, graft-vs-Host Disease (GVHD) or interstitial pneumonitis among these patients. The procedure was well tolerated with minimal side effects. The results will be compared with those of groups whose bone marrow was previously transplanted with different immunosuppressive methods

Dose volume relationships for intraoperatively irradiated saphenous nerve

International Nuclear Information System (INIS)

Gillette, E.L.; Powers, B.E.; Gillette, S.M.; Thames, H.D.; Childs, G.; Vujaskovic, Z.; LaRue, S.M.

1995-01-01

Purpose/Objective: Intraoperative radiation therapy (IORT) is used to deliver high single doses of radiation to the tumor bed following surgical removal of various abdominal malignancies. The advantage of IORT is the ability to remove sensitive normal tissues from the treatment field and to limit the volume of normal tissue irradiated. The purpose of this study was to determine dose-volume relationships for retroperitoneal tissues. Materials and methods: 134 adult beagle dogs were irradiated to the surgically exposed paraaortic area. Normal tissues included in the treatment field were aorta, peripheral nerve, ureter, bone and muscle. Groups of 4 - 8 dogs were irradiated to doses ranging from 18 - 54 Gy for a 2x5 cm field, from 12 - 46 Gy for a 4x5 cm field, and 12 - 42 Gy to an 8x5 cm field. The radiations were done using 6 MeV electrons from a linear accelerator. Dogs were observed for three years after radiation. Electrophysiologic procedures were done prior to irradiation and annually following irradiation. The procedures included electromyography of the pelvic limb and paralumbar muscles supplied by the L1 to S1 spinal nerves to determine presence and degree of motor unit disease. Motor nerve conduction velocities of the proximal and distal sciatic nerves were determined. Sensory nerve conduction velocities of the saphenous nerve were also determined. Evoked lumbosacral and thoraco-lumbar spinal cord potentials were evaluated following stimulation of the left sciatic nerve. In addition to electrophysiologic studies, neurologic examinations were done prior to treatment and at six month intervals for the three year observation period. At the three year time period, dogs were euthanatized, sections of peripheral nerve taken, routinely processed, stained with Masson's trichrome and evaluated histomorphometrically using point count techniques. Results: Twenty-two dogs were euthanatized prior to the three year observation period due to peripheral nerve damage

Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults.

Science.gov (United States)

Barden, Jodie; Derry, Sheena; McQuay, Henry J; Moore, R Andrew

2009-10-07

Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis.Ketoprofen at doses between 12.5 mg and 100 mg produced NNTs for at least 50% pain relief over 4 to 6

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

International Nuclear Information System (INIS)

Lee, Eun-Jung; Kim, Jun Won; Yoo, Hyun; Kwak, Woori; Choi, Won Hoon; Cho, Seoae; Choi, Yu Jeong; Lee, Yoon-Jin; Cho, Jaeho

2015-01-01

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm 2 fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL-33

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

Energy Technology Data Exchange (ETDEWEB)

Lee, Eun-Jung, E-mail: forejs2@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kim, Jun Won, E-mail: JUNWON@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Yoo, Hyun, E-mail: gochunghee@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kwak, Woori, E-mail: asleo02@snu.ac.kr [Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-747 (Korea, Republic of); Choi, Won Hoon, E-mail: wonhoon@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Cho, Seoae, E-mail: seoae@cnkgenomics.com [C& K Genomics, Seoul National University Mt.4-2, Main Bldg. #514, SNU Research Park, NakSeoungDae, Gwanakgu, Seoul 151-919 (Korea, Republic of); Choi, Yu Jeong, E-mail: yunk9275@daum.net [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Yoon-Jin, E-mail: yjlee8@kirams.re.kr [Division of Radiation Effects, Research Center for Radiotherapy, Korea Institute of Radiological & Medical Sciences, Seoul 139-760 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

2015-08-14

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL

Single molecule sequencing-guided scaffolding and correction of draft assemblies.

Science.gov (United States)

Zhu, Shenglong; Chen, Danny Z; Emrich, Scott J

2017-12-06

Although single molecule sequencing is still improving, the lengths of the generated sequences are inevitably an advantage in genome assembly. Prior work that utilizes long reads to conduct genome assembly has mostly focused on correcting sequencing errors and improving contiguity of de novo assemblies. We propose a disassembling-reassembling approach for both correcting structural errors in the draft assembly and scaffolding a target assembly based on error-corrected single molecule sequences. To achieve this goal, we formulate a maximum alternating path cover problem. We prove that this problem is NP-hard, and solve it by a 2-approximation algorithm. Our experimental results show that our approach can improve the structural correctness of target assemblies in the cost of some contiguity, even with smaller amounts of long reads. In addition, our reassembling process can also serve as a competitive scaffolder relative to well-established assembly benchmarks.

Advances of Single-Cell Sequencing Technique in Tumors

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Ji-feng FENG

2017-03-01

Full Text Available With the completion of human genome project (HGP and the international HapMap project as well as rapid development of high-throughput biochip technology, whole genomic sequencing-targeted analysis of genomic structures has been primarily finished. Application of single cell for the analysis of the whole genomics is not only economical in material collection, but more importantly, the cell will be more purified, and the laboratory results will be more accurate and reliable. Therefore, exploration and analysis of hereditary information of single tumor cells has become the dream of all researchers in the field of basic research of tumors. At present, single-cell sequencing (SCS on malignancies has been widely used in the studies of pathogeneses of multiple malignancies, such as glioma, renal cancer and hematologic neoplasms, and in the studies of the metastatic mechanism of breast cancer by some researchers. This study mainly reviewed the SCS, the mechanisms and the methods of SCS in isolating tumor cells, and application of SCS technique in tumor-related basic research and clinical treatment.

Comparative molecular cytogenetics of major repetitive sequence families of three Dendrobium species (Orchidaceae) from Bangladesh

Science.gov (United States)

Begum, Rabeya; Alam, Sheikh Shamimul; Menzel, Gerhard; Schmidt, Thomas

2009-01-01

Background and Aims Dendrobium species show tremendous morphological diversity and have broad geographical distribution. As repetitive sequence analysis is a useful tool to investigate the evolution of chromosomes and genomes, the aim of the present study was the characterization of repetitive sequences from Dendrobium moschatum for comparative molecular and cytogenetic studies in the related species Dendrobium aphyllum, Dendrobium aggregatum and representatives from other orchid genera. Methods In order to isolate highly repetitive sequences, a c0t-1 DNA plasmid library was established. Repeats were sequenced and used as probes for Southern hybridization. Sequence divergence was analysed using bioinformatic tools. Repetitive sequences were localized along orchid chromosomes by fluorescence in situ hybridization (FISH). Key Results Characterization of the c0t-1 library resulted in the detection of repetitive sequences including the (GA)n dinucleotide DmoO11, numerous Arabidopsis-like telomeric repeats and the highly amplified dispersed repeat DmoF14. The DmoF14 repeat is conserved in six Dendrobium species but diversified in representative species of three other orchid genera. FISH analyses showed the genome-wide distribution of DmoF14 in D. moschatum, D. aphyllum and D. aggregatum. Hybridization with the telomeric repeats demonstrated Arabidopsis-like telomeres at the chromosome ends of Dendrobium species. However, FISH using the telomeric probe revealed two pairs of chromosomes with strong intercalary signals in D. aphyllum. FISH showed the terminal position of 5S and 18S–5·8S–25S rRNA genes and a characteristic number of rDNA sites in the three Dendrobium species. Conclusions The repeated sequences isolated from D. moschatum c0t-1 DNA constitute major DNA families of the D. moschatum, D. aphyllum and D. aggregatum genomes with DmoF14 representing an ancient component of orchid genomes. Large intercalary telomere-like arrays suggest chromosomal

Single dose oral ranitidine improves MRCP image quality: a double-blind study

International Nuclear Information System (INIS)

Bowes, M.T.; Martin, D.F.; Melling, A.; Roberts, D.; Laasch, H.-U.; Sukumar, S.; Morris, J.

2007-01-01

Aim: To investigate the possibility of whether a single 300 mg dose of ranitidine given orally 2-3 h before magnetic resonance cholangiopancreatography (MRCP) could reduce the signal from the stomach and duodenum, and thus increase the conspicuousness of the biliary tree. Materials and methods: Thirty-five volunteers (22 female, 13 male), (age range 21-50) were underwent MRCP in a double-blind, placebo-controlled, randomized, crossover trial on a Philips Intera 1.5 T machine using a phased array surface coil. Imaging was carried out in the coronal oblique plane. Six 40 mm sections were acquired at varying angles to delineate the biliary tree and pancreatic duct. The 70 examinations were blindly scored by three consultants experienced in cholangiography. Results: After ranitidine administration there was a significant decrease in signal from the stomach (mean = 17.7, p = 0.0005, CI 10, 25.3) and duodenum (mean = 18.4, p = 0.0005, 95%CI 9.6, 27.1) with a significant increase in conspicuousness of the distal common duct (mean = 7.7, p = 0.033, 95%CI 0.7, 14.7) and proximal common duct (mean = 8.7, p = 0.010 CI 2.2, 15.2). There were no adverse effects. Conclusion: Oral ranitidine is a cheap and effective agent to decrease signal from the upper gastrointestinal tract and to improve visibility of the biliary tree

Single event effects and total ionizing dose effects of typical VDMOSFET devices

International Nuclear Information System (INIS)

Lou Jianshe; Cai Nan; Liu Jiaxin; Wu Qinzhi; Wang Jia

2012-01-01

In this work, single event effects and total ionizing dose effects of typical VDMOSFET irradiated by 60 Co γ-rays and 252 Cf source were studied. The single event burnout and single event gate rupture (SEB/SEGR) effects were investigated, and the relationship between drain-source breakdown voltage and ionizing dose was obtained. The results showed that the VDMOSFET devices were sensitive to SEB and SEGR, and measures to improve their resistance to SEB and SEGR should be considered seriously for their space applications. The drain-source breakdown voltage was sensitive to total ionizing dose effects as the threshold voltage. In assessing the devices' resistance to the total ionizing dose effects, both the threshold voltage and the drain-source breakdown voltage should be taken into account. (authors)

The evolution of anti-ulcer therapy with cimetidine. Is a single large nocturnal dose of cimetidine the right therapy for duodenal ulcer?

Science.gov (United States)

Barbara, L; Corinaldesi, B; Stanghellini, V; Paternicò, A; Fabbri, L; Sacco, T

1986-01-01

Peptic ulcer results from the prevalence of agents causing endoluminal lesions over the defence mechanisms of the mucosa of the upper GI tract. Particularly, in the case of duodenal ulcer, the pathogenetic relevance of non-buffered acid secretion of the early nighttime period has been emphasized. This is indeed confirmed by the fact that a single night dose of 800 mg cimetidine has apparently been proved able--in numerous controlled clinical trials--to provide results that are similar to those obtained with the classic dose of 1 g daily or 400 mg twice daily. Our centre carried out a crossover double-blind controlled trial aimed at evaluating titrable acidity and pH during the 24-h period in seven patients with active duodenal ulcer. The single nighttime dose of cimetidine resulted in a significant and long-lasting inhibition of acid secretion during the entire night. During the day, secretory values returned to levels similar to those obtained with placebo, hence allowing normal digestive functions.

Three and six grams supplementation of d-aspartic acid in resistance trained men.

Science.gov (United States)

Melville, Geoffrey W; Siegler, Jason C; Marshall, Paul Wm

2015-01-01

Although abundant research has investigated the hormonal effects of d-aspartic acid in rat models, to date there is limited research on humans. Previous research has demonstrated increased total testosterone levels in sedentary men and no significant changes in hormonal levels in resistance trained men. It was hypothesised that a higher dosage may be required for experienced lifters, thus this study investigated the effects of two different dosages of d-aspartic acid on basal hormonal levels in resistance trained men and explored responsiveness to d-aspartic acid based on initial testosterone levels. Twenty-four males, with a minimum of two years' experience in resistance training, (age, 24.5 ± 3.2 y; training experience, 3.4 ± 1.4 y; height, 178.5 ± 6.5 cm; weight, 84.7 ± 7.2 kg; bench press 1-RM, 105.3 ± 15.2 kg) were randomised into one of three groups: 6 g.d(-1) plain flour (D0); 3 g.d(-1) of d-aspartic acid (D3); and 6 g.d(-1) of d-aspartic acid (D6). Participants performed a two-week washout period, training four days per week. This continued through the experimental period (14 days), with participants consuming the supplement in the morning. Serum was analysed for levels of testosterone, estradiol, sex hormone binding globulin, albumin and free testosterone was determined by calculation. D-aspartic acid supplementation revealed no main effect for group in: estradiol; sex-hormone-binding-globulin; and albumin. Total testosterone was significantly reduced in D6 (P = 0.03). Analysis of free testosterone showed that D6 was significantly reduced as compared to D0 (P = 0.005), but not significantly different to D3. Analysis did not reveal any significant differences between D3 and D0. No significant correlation between initial total testosterone levels and responsiveness to d-aspartic acid was observed (r = 0.10, P = 0.70). The present study demonstrated that a daily dose of six grams of d-aspartic acid decreased

Effect of the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan on the pharmacokinetics and pharmacodynamics of a single dose of furosemide

Science.gov (United States)

Ayalasomayajula, Surya; Schuehly, Uwe; Pal, Parasar; Chen, Fabian; Zhou, Wei; Sunkara, Gangadhar

2018-01-01

Aims Sacubitril/valsartan is indicated for the treatment of heart failure and reduced ejection fraction (HFrEF). Furosemide, a loop diuretic commonly used for the treatment of HFrEF, may be coadministered with sacubitril/valsartan in clinical practice. The effect of sacubitril/valsartan on the pharmacokinetics and pharmacodynamics of furosemide was evaluated in this open label, two‐period, single‐sequence study in healthy subjects. Methods All subjects (n = 28) received 40 mg oral single‐dose furosemide during period 1, followed by a washout of 2 days. In period 2, sacubitril/valsartan 200 mg (97/103 mg) was administered twice daily for 5 days and a single dose of 40 mg furosemide was coadministered on day 6. Serial plasma and urine samples were collected to determine the pharmacokinetics of furosemide and sacubitril/valsartan and the pharmacodynamics of furosemide. The point estimates and the associated 90% confidence intervals for pharmacokinetic parameters were evaluated. Results Coadministration of furosemide with sacubitril/valsartan decreased the maximum observed plasma concentration (Cmax) [estimated geometric mean ratio (90% confidence interval): 0.50 (0.44, 0.56)], area under the plasma concentration–time curve (AUC) from time 0 to infinity [0.72 (0.67, 0.77)] and 24‐h urinary excretion of furosemide [0.74 (0.69, 0.79)]. When coadministered with sacubitril/valsartan, 0–4‐h, 4–8‐h and 0–24‐h diuresis in response to furosemide was reduced by ~7%, 21% and 0.2%, respectively, while natriuresis was reduced by ~ 28.5%, 7% and 15%, respectively. Post hoc analysis of the pivotal phase III Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF) indicated that the median furosemide dose was similar at baseline and at the end of the study in the sacubitril/valsartan group. Conclusions Sacubitril/valsartan reduced plasma Cmax and AUC and 24‐h urinary excretion

Estimated radiation doses to different organs among patients treated for ankylosing spondylitis with a single course of X rays

International Nuclear Information System (INIS)

Lewis, C.A.; Smith, P.G.; Stratton, I.M.; Darby, S.C.; Doll, R.

1988-01-01

A follow-up study of over 14000 patients treated with a single course of X rays for ankylosing spondylitis demonstrated substantial excess risk of developing cancer. Previously the excess risk of leukaemia has been related to the estimated mean radiation dose to active bone marrow but detailed estimates were not made of the radiation doses to other organs. Data extracted from the original treatment records of a random sample of one in 15 patients have been used to make dose estimates, using Monte Carlo methods, for 30 specific organs or body regions and 12 bone marrow sites. Estimates of mean and median organ doses, standard deviations and ranges have been tabulated. Detailed distributions are presented for six organs (lung, bronchi, stomach, oesophagus, active bone marrow and total body). Comparison with the earlier bone marrow estimates and more recent theoretical estimates shows good agreement. (author)

Independent dose per monitor unit review of eight U.S.A. proton treatment facilities

International Nuclear Information System (INIS)

Moyers, M. F.; Ibbott, G. S.; Grant, R. L.; Summers, P. A.; Followill, D. S.

2014-01-01

Purpose: Compare the dose per monitor unit at different proton treatment facilities using three different dosimetry methods. Methods: Measurements of dose per monitor unit were performed by a single group at eight facilities using 11 test beams and up to six different clinical portal treatment sites. These measurements were compared to the facility reported dose per monitor unit values. Results: Agreement between the measured and reported doses was similar using any of the three dosimetry methods. Use of the ICRU 59 N D,w based method gave results approximately 3% higher than both the ICRU 59 N X and ICRU 78 (TRS-398) N D,w based methods. Conclusions: Any single dosimetry method could be used for multi-institution trials with similar conformity between facilities. A multi-institutional trial could support facilities using both the ICRU 59 N X based and ICRU 78 (TRS-398) N D,w based methods but use of the ICRU 59 N D,w based method should not be allowed simultaneously with the other two until the difference is resolved

MECHANICAL CHARACTERISTICS OF THREE-PHASE INDUCTION MOTORS WITH SINGLE-PHASE POWER SUPPLY

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V.S. Malyar

2016-06-01

Full Text Available Aim. Development of a method for calculating mechanical characteristics of three-phase induction motors with single-phase power supply. Methods. The developed algorithm is based on the high-adequacy mathematical model of motor and projection method for solving the boundary problem for equations of electrical circuits balance presented in the three-phase coordinate system. As a result of asymmetry of power supply to the stator windings, in steady state, flux-linkage and current change according to the periodic law. They are determined by solving the boundary problem. Results. The developed mathematical model allows determining periodic dependence of coordinates as a function of slip and, based on them, mechanical characteristics of motors. Academic novelty. The developed method relies on a completely new mathematical approach to calculation of stationary modes of nonlinear electromagnetic circuits, which allows obtaining periodic solution in a timeless domain. Practical value. Using the developed calculation algorithm, one can select capacitance required to start an induction motor with single-phase power supply and calculate static mechanical characteristics at a given capacitance.

Patch test dose-response study: polysensitized individuals do not express lower elicitation thresholds than single/double-sensitized individuals

DEFF Research Database (Denmark)

Carlsen, B C; Fischer, Louise Arup; Sosted, H

2009-01-01

with nickel sulphate, methyldibromo glutaronitrile (MDBGN) and p-phenylenediamine (PPD) in dilution series. The ratio between the doses eliciting a response in 50% of patients in the two groups was used as the measure for relative sensitivity. RESULTS: The dose-response curves of the polysensitized group...... for MDBGN and PPD were shifted to the right, and for nickel sulphate shifted to the left, compared with the single/double-sensitized group. The relative sensitivity for each of the three allergens and a combined relative sensitivity for all three allergens were not significantly different when comparing...

Population structure and genetic diversity of Indian Major Carp, Labeo rohita (Hamilton, 1822) from three phylo-geographically isolated riverine ecosystems of India as revealed by mtDNA cytochrome b region sequences.

Science.gov (United States)

Behera, Bijay Kumar; Baisvar, Vishwamitra Singh; Kunal, Swaraj Priyaranjan; Meena, Dharmendra Kumar; Panda, Debarata; Pakrashi, Sudip; Paria, Prasenjit; Das, Pronob; Bhakta, Dibakar; Debnath, Dipesh; Roy, Suvra; Suresh, V R; Jena, J K

2018-03-01

The population structure and genetic diversity of Rohu (Labeo rohita Hamilton, 1822) was studied by analysis of the partial sequences of mitochondrial DNA cytochrome b region. We examined 133 samples collected from six locations in three geographically isolated rivers of India. Analysis of 11 haplotypes showed low haplotype diversity (0.00150), nucleotide diversity (π) (0.02884) and low heterogeneity value (0.00374). Analysis of molecular variance (AMOVA) revealed the genetic diversity of L. rohita within population is very high than between the populations. The Fst scores (-0.07479 to 0.07022) were the indication of low genetic structure of L. rohita populations of three rivers of India. Conspicuously, Farakka-Bharuch population pair Fst score of 0.0000, although the sampling sites are from different rivers. The phylogenetic reconstruction of unique haplotypes revealed sharing of a single central haplotype (Hap_1) by all the six populations with a point mutations ranging from 1-25 nucleotides.

Separate assessment of natural beta and gamma dose-rates with TL from α-Al2O3:C single-crystal chips

International Nuclear Information System (INIS)

Kalchgruber, R.; Wagner, G.A.

2006-01-01

A measurement procedure was developed for fast and separate assessment of beta and gamma dose-rates in natural sediments using highly sensitive α-Al 2 O 3 :C single-crystal chips. The dosemeters were buried for periods from two days to three weeks in sediments with different layer structure and homogeneity. For each measurement, a pair of dosemeters was buried, in order to assess beta and gamma dose-rates separately. One dosemeter was wrapped only in thin plastic foil to shield it from alpha radiation, thus measuring beta + gamma components. The second one, used for the gamma component only, was packed additionally in a 1mm copper container for absorption of beta radiation. For calibration, another set of dosemeters was buried in reference soil with a well-known dose-rate and similar content of radioactive nuclides. By comparing the thermally stimulated luminescence signals from the dosemeters the gamma dose-rate and also, by subtraction, the beta dose-rate in the unknown soil could be determined. The calculated uncertainties were 5-7% and 10%, respectively. The resulting dose-rates for homogeneous and inhomogeneous media were compared with the results obtained by Ge- and on-site NaI-gamma-ray spectrometry. An agreement within 2σ-error limits was found for homogeneous media after only few days of exposure

Generation and analysis of expressed sequence tags from six developing xylem libraries in Pinus radiata D. Don

Directory of Open Access Journals (Sweden)

Dillon Shannon K

2009-01-01

Full Text Available Abstract Background Wood is a major renewable natural resource for the timber, fibre and bioenergy industry. Pinus radiata D. Don is the most important commercial plantation tree species in Australia and several other countries; however, genomic resources for this species are very limited in public databases. Our primary objective was to sequence a large number of expressed sequence tags (ESTs from genes involved in wood formation in radiata pine. Results Six developing xylem cDNA libraries were constructed from earlywood and latewood tissues sampled at juvenile (7 yrs, transition (11 yrs and mature (30 yrs ages, respectively. These xylem tissues represent six typical development stages in a rotation period of radiata pine. A total of 6,389 high quality ESTs were collected from 5,952 cDNA clones. Assembly of 5,952 ESTs from 5' end sequences generated 3,304 unigenes including 952 contigs and 2,352 singletons. About 97.0% of the 5,952 ESTs and 96.1% of the unigenes have matches in the UniProt and TIGR databases. Of the 3,174 unigenes with matches, 42.9% were not assigned GO (Gene Ontology terms and their functions are unknown or unclassified. More than half (52.1% of the 5,952 ESTs have matches in the Pfam database and represent 772 known protein families. About 18.0% of the 5,952 ESTs matched cell wall related genes in the MAIZEWALL database, representing all 18 categories, 91 of all 174 families and possibly 557 genes. Fifteen cell wall-related genes are ranked in the 30 most abundant genes, including CesA, tubulin, AGP, SAMS, actin, laccase, CCoAMT, MetE, phytocyanin, pectate lyase, cellulase, SuSy, expansin, chitinase and UDP-glucose dehydrogenase. Based on the PlantTFDB database 41 of the 64 transcription factor families in the poplar genome were identified as being involved in radiata pine wood formation. Comparative analysis of GO term abundance revealed a distinct transcriptome in juvenile earlywood formation compared to other stages of

Generation of brain pseudo-CTs using an undersampled, single-acquisition UTE-mDixon pulse sequence and unsupervised clustering

International Nuclear Information System (INIS)

Su, Kuan-Hao; Hu, Lingzhi; Traughber, Melanie; Stehning, Christian; Helle, Michael; Qian, Pengjiang; Thompson, Cheryl L.; Pereira, Gisele C.; Traughber, Bryan J.; Jordan, David W.; Herrmann, Karin A.; Muzic, Raymond F.

2015-01-01

Purpose: MR-based pseudo-CT has an important role in MR-based radiation therapy planning and PET attenuation correction. The purpose of this study is to establish a clinically feasible approach, including image acquisition, correction, and CT formation, for pseudo-CT generation of the brain using a single-acquisition, undersampled ultrashort echo time (UTE)-mDixon pulse sequence. Methods: Nine patients were recruited for this study. For each patient, a 190-s, undersampled, single acquisition UTE-mDixon sequence of the brain was acquired (TE = 0.1, 1.5, and 2.8 ms). A novel method of retrospective trajectory correction of the free induction decay (FID) signal was performed based on point-spread functions of three external MR markers. Two-point Dixon images were reconstructed using the first and second echo data (TE = 1.5 and 2.8 ms). R2 ∗ images (1/T2 ∗ ) were then estimated and were used to provide bone information. Three image features, i.e., Dixon-fat, Dixon-water, and R2 ∗ , were used for unsupervised clustering. Five tissue clusters, i.e., air, brain, fat, fluid, and bone, were estimated using the fuzzy c-means (FCM) algorithm. A two-step, automatic tissue-assignment approach was proposed and designed according to the prior information of the given feature space. Pseudo-CTs were generated by a voxelwise linear combination of the membership functions of the FCM. A low-dose CT was acquired for each patient and was used as the gold standard for comparison. Results: The contrast and sharpness of the FID images were improved after trajectory correction was applied. The mean of the estimated trajectory delay was 0.774 μs (max: 1.350 μs; min: 0.180 μs). The FCM-estimated centroids of different tissue types showed a distinguishable pattern for different tissues, and significant differences were found between the centroid locations of different tissue types. Pseudo-CT can provide additional skull detail and has low bias and absolute error of estimated CT

Fast convergence of spike sequences to periodic patterns in recurrent networks

International Nuclear Information System (INIS)

Jin, Dezhe Z.

2002-01-01

The dynamical attractors are thought to underlie many biological functions of recurrent neural networks. Here we show that stable periodic spike sequences with precise timings are the attractors of the spiking dynamics of recurrent neural networks with global inhibition. Almost all spike sequences converge within a finite number of transient spikes to these attractors. The convergence is fast, especially when the global inhibition is strong. These results support the possibility that precise spatiotemporal sequences of spikes are useful for information encoding and processing in biological neural networks

Bifurcations and degenerate periodic points in a three dimensional chaotic fluid flow

International Nuclear Information System (INIS)

Smith, L. D.; Rudman, M.; Lester, D. R.; Metcalfe, G.

2016-01-01

Analysis of the periodic points of a conservative periodic dynamical system uncovers the basic kinematic structure of the transport dynamics and identifies regions of local stability or chaos. While elliptic and hyperbolic points typically govern such behaviour in 3D systems, degenerate (parabolic) points also play an important role. These points represent a bifurcation in local stability and Lagrangian topology. In this study, we consider the ramifications of the two types of degenerate periodic points that occur in a model 3D fluid flow. (1) Period-tripling bifurcations occur when the local rotation angle associated with elliptic points is reversed, creating a reversal in the orientation of associated Lagrangian structures. Even though a single unstable point is created, the bifurcation in local stability has a large influence on local transport and the global arrangement of manifolds as the unstable degenerate point has three stable and three unstable directions, similar to hyperbolic points, and occurs at the intersection of three hyperbolic periodic lines. The presence of period-tripling bifurcation points indicates regions of both chaos and confinement, with the extent of each depending on the nature of the associated manifold intersections. (2) The second type of bifurcation occurs when periodic lines become tangent to local or global invariant surfaces. This bifurcation creates both saddle–centre bifurcations which can create both chaotic and stable regions, and period-doubling bifurcations which are a common route to chaos in 2D systems. We provide conditions for the occurrence of these tangent bifurcations in 3D conservative systems, as well as constraints on the possible types of tangent bifurcation that can occur based on topological considerations.

Unravelling biology and shifting paradigms in cancer with single-cell sequencing.

Science.gov (United States)

Baslan, Timour; Hicks, James

2017-08-24

The fundamental operative unit of a cancer is the genetically and epigenetically innovative single cell. Whether proliferating or quiescent, in the primary tumour mass or disseminated elsewhere, single cells govern the parameters that dictate all facets of the biology of cancer. Thus, single-cell analyses provide the ultimate level of resolution in our quest for a fundamental understanding of this disease. Historically, this quest has been hampered by technological shortcomings. In this Opinion article, we argue that the rapidly evolving field of single-cell sequencing has unshackled the cancer research community of these shortcomings. From furthering an elemental understanding of intra-tumoural genetic heterogeneity and cancer genome evolution to illuminating the governing principles of disease relapse and metastasis, we posit that single-cell sequencing promises to unravel the biology of all facets of this disease.

Functional and morphological changes in pig skin after single or fractionated doses in x rays

International Nuclear Information System (INIS)

Young, C.M.A.; Hopewell, J.W.

1982-01-01

The flank skin of pigs has been treated with either single or fractionated doses of x-irradiation. A single dose (2070 cGy) was compared with treatment given as 6 fractions in 18 days (6f/18 days; 3780 cGy) or 30 fractions in 39 days (30f/39 days; 8000 cGy). The doses were selected on the basis that similar levels of late tissue damage would result. Radiation induced changes in the skin were assessed by observing the skin reactions and by the measurement of isotope clearance (functional study), relative field contraction, dermal and epidermal thickness and dermal vascular density (morphological studies). In the three treatment groups the early radiation reaction varied considerably. In the first wave reaction (3 to 6 weeks after treatment) bright red erythema was recorded in many fields but moist desquamation developed only in the 30f/39 days treatment group. The second wave (10-16 weeks) was characterized by an ischemic mauve/dusky reaction. Dermal necrosis developed in 50% of the single dose fields. In the 30f/39 days regimen persistent moist desquamation progressed to dermal necrosis. Neither desquamation nor necrosis developed after 6f/18 days. Different levels of vascular damage in the dermis were assessed using an isotope clearance technique; for example in the early reaction significant changes were recorded in the papillary dermis (faster clearance) prior to the development of moist desquamation (30f/39 days) and in the reticular dermis (slower clearance) before necrosis (single dose). Changes in clearance rates have been correlated with changes in the vascular density and thickness of the dermis. Between 26 and 52 weeks (the late reaction) relative field contraction was slightly greater in the 30f/39 days group than in the other treatment groups

Lithium clearance method and the renal response to low-dose dopamine in man

DEFF Research Database (Denmark)

Olsen, N V; Olsen, M H; Fogh-Andersen, N

1993-01-01

.00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1h baseline period and three 1h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 +/- 0.35 ml/min, but with lithium......-induced changes in effective renal plasma flow, glomerular filtration rate or osmolal clearance. Neither lithium nor dopamine influenced plasma concentrations of renin, aldosterone or atrial natriuretic peptide. 4. In conclusion, single test doses of lithium, as normally used in lithium clearance studies......1. The effect of a single dose of lithium on renal function before and during intravenous infusion of dopamine (3 micrograms min-1 kg-1) was investigated in 12 healthy males. In a double-blind and randomized design, 450mg or 600mg of lithium carbonate or placebo was administered orally at 22...

Lithium clearance method and the renal response to low-dose dopamine in man

DEFF Research Database (Denmark)

Olsen, Niels Vidiendal; Olsen, M H; Fogh-Andersen, N

1993-01-01

.00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1h baseline period and three 1h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 +/- 0.35 ml/min, but with lithium...... in effective renal plasma flow, glomerular filtration rate or osmolal clearance. Neither lithium nor dopamine influenced plasma concentrations of renin, aldosterone or atrial natriuretic peptide. 4. In conclusion, single test doses of lithium, as normally used in lithium clearance studies, increase baseline......1. The effect of a single dose of lithium on renal function before and during intravenous infusion of dopamine (3 micrograms min-1 kg-1) was investigated in 12 healthy males. In a double-blind and randomized design, 450mg or 600mg of lithium carbonate or placebo was administered orally at 22...

Iron concentration in breast milk normalised within one week of a single high-dose infusion of iron isomaltoside in randomised controlled trial

DEFF Research Database (Denmark)

Holm, Charlotte; Thomsen, Lars Lykke; Nørgaard, Astrid

2017-01-01

AIM: We compared the iron concentration in breast milk after a single high-dose of intravenous iron isomaltoside or daily oral iron for postpartum haemorrhage. METHODS: In this randomised controlled trial, the women were allocated a single dose of intravenous 1,200mg iron isomaltoside or oral iron...... deviation) iron concentration in breast milk in the intravenous and oral groups were 0.72 ± 0.27 mg/L and 0.40 ± 0.18 mg/L at three days (p birth. CONCLUSION: A single high...

Quantum Point Contact Single-Nucleotide Conductance for DNA and RNA Sequence Identification.

Science.gov (United States)

Afsari, Sepideh; Korshoj, Lee E; Abel, Gary R; Khan, Sajida; Chatterjee, Anushree; Nagpal, Prashant

2017-11-28

Several nanoscale electronic methods have been proposed for high-throughput single-molecule nucleic acid sequence identification. While many studies display a large ensemble of measurements as "electronic fingerprints" with some promise for distinguishing the DNA and RNA nucleobases (adenine, guanine, cytosine, thymine, and uracil), important metrics such as accuracy and confidence of base calling fall well below the current genomic methods. Issues such as unreliable metal-molecule junction formation, variation of nucleotide conformations, insufficient differences between the molecular orbitals responsible for single-nucleotide conduction, and lack of rigorous base calling algorithms lead to overlapping nanoelectronic measurements and poor nucleotide discrimination, especially at low coverage on single molecules. Here, we demonstrate a technique for reproducible conductance measurements on conformation-constrained single nucleotides and an advanced algorithmic approach for distinguishing the nucleobases. Our quantum point contact single-nucleotide conductance sequencing (QPICS) method uses combed and electrostatically bound single DNA and RNA nucleotides on a self-assembled monolayer of cysteamine molecules. We demonstrate that by varying the applied bias and pH conditions, molecular conductance can be switched ON and OFF, leading to reversible nucleotide perturbation for electronic recognition (NPER). We utilize NPER as a method to achieve >99.7% accuracy for DNA and RNA base calling at low molecular coverage (∼12×) using unbiased single measurements on DNA/RNA nucleotides, which represents a significant advance compared to existing sequencing methods. These results demonstrate the potential for utilizing simple surface modifications and existing biochemical moieties in individual nucleobases for a reliable, direct, single-molecule, nanoelectronic DNA and RNA nucleotide identification method for sequencing.

DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

NARCIS (Netherlands)

Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it

Prediction of in-service time period of three differently stabilized single base propellants

Energy Technology Data Exchange (ETDEWEB)

Bohn, Manfred A. [Fraunhofer-Institut fuer Chemische Technologie (ICT), Pfinztal-Berghausen (Germany)

2009-06-15

Three nitrocellulose-based propellants for use in micro gas generators equipped with different stabilizing systems have been investigated to assess the stabilization capability with regard to in-service time, whereby strong time-temperature profiles have been applied. The three stabilizing systems have been (i) 0.74 mass-% diphenylamine (DPA) and 0.48 mass-% Akardite II (Ak II); (ii) 1.25 mass-% Ak II; (iii) 2.04 mass-% Ak II. Several profiles were considered. Two simulate the heating at sun exposure in hot areas, others consider environmental temperatures in hot-humid and hot-dry areas. They were evaluated according to the load and finally one was chosen for the assessment. The contents of stabilizers were determined by high performance liquid chromatography after Soxhlet type extraction. To describe stabilizer consumption, the most suitable kinetic model was taken. Therewith a prediction was made using the chosen time-temperature profile named 'Phoenix', designed for temperatures at the steering wheel. The objective was to reach with this profile 15 years until the consumption of primary stabilizer content. This is conservative, because with the stabilizing action of the consecutive products of the stabilizers longer times are possible. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

Summary and discussion of findings from: population dose and health impact of the accident at the Three Mile Island Nuclear Station (a preliminary assessment for the period March 28-April 7, 1979)

International Nuclear Information System (INIS)

Anon.

1979-01-01

This report was prepared by technical staff members of the Nuclear Regulatory Commission (NRC), the Department of Health, Education and Welfare (HEW), and the Environmental Protection Agency (EPA), who constitute an Ad Hoc Population Dose Assessment Group. It is an assessment of the health impact on the approximately 2 million offsite residents within 50 miles of the Three Mile Island Nuclear Station from the dose received by the entire population (collective dose). The Ad Hoc Group has examined in detail the available data for the period up to and including April 7, 1979. The report also addresses several areas of concern about the types of radionuclides released, about the contribution to population exposure due to beta radiation (which does not penetrate the clothing and skin) emitted from the released radionuclides, about the degree of coverage afforded by available radiation measurements, and about the range of health effects that may result from the estimated collective dose

Single Intramuscular-dose Toxicity of Water soluble Carthmi-Flos herbal acupuncture (WCF in Sprague-Dawley Rats

Directory of Open Access Journals (Sweden)

Lee Hyung-geol

2014-03-01

Full Text Available Objectives: This experiment was conducted to examine the toxicity of WCF (Water soluble Carthmi-Flos herbal acupuncture by administering a single intramuscular dose of WCF in 6-week-old, male and female Sprague-Dawley rats and to find the lethality dose for WCF. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices under a request by the Korean Pharmacopuncture Institute. This experiment was performed based on the testing standards of “Toxicity Test Standards for Drugs” by the Ministry of Food and Drug Safety. Subjects were divided into 4 groups: 1 control group in which normal saline was administered and 3 test groups in which 0.1, 0.5 or 1.0 mL of WCF was administered; a single intramuscular dose was injected into 5 males and 5 females in each group. General symptoms and body weights were observed/measured for 14 days after injection. At the end of the observation period, hematological and clinical chemistry tests were performed, followed by necropsy and histopathological examinations of the injected sections. Results: No mortalities were observed in any group. Also, symptoms, body weight, hematology, clinical chemistry and necropsy were not affected. However, histopathological examination of the injected part in one female in the 1.0-mL group showed infiltration of mononuclear cells and a multi-nucleated giant cell around eosinophilic material. Conclusion: Administration of single intramuscular doses of WCF in 3 groups of rats showed that the approximate lethal dose of WCF for all rats was in excess of 1.0 mL, as no mortalities were observed for injections up to and including 1.0 mL.

Multi-region and single-cell sequencing reveal variable genomic heterogeneity in rectal cancer.

Science.gov (United States)

Liu, Mingshan; Liu, Yang; Di, Jiabo; Su, Zhe; Yang, Hong; Jiang, Beihai; Wang, Zaozao; Zhuang, Meng; Bai, Fan; Su, Xiangqian

2017-11-23

Colorectal cancer is a heterogeneous group of malignancies with complex molecular subtypes. While colon cancer has been widely investigated, studies on rectal cancer are very limited. Here, we performed multi-region whole-exome sequencing and single-cell whole-genome sequencing to examine the genomic intratumor heterogeneity (ITH) of rectal tumors. We sequenced nine tumor regions and 88 single cells from two rectal cancer patients with tumors of the same molecular classification and characterized their mutation profiles and somatic copy number alterations (SCNAs) at the multi-region and the single-cell levels. A variable extent of genomic heterogeneity was observed between the two patients, and the degree of ITH increased when analyzed on the single-cell level. We found that major SCNAs were early events in cancer development and inherited steadily. Single-cell sequencing revealed mutations and SCNAs which were hidden in bulk sequencing. In summary, we studied the ITH of rectal cancer at regional and single-cell resolution and demonstrated that variable heterogeneity existed in two patients. The mutational scenarios and SCNA profiles of two patients with treatment naïve from the same molecular subtype are quite different. Our results suggest each tumor possesses its own architecture, which may result in different diagnosis, prognosis, and drug responses. Remarkable ITH exists in the two patients we have studied, providing a preliminary impression of ITH in rectal cancer.

Single-dose FTY720 pharmacokinetics, food effect, and pharmacological responses in healthy subjects

Science.gov (United States)

Kovarik, John M; Schmouder, Robert; Barilla, Denise; Wang, Yibin; Kraus, Gerolf

2004-01-01

Aims FTY720 is a sphingosine-1-phosphate receptor agonist that redirects lymphocytes from the circulation to lymph nodes without impairing lymphocyte function. It is being developed as an immunomodulator for the prevention of acute rejection after organ transplantation. This study was performed to provide guidance on administration with respect to meals and to measure pharmacologic responses in healthy subjects. Methods In this randomized, two-period, crossover study, 14 healthy subjects received placebo on day −1 of each period with baseline circadian measurements of lymphocyte count and heart rate. Subjects subsequently received a single 1 mg oral dose of FTY720 on day 1 under fasting conditions and after a high fat meal. Blood FTY720 concentrations, lymphocyte count, and supine heart rate were assessed over an 8 day period after each FTY720 dose. The effect of food on FTY720 pharmacokinetics was assessed by standard bioequivalence testing. Results Both the peak concentration (0.65 ± 0.17 vs 0.64 ± 0.18 ng ml−1) and total exposure (AUC 149 ± 65 vs 139 ± 43 ng ml−1 h) did not differ significantly between fasting and fed states, respectively. The corresponding fed/fasting ratios and 90% confidence intervals were 1.00 (0.86, 1.17) for Cmax and 0.98 (0.86, 1.11) for AUC. Under both treatment conditions peripheral blood lymphocyte count decreased from baseline by 38 ± 9% over the first 2 days postdose and then increased towards predose values over the subsequent week. Whereas a circadian rhythm in supine heart rate was preserved in the presence of FTY720, the heart rate vs time curve was shifted downwards by 10% over the first day postdose and then recovered to prestudy values by days 3–5 postdose. These changes were asymptomatic. Conclusions Single 1 mg doses of FTY720 were well tolerated in healthy subjects and elicited a moderate decrease in peripheral blood lymphocyte count and a transient decrease in heart rate consistent with its pharmacological

Bioequivalence of 250 mg lysine clonixinate tablets after a single oral dose in a healthy female Mexican population under fasting conditions.

Science.gov (United States)

Marcelín-Jiménez, G; Angeles, A C P; García, A; Morales, M; Rivera, L; Martín-Del-Campo, A

2010-05-01

To evaluate the bioequivalence between two 250 mg-tablets of lysine clonixinate, Dorixina Forte (Siegfried Rhein, México) as reference product, and Prestodol (Farmaceúticos Rayere, S.A., México) as test formulation. 26 healthy adult female Mexican volunteers received a single oral dose of 250-mg lysine clonixinate under fasting conditions. The drug was administered following a randomized, two-period, two-sequence, cross-over design. Twelve serial blood samples were collected up to 8 h after dosing, and clonixin (CLX) was measured by ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry. Decimal logarithm values of Cmax and area under the curve (AUC) were used to construct a classic confidence interval at 90% (90% CI). Bioequivalence was established if 90% CI of mean ratios (test/reference) fall within the 0.8-1.25 range. Volunteers formed a homogeneous population in terms of age (27.2 +/- 6.3 years), weight (55.9 +/- 6.5 kg), height (1.6 +/- 0.04 m), and body mass index (BMI) (22.91 +/- 2.03 kg/m(2)). Reference formulation exhibited the following pharmacokinetics: C(max) (32.39 +/- 8.32 microg/ml); t(max) (0.64 +/- 0.2 h); AUC0-8h (48.92 +/- 16.51 microg x h/ml); t1/2 (1.3 +/- 0.24 h); CLapp (5.64 +/- 1.99 l/h), and Vdapp (10.22 +/- 2.9 l). Concerning bioequivalence, 90% CI were: C(max) (82.32 - 98.79), AUC0-t (94.59-106.29), and AUC(0-inf) (94.61-106.42), with a statistical power of > 0.90 at every tested interval. This single-dose study found that both 250-mg immediate-release tablets of lysine clonixinate met the Mexican regulatory criteria for bioequivalence in these volunteers.

A new approach for solving capacitated lot sizing and scheduling problem with sequence and period-dependent setup costs

Directory of Open Access Journals (Sweden)

Imen Chaieb Memmi

2013-09-01

Full Text Available Purpose: We aim to examine the capacitated multi-item lot sizing problem which is a typical example of a large bucket model, where many different items can be produced on the same machine in one time period. We propose a new approach to determine the production sequence and lot sizes that minimize the sum of start up and setup costs, inventory and production costs over all periods.Design/methodology/approach: The approach is composed of three steps. First, we compute a lower bound on total cost. Then we propose a three sub-steps iteration procedure. We solve optimally the lot sizing problem without considering products sequencing and their cost. Then, we determine products quantities to produce each period while minimizing the storage and variable production costs. Given the products to manufacture each period, we determine its correspondent optimal products sequencing, by using a Branch and Bound algorithm. Given the sequences of products within each period, we evaluate the total start up and setup cost. We compare then the total cost obtained to the lower bound of the total cost. If this value riches a prefixed value, we stop. Otherwise, we modify the results of lot sizing problem.Findings and Originality/value: We show using an illustrative example, that the difference between the total cost and its lower bound is only 10%. This gap depends on the significance of the inventory and production costs and the machine’s capacity. Comparing the approach we develop with a traditional one, we show that we manage to reduce the total cost by 30%.Research limitations/implications: Our model fits better to real-world situations where production systems run continuously. This model is applied for limited number of part types and periods.Practical implications: Our approach determines the products to manufacture each time period, their economic amounts, and their scheduling within each period. This outcome should help decision makers bearing expensive

Gamma radiation-induced Impairment of hippocampal neurogenesis, comparison of single and fractionated dose regimens

International Nuclear Information System (INIS)

Khoshbin khoshnazar, A. R; Jahanshahi, M; Azami, N. S

2012-01-01

Radiation therapy of the brain is associated with many consequences, including cognitive disorders. Pathogenesis of radiation induced cognitive disorder is not clear, but reduction of neurogenesis in hippocampus may be an underlying reason. 24 adult male rats entered to study. Radiation absorbed dose to midbrain was 10 Gy, delivered by routine cobalt radiotherapy machine which its output was measured 115.24 cGy/min. The rats were divided in four groups of sixes, including groups of control, single fraction 10 Gy, fractionated 10 Gy and finally anaesthesia sham group. Number of pyramidal nerve cells was counted in two regions of hippocampus formation (CA1 and CA3). The radiation could reduce the number of cells in two regions of hippocampus significantly (p=0.000). It seems fractionated 10 Gy irradiation to more efficient than single fraction, while role of anaesthesia drug should be cautiously assessed. Moreover the rate of neurogenesis reduction was determined the same in these regions of hippocampus meaning the same radiosensitivity of cells

Lower bounds on the periodic Hamming correlations of frequency hopping sequences with low hit zone

Institute of Scientific and Technical Information of China (English)

无

2006-01-01

In this paper, several periodic Hamming correlation lower bounds for frequency hopping sequences with low hit zone, with respect to the size p of the frequency slot set, the sequence length L, the family size M, low hit zone LH ( or no hit zone NH ), the maximum periodic Hamming autocorrelation sidelobe Ha and the maximum periodic Hamming crosscorrelation Hc, are established. It is shown that the new bounds include the known Lempel-Greenberger bounds, T.S. Seay bounds and Peng-Fan bounds for the conventional frequency hopping sequences as special cases.

GapMis: a tool for pairwise sequence alignment with a single gap.

Science.gov (United States)

Flouri, Tomás; Frousios, Kimon; Iliopoulos, Costas S; Park, Kunsoo; Pissis, Solon P; Tischler, German

2013-08-01

Pairwise sequence alignment has received a new motivation due to the advent of recent patents in next-generation sequencing technologies, particularly so for the application of re-sequencing---the assembly of a genome directed by a reference sequence. After the fast alignment between a factor of the reference sequence and a high-quality fragment of a short read by a short-read alignment programme, an important problem is to find the alignment between a relatively short succeeding factor of the reference sequence and the remaining low-quality part of the read allowing a number of mismatches and the insertion of a single gap in the alignment. We present GapMis, a tool for pairwise sequence alignment with a single gap. It is based on a simple algorithm, which computes a different version of the traditional dynamic programming matrix. The presented experimental results demonstrate that GapMis is more suitable and efficient than most popular tools for this task.

Draft genomic sequencing of six potential extraintestinal pathogenic Escherichia coli isolates from retail chicken meat.

Science.gov (United States)

Potential Extraintestinal pathogenic Escherichia coli isolates DP254, WH333, WH398, F356, FEX675 and FEX725 were isolated from retail chicken meat products. Here, we report the draft genome sequences for these six E. coli isolates, which are currently being used in food safety research....

Value of MR cisternography using three-dimensional half-fourier single-shot fast spin-echo sequences in the diagnosis of diseases related to cranial nerves VII and VIII

Energy Technology Data Exchange (ETDEWEB)

Yamakami, Norio [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

1999-05-01

The purpose of this study was to evaluate the value of MR cisternography using three-dimensional half-Fourier single-shot fast spin-echo sequences in the diagnosis of diseasea related to cranial nerves VII and VIII. With a 0.5-T imager, the most appropriate setting of echo time and section thickness was first assessed in five volunteers. This resulted in echo time of 250 msec and section thickness of 2 mm as the most effective parameters. Second, using echo time of 120 msec and section thickness of 1.5 mm that were available from the beginning of this study, the demonstration of four nerves within the audistory canal was assessed in seven volunteers. In all of the volunteers, the facial, cochlear, and vestibular nerves were determined with demonstration of each of superior and inferior vestibular nerves in four of them. Next, MR cisternography using the same echo time and section thickness was applied in 368 patients with suspicion of acoustic neurinoma and 14 with hemifacial spasm. In 28 of the 368 patients, MR cisternograms depicted an acoustic neurinoma that was confirmed on postcontrast T1-weighted images. Meanwhile, in five of the 14 patients with hemifacial spasm, MR cisternograms revealed a vessel compressing the root exit zone of the affected facial nerve. It is concluded that MR cisternography using three-dimensional half-Fourier single-shot fast spin-echo sequences can be a useful means for demonstrating nerves within the auditory nerve as well as for the screening of acoustic neurionoma. (author)

Value of MR cisternography using three-dimensional half-fourier single-shot fast spin-echo sequences in the diagnosis of diseases related to cranial nerves VII and VIII

International Nuclear Information System (INIS)

Yamakami, Norio

1999-01-01

The purpose of this study was to evaluate the value of MR cisternography using three-dimensional half-Fourier single-shot fast spin-echo sequences in the diagnosis of diseasea related to cranial nerves VII and VIII. With a 0.5-T imager, the most appropriate setting of echo time and section thickness was first assessed in five volunteers. This resulted in echo time of 250 msec and section thickness of 2 mm as the most effective parameters. Second, using echo time of 120 msec and section thickness of 1.5 mm that were available from the beginning of this study, the demonstration of four nerves within the audistory canal was assessed in seven volunteers. In all of the volunteers, the facial, cochlear, and vestibular nerves were determined with demonstration of each of superior and inferior vestibular nerves in four of them. Next, MR cisternography using the same echo time and section thickness was applied in 368 patients with suspicion of acoustic neurinoma and 14 with hemifacial spasm. In 28 of the 368 patients, MR cisternograms depicted an acoustic neurinoma that was confirmed on postcontrast T1-weighted images. Meanwhile, in five of the 14 patients with hemifacial spasm, MR cisternograms revealed a vessel compressing the root exit zone of the affected facial nerve. It is concluded that MR cisternography using three-dimensional half-Fourier single-shot fast spin-echo sequences can be a useful means for demonstrating nerves within the auditory nerve as well as for the screening of acoustic neurionoma. (author)

Dose optimisation in single plane interstitial brachytherapy

DEFF Research Database (Denmark)

Tanderup, Kari; Hellebust, Taran Paulsen; Honoré, Henriette Benedicte

2006-01-01

patients,       treated for recurrent rectal and cervical cancer, flexible catheters were       sutured intra-operatively to the tumour bed in areas with compromised       surgical margin. Both non-optimised, geometrically and graphically       optimised CT -based dose plans were made. The overdose index...... on the       regularity of the implant, such that the benefit of optimisation was       larger for irregular implants. OI and HI correlated strongly with target       volume limiting the usability of these parameters for comparison of dose       plans between patients. CONCLUSIONS: Dwell time optimisation significantly......BACKGROUND AND PURPOSE: Brachytherapy dose distributions can be optimised       by modulation of source dwell times. In this study dose optimisation in       single planar interstitial implants was evaluated in order to quantify the       potential benefit in patients. MATERIAL AND METHODS: In 14...

Six switches solution for single-phase AC/DC/AC converter with capability of second-order power mitigation in DC-link capacitor

DEFF Research Database (Denmark)

Liu, Xiong; Wang, Peng; Loh, Poh Chiang

2011-01-01

This paper proposes an approach for DC-link second-order harmonic power cancellation in single-phase AC/DC/AC converter with reduced number of switches. The proposed six-switch converter has two bridges with three switches in each of them, where the middle switch in each bridge is shared by the A...

Frequency of wound infection in non-perforated appendicitis with use of single dose perforative antibiotics

International Nuclear Information System (INIS)

Ali, K.; Latif, H.; Ahmad, S.

2015-01-01

Antibiotics are used both pre and post-operatively in acute appendicitis for preventing wound infection. It has been observed that the routine use of post-operative antibiotics is not necessary in cases of non-perforated appendicitis as only prophylactic antibiotics are sufficient to prevent wound infection. The aim of this study was to see the frequency of wound infection in non-perforated appendicitis with single dose preoperative antibiotics only. Method: This observational study was conducted at the Department of Surgery, Ayub Medical College, Abbottabad from May to November 2014. A total of 121 patients with non-perforated appendicitis were included in the study. Only single dose preoperative antibiotics were used. The patients were followed for wound infection till 8th post-operative day. Results: 121 patients, 56(46.28%) male and 65(53.72%) female were included in the study. The mean age of patients was 27.41 ± 7.12 years with an age range of 18 to 45 years. In the entire series, 7(5.78%) patients developed wound infection. The infection was minor which settled with conservative therapy. Prophylactic antibiotics were found efficacious in 114(94.21%) patients. There was no significant association between wound infection and age and gender. Conclusion: Single dose preoperative antibiotics were found effective in controlling post-operative wound infection without the need of extending the antibiotics to post-operative period in cases of non-perforated appendicitis. (author)

Direct chromosome-length haplotyping by single-cell sequencing

NARCIS (Netherlands)

Porubský, David; Sanders, Ashley D; van Wietmarschen, Niek; Falconer, Ester; Hills, Mark; Spierings, Diana C J; Bevova, Marianna R; Guryev, Victor; Lansdorp, Peter Michael

Haplotypes are fundamental to fully characterize the diploid genome of an individual, yet methods to directly chart the unique genetic makeup of each parental chromosome are lacking. Here we introduce single-cell DNA template strand sequencing (Strand-seq) as a novel approach to phasing diploid

[Contrastive analysis of artifacts produced by metal dental crowns in 3.0 T magnetic resonance imaging with six sequences].

Science.gov (United States)

Lan, Gao; Yunmin, Lian; Pu, Wang; Haili, Huai

2016-06-01

This study aimed to observe and evaluate six 3.0 T sequences of metallic artifacts produced by metal dental crowns. Dental crowns fabricated with four different materials (Co-Gr, Ni-Gr, Ti alloy and pure Ti) were evaluated. A mature crossbreed dog was used as the experimental animal, and crowns were fabricated for its upper right second premolar. Each crown was examined through head MRI (3.0 T) with six sequences, namely, T₁ weighted-imaging of spin echo (T₁W/SE), T₂ weighted-imaging of inversion recovery (T₂W/IR), T₂ star gradient echo (T₂*/GRE), T2 weighted-imaging of fast spin echo (T₂W/FSE), T₁ weighted-imaging of fluid attenuate inversion recovery (T₂W/FLAIR), and T₂ weighted-imaging of propeller (T₂W/PROP). The largest area and layers of artifacts were assessed and compared. The artifact in the T₂*/GRE sequence was significantly wider than those in the other sequences (P 0.05). T₂*/GRE exhibit the strongest influence on the artifact, whereas the five other sequences contribute equally to artifact generation.

Infantile fibrosarcoma: Magnetic resonance imaging findings in six cases

Energy Technology Data Exchange (ETDEWEB)

Canale, Sandra [Department of Radiology, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif (France)], E-mail: canalesandra@yahoo.com; Vanel, Daniel [Department of Radiology, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif (France); Istituti Ortopedici Rizzoli, 1/10 via di Barbiano, 40136 Bologna (Italy); Couanet, Dominique [Department of Radiology, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif (France); Patte, Catherine [Department of Pediatrics, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif (France); Caramella, Caroline; Dromain, Clarisse [Department of Radiology, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif (France)

2009-10-15

Purpose: To retrospectively review magnetic resonance (MR) imaging features in a series of six infantile fibrosarcomas to find out if MR can suggest this unusual diagnosis and to highlight the value of MR during and following treatment. Materials and methods: The records of six cases of histologically proven infantile fibrosarcoma were retrieved from the files of our cancer center. All imaging data available were consensually reviewed by two radiologists. Results: There were five females and one male (age range at diagnosis, 0-12 months; mean, 6 months). The most common finding was a well-circumscribed single mass in five patients (83%). All tumors had arisen on limbs; at their proximal or distal extremity or at the root of the limb. The masses were 9 cm large in mean diameter. The initial tumor signal was isointense to muscle on T1-weighted and hyperintense on T2-weighted sequences. All masses were well circumscribed and half of them contained internal fibrous septa. The internal signal was homogeneous in three patients and heterogeneous in the three others. An intense enhancement was seen in all three contrast-enhanced exams available; heterogeneous in two cases and homogeneous in one. Osseous erosion was observed in only one patient who was the only one with distant metastasis. After treatment (chemotherapy and very limited surgery), tumors had totally disappeared, leaving muscle fat infiltration in two patients and subcutaneous fat hypertrophy in one patient. Conclusion: Although imaging findings are not specific of infantile fibrosarcoma, this diagnosis could be suggested when MR imaging depicts a large well-circumscribed mass arising in a limb at birth or during the neonatal period. This mass is sometimes heterogeneous and septate and exhibits an isointense T1- and hyperintense T2-weighted signals and strong enhancement. MR is also the technique of choice for follow-up during treatment which consists nowadays almost exclusively in chemotherapy.

Effective dose to staff from interventional procedures: Estimations from single and double dosimetry

International Nuclear Information System (INIS)

Kuipers, G.; Velders, X. L.

2009-01-01

The exposure of 11 physicians performing interventional procedures was measured by means of two personal dosemeters. One personal dosemeter was worn outside the lead apron and an additional under the lead apron. The study was set up in order to determine the added value of a dosemeter worn under the lead apron. With the doses measured, the effective doses of the physicians were estimated using an algorithm for single dosimetry and two algorithms for double dosimetry. The effective doses calculated with the single dosimetry algorithm ranged from 0.11 to 0.85 mSv in 4 weeks. With the double dosimetry algorithms, the effective doses ranged from 0.02 mSv to 0.47 mSv. The statistical analysis revealed no significant differences in the accuracy of the effective doses calculated with single or double dosimetry algorithms. It was concluded that the effective dose cannot be considered a more accurate estimate when two dosemeters are used instead of one. (authors)

Dose rate effect from the relationship between ICRU rectal dose and local control rate in intracavitary radiotherapy for carcinoma of the uterine cervix. Six fraction HDR and three-fraction LDR in three weeks

International Nuclear Information System (INIS)

Jingu, Kenichi; Akita, Yuzou; Ohmagari, Jyunichi

2001-01-01

The dose rate effect, low dose rate radiotherapy (LDR)/high dose rate radiotherapy (HDR), was calculated using the isoeffect ICRU rectal dose by intracavitary radiotherapy (ICRT) for uterine cervix cancer. The subjects analyzed consisted of 78 LDR and 74 HDR patients whose ICRU rectal dose could be calculated and whose local control as stage II/III cases could be evaluated. The point A dose in ICRT was 45-55 Gy/3 fractions/3 weeks for LDR and 30 Gy/6 fractions/3 weeks for HDR. The dose effect relationships associated with local control at each whole pelvis external radiation dose were calculated using the double integration method and Probit analysis, and the 50% and 90% local control ICRU rectal doses were calculated from this relationship. Finally, the dose rate effect LDR/HDR was determined from 50% and 90% local control doses. The dose rate effect calculated from the 50% local control dose was 1.24 and that from the 90% local control dose was 1.14. (author)

Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy

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Feras Sendy

2015-01-01

Full Text Available Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67% received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225 of the patients. 28% (63/225 were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63 of failure received a second dose of methotrexate, and 37% (23/63 underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

Failure rate of single dose methotrexate in managment of ectopic pregnancy.

Science.gov (United States)

Sendy, Feras; AlShehri, Eman; AlAjmi, Amani; Bamanie, Elham; Appani, Surekha; Shams, Taghreed

2015-01-01

Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67%)) received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225) of the patients. 28% (63/225) were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63) of failure received a second dose of methotrexate, and 37% (23/63) underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

Correlation between the single, high dose of ingested baclofen and clinical symptoms

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Jacek Sein Anand

2017-12-01

There is a statistically significant correlation between the dose of ingested baclofen and the presence of acute respiratory failure, and duration of mechanical ventilation. Patients who have taken a single dose of baclofen of 200 mg, or higher, should be managed in centres able to provide continuous monitoring of life functions. Those with a higher level of a single dose of baclofen ingestion (>500 mg, should be hospitalized in a Toxicology Unit or Intensive Care Unit able to provide airway support and mechanical ventilation.

Favorable Preliminary Outcomes for Men With Low- and Intermediate-risk Prostate Cancer Treated With 19-Gy Single-fraction High-dose-rate Brachytherapy

Energy Technology Data Exchange (ETDEWEB)

Krauss, Daniel J., E-mail: dkrauss@beaumont.edu [Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States); Ye, Hong [Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States); Martinez, Alvaro A. [21st Century Oncology, Farmington Hills, Michigan (United States); Mitchell, Beth; Sebastian, Evelyn; Limbacher, Amy; Gustafson, Gary S. [Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States)

2017-01-01

Purpose: To report the toxicity and preliminary clinical outcomes of a prospective trial evaluating 19-Gy, single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. Methods and Materials: A total of 63 patients were treated according to an institutional review board-approved prospective study of single-fraction HDR brachytherapy. Eligible patients had tumor stage ≤T2a, prostate-specific antigen level ≤15 ng/mL, and Gleason score ≤7. Patients with a prostate gland volume >50 cm{sup 3} and baseline American Urologic Association symptom score >12 were ineligible. Patients underwent transrectal ultrasound-guided transperineal implantation of the prostate, followed by single-fraction HDR brachytherapy. Treatment was delivered using {sup 192}Ir to a dose of 19 Gy prescribed to the prostate, with no additional margin applied. Results: Of the 63 patients, 58 had data available for analysis. Five patients had withdrawn consent during the follow-up period. The median follow-up period was 2.9 years (range 0.3-5.2). The median age was 61.4 years. The median gland volume at treatment was 34.8 cm{sup 3}. Of the 58 patients, 91% had T1 disease, 71% had Gleason score ≤6 (29% with Gleason score 7), and the median pretreatment prostate-specific antigen level was 5.1 ng/mL. The acute and chronic grade 2 genitourinary toxicity incidence was 12.1% and 10.3%, respectively. No grade 3 urinary toxicity occurred. No patients experienced acute rectal toxicity grade ≥2, and 2 experienced grade ≥2 chronic gastrointestinal toxicity. Three patients experienced biochemical failure, yielding a 3-year cumulative incidence estimate of 6.8%. Conclusions: Single-fraction HDR brachytherapy is well-tolerated, with favorable preliminary biochemical and clinical disease control rates.

Three-dimensional dose-response models of risk for radiation injury carcinogenesis

International Nuclear Information System (INIS)

Raabe, O.G.

1988-01-01

The use of computer graphics in conjunction with three-dimensional models of dose-response relationships for chronic exposure to ionizing radiation dramaticly clarifies the separate and interactive roles of competing risks. The three dimensions are average dose rate, exposure time, and risk. As an example, the functionally injurious and carcinogenic responses after systemic uptake of Ra-226 by beagles, mice and people with consequent alpha particle irradiation of the bone are represented by three-dimensional dose-rate/time/response surfaces that demonstrate the contributions with the passage of time of the competing deleterious responses. These relationships are further evaluated by mathematical stripping with three-dimensional illustrations that graphically show the resultant separate contribution of each effect. Radiation bone injury predominates at high dose rates and bone cancer at intermediate dose rates. Low dose rates result in spontaneous deaths from natural aging, yielding a type of practical threshold for bone cancer induction. Risk assessment is benefited by the insights that become apparent with these three-dimensional models. The improved conceptualization afforded by them contributes to planning and evaluating epidemiological analyses and experimental studies

Efficacy of Single-dose and 2-dose Intravenous Administration of Ramosetron in Preventing Postoperative Nausea and Vomiting After Laparoscopic Gynecologic Operation: A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial.

Science.gov (United States)

Lee, Banghyun; Kim, Kidong; Suh, Dong Hoon; Shin, Hyun-Jung; No, Jae Hong; Lee, Jung Ryeol; Jee, Byung Chul; Hwang, Jung Won; Do, Sang Hwan; Kim, Yong Beom

2017-06-01

This randomized trial investigated whether a 2-dose administration of intravenous ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective than a single-dose administration in preventing postoperative nausea and vomiting (PONV) in 89 patients who were scheduled to undergo laparoscopic operation for benign gynecologic diseases and to receive intravenous patient-controlled analgesia for relief of postoperative pain. After assignment at a ratio of 1:1, intravenous ramosetron (0.3 mg) was initially administered at the end of skin closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were administered to the study and control groups, respectively, at 4 hours after the operation. The baseline and operative characteristics were similar between the groups. The incidence of PONV during the 24-hour period after operation which was assessed as the primary endpoint did not differ between the groups. No serious adverse events occurred in either group. A 2-dose administration of intravenous ramosetron may not be superior to a single-dose administration in preventing PONV in patients undergoing laparoscopic operation for benign gynecologic diseases.

Power sharing algorithm for vector controlled six-phase AC motor with four customary three-phase voltage source inverter drive

Directory of Open Access Journals (Sweden)

Sanjeevikumar Padmanaban

2015-09-01

Full Text Available This paper considered a six-phase (asymmetrical induction motor, kept 30° phase displacement between two set of three-phase open-end stator windings configuration. The drive system consists of four classical three-phase voltage inverters (VSIs and all four dc sources are deliberately kept isolated. Therefore, zero-sequence/homopolar current components cannot flow. The original and effective power sharing algorithm is proposed in this paper with three variables (degree of freedom based on synchronous field oriented control (FOC. A standard three-level space vector pulse width modulation (SVPWM by nearest three vectors (NTVs approach is adopted to regulate each couple of VSIs. The proposed power sharing algorithm is verified by complete numerical simulation modeling (Matlab/Simulink-PLECS software of whole ac drive system by observing the dynamic behaviors in different designed condition. Set of results are provided in this paper, which confirms a good agreement with theoretical development.

Efficiency of early, single-dose probiotic administration methods on performance, small intestinal morphology, blood biochemistry, and immune response of Japanese quail.

Science.gov (United States)

Seifi, Kazem; Karimi Torshizi, Mohammad Amir; Rahimi, Shaban; Kazemifard, Mohammad

2017-07-01

The aim of the present study was to investigate the efficacy of early probiotics (single dose) administered in different ways, on quails' performance, small intestine morphology, blood biochemistry, and immune response. In total, 192 day-old chicks were used in one of the following experimental groups before being transferred to a raising room: 1) Control (no probiotic administered), 2) oral gavage, 3) spray, and 4) vent lip. Four replicates of 12 chicks per cage were considered for each treatment and birds were raised up to 35 d in the same conditions. Probiotic treated birds had higher d 1 to 35 feed intake than the control group (P birds had a higher body weight gain as compared to the control (P birds compared to control (P  0.01). None of the immune-related parameters were affected by the probiotic (P > 0.05). Single dose usage of probiotics exerts its beneficial effects on quails' body weight gain, feed intake and mortality in 1 to 35 d period, regardless of the route of administration. This work generally supports the efficacy of single-dose usage of probiotics and suggests the spray of probiotics as an early, single-dose administration method. © 2017 Poultry Science Association Inc.

Radioprotective effects in mice by a single dose of subcutaneous administration of cobaltous chloride post γ-rays irradiation with a sublethal dose

International Nuclear Information System (INIS)

Izumo, Yoshiro; Ogata, Hiromitsu

1993-01-01

Radioprotective effects were investigated in mice which received subcutaneously a single dose of each inorganic metal: Co, Cu, Rb, Sr, Mo and W 24 hours post irradiation of 60 Co γ-rays with a sublethal dose. The effects were observed in mice injected with Co at an optimum dosage of 20 mg/kg·body weight. Then to elucidate mechanisms of the effects, mice were injected with Co containing the radioactive tracer ( 60 Co) following the radiation exposure, measured elimination of the radioactivity for 7 days, then sacrificed and divided to some tissues and organs. The radioactivity in whole body during this period resulted in a markedly higher retention than that for mice injected with [ 60 Co] alone, as well as liver in the organs. These higher retentions appeared to be related to the radioprotective effects. (author)

Protect Patients by Using Single- and Multi-Dose Vials Correctly

Centers for Disease Control (CDC) Podcasts

2014-07-10

CDC’s One & Only Campaign urges healthcare providers to recognize the differences between single-dose and multi-dose vials, and to understand appropriate use of each container type.  Created: 7/10/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 7/10/2014.

A periodic-type dose effect of insulin in the blood glucose level of a ...

African Journals Online (AJOL)

We investigated in this paper the effect of a periodic-type insulin dose on a diabetic patient. An appropriate matching condition is introduced in our problem by expressing the insulin dose using a Fourier series expansion. Our result gives insight to the state of the patient over a period of administration. Clearly, there is the ...

Single-dose safety and pharmacokinetic evaluation of fluorocoxib A: pilot study of novel cyclooxygenase-2-targeted optical imaging agent in a canine model

Science.gov (United States)

Cekanova, Maria; Uddin, Md. Jashim; Legendre, Alfred M.; Galyon, Gina; Bartges, Joseph W.; Callens, Amanda; Martin-Jimenez, Tomas; Marnett, Lawrence J.

2012-11-01

We evaluated preclinical single-dose safety, pharmacokinetic properties, and specific uptake of the new optical imaging agent fluorocoxib A in dogs. Fluorocoxib A, N-[(5-carboxy-X-rhodaminyl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, selectively binds and inhibits the cyclooxygenase-2 (COX-2) enzyme, which is overexpressed in many cancers. Safety pilot studies were performed in research dogs following intravenous (i.v.) administration of 0.1 and 1 mg/kg fluorocoxib A. Blood and urine samples collected three days after administration of each dose of fluorocoxib A revealed no evidence of toxicity, and no clinically relevant adverse events were noted on physical examination of exposed dogs over that time period. Pharmacokinetic parameters were assessed in additional research dogs from plasma collected at several time points after i.v. administration of fluorocoxib A using high-performance liquid chromatography analysis. The pharmacokinetic studies using 1 mg/kg showed a peak of fluorocoxib A (92±28 ng/ml) in plasma collected at 0.5 h. Tumor specific uptake of fluorocoxib A was demonstrated using a dog diagnosed with colorectal cancer expressing COX-2. Our data support the safe single-dose administration and in vivo efficacy of fluorocoxib A, suggesting a high potential for successful translation to clinical use as an imaging agent for improved tumor detection in humans.

Serum level modifications of female sex hormones after radiocastration with different total doses

International Nuclear Information System (INIS)

Naujokat, B.; Rohloff, R.; Willich, N.; Eiermann, W.

1988-01-01

We determined serum level of estradiol, FSH and LH over a period of six to eight weeks after ovarian irradiation for castration with different doses (2x2.5 Gy/3x2.5 Gy/4x2.5 Gy) in 15 patients with metastatic breast cancer as compared to changes after ovarectomy in five patients. The time course of the changing estradiol-, FSH and LH-serum levels sigificantly depends on the ovarian dose. After radiological castration with a dose of 4x2.5 Gy = 10 Gy in four days the estrogen levels decrease within two to three weeks, and the FSH- and LH-levels increase after three to four weeks into the postmenopausal range. Therefore, the time course is not very different from changes after ovarectomy. (orig.) [de

A new HCV genotype 6 subtype designated 6v was confirmed with three complete genome sequences.

Science.gov (United States)

Wang, Yizhong; Xia, Xueshan; Li, Chunhua; Maneekarn, Niwat; Xia, Wenjie; Zhao, Wenhua; Feng, Yue; Kung, Hsiang Fu; Fu, Yongshui; Lu, Ling

2009-03-01

Although hepatitis C virus (HCV) genotype 6 is classified into 21 subtypes, 6a-6u, new variants continue to be identified. To characterize the full-length genomes of three novel HCV genotype 6 variants: KMN02, KM046 and KM181. From sera of patients with HCV infection, the entire HCV genome was amplified by RT-PCR followed by direct DNA sequencing and phylogenetic analysis. The sera contained HCV genomes of 9461, 9429, and 9461nt in length, and each harboured a single ORF of 9051nt. The genomes showed 95.3-98.1% nucleotide similarity to each other and 72.2-75.4% similarity to 23 genotype 6 reference sequences, which represent subtypes 6a-6u and unassigned variants km41 and gz52557. Phylogenetic analyses demonstrated that they were genotype 6, but were subtypically distinct. Based on the current criteria of HCV classification, they were designed to represent a new subtype, 6v. Analysis of E1 and NS5B region partial sequences revealed two additional related variants, CMBD-14 and CMBD-86 that had been previously reported in northern Thailand and sequences dropped into Genbank. Three novel HCV genotype 6 variants were entirely sequenced and designated subtype 6v.

Sequencing genes in silico using single nucleotide polymorphisms

Directory of Open Access Journals (Sweden)

Zhang Xinyi

2012-01-01

Full Text Available Abstract Background The advent of high throughput sequencing technology has enabled the 1000 Genomes Project Pilot 3 to generate complete sequence data for more than 906 genes and 8,140 exons representing 697 subjects. The 1000 Genomes database provides a critical opportunity for further interpreting disease associations with single nucleotide polymorphisms (SNPs discovered from genetic association studies. Currently, direct sequencing of candidate genes or regions on a large number of subjects remains both cost- and time-prohibitive. Results To accelerate the translation from discovery to functional studies, we propose an in silico gene sequencing method (ISS, which predicts phased sequences of intragenic regions, using SNPs. The key underlying idea of our method is to infer diploid sequences (a pair of phased sequences/alleles at every functional locus utilizing the deep sequencing data from the 1000 Genomes Project and SNP data from the HapMap Project, and to build prediction models using flanking SNPs. Using this method, we have developed a database of prediction models for 611 known genes. Sequence prediction accuracy for these genes is 96.26% on average (ranges 79%-100%. This database of prediction models can be enhanced and scaled up to include new genes as the 1000 Genomes Project sequences additional genes on additional individuals. Applying our predictive model for the KCNJ11 gene to the Wellcome Trust Case Control Consortium (WTCCC Type 2 diabetes cohort, we demonstrate how the prediction of phased sequences inferred from GWAS SNP genotype data can be used to facilitate interpretation and identify a probable functional mechanism such as protein changes. Conclusions Prior to the general availability of routine sequencing of all subjects, the ISS method proposed here provides a time- and cost-effective approach to broadening the characterization of disease associated SNPs and regions, and facilitating the prioritization of candidate

An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain.

Science.gov (United States)

Nalamachu, Srinivas

2013-12-01

Breakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients. This was a single-center, non-randomized, open-label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 μg sublingual fentanyl tablet (Abstral(®), Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel. Disintegration time (mean ± SD) for sublingual fentanyl tablets (all doses) was 88.2 ± 55.1 s. Mean disintegration times tended to be slightly longer for the 200 μg (96.7 ± 57.9 s) and 300 μg doses (98.6 ± 64.8 s) compared to the 100 μg dose (69.5 ± 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age. Sublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve.

Transversus Abdominis Plane Blocks with Single-Dose Liposomal Bupivacaine in Conjunction with a Nonnarcotic Pain Regimen Help Reduce Length of Stay following Abdominally Based Microsurgical Breast Reconstruction.

Science.gov (United States)

Jablonka, Eric M; Lamelas, Andreas M; Kim, Julie N; Molina, Bianca; Molina, Nathan; Okwali, Michelle; Samson, William; Sultan, Mark R; Dayan, Joseph H; Smith, Mark L

2017-08-01

Side effects associated with use of postoperative narcotics for pain control can delay recovery after abdominally based microsurgical breast reconstruction. The authors evaluated a nonnarcotic pain control regimen in conjunction with bilateral transversus abdominis plane blocks on facilitating early hospital discharge. A retrospective analysis was performed of consecutive patients who underwent breast reconstruction using abdominally based free flaps, with or without being included in a nonnarcotic protocol using intraoperative transversus abdominis plane blockade. During this period, the use of locoregional analgesia evolved from none (control), to continuous bupivacaine infusion transversus abdominis plane and catheters, to single-dose transversus abdominis plane blockade with liposomal bupivacaine solution. Demographic factors, length of stay, inpatient opioid consumption, and complications were reported for all three groups. One hundred twenty-eight consecutive patients (182 flaps) were identified. Forty patients (62 flaps) were in the infusion-liposomal bupivacaine group, 48 (66 flaps) were in the single-dose blockade-catheter group, and 40 (54 flaps) were in the control group. The infusion-liposomal bupivacaine patients had a significantly shorter hospital stay compared with the single-dose blockade-catheter group (2.65 ± 0.66 versus 3.52 ± 0.92 days; p plane blocks performed with single injections of liposomal bupivacaine help facilitate early hospital discharge after abdominally based microsurgical breast reconstruction. A trend toward consistent discharge by postoperative day 2 was seen. This could result in significant cost savings for health care systems. Therapeutic, III.

Efficacy and tolerability of treatment with single doses of diethylcarbamazine (DEC) and DEC plus albendazole (ABZ) for three consecutive years in lymphatic filariasis: a field study in India.

Science.gov (United States)

Kshirsagar, Nilima A; Gogtay, N J; Garg, B S; Deshmukh, P R; Rajgor, D D; Kadam, V S; Thakur, P A; Gupta, A; Ingole, N S; Lazdins-Helds, J K

2017-10-01

Lymphatic filariasis (LF) affects 73 countries, causes morbidity and impedes socioeconomic development. We had found no difference in safety and micro (Mf) and macro filarial action of single-dose diethylcarbamazine (DEC) and DEC + albendazole (ABZ) in an F01 study done in India (year 2000). There was a programmatic need to evaluate safety and efficacy of multiple annual treatments (F02). Subjects (155) from the F01 study, meeting inclusion-exclusion criteria, were enrolled in F02 and treated with further two annual doses of DEC or DEC + ABZ. Efficacy was evaluated for Mf positivity by peripheral smear (PS) and nucleopore (NP) filter, circulating filarial antigen (CFA) and filarial dance sign (FDS) positivity and Mf count at yearly follow-up. Safety was assessed for 5 days after drug administration. Total of 139 subjects evaluated for efficacy (69 DEC and 70 DEC + ABZ group). Mf positivity prevalence declined progressively by 95% (PS), 66% (NP), and 95% (PS) and 86% (NP); CFA positivity prevalence declined by 15% and 9%; FDS by 100% each; Mf count declined by 75.5 and 76.9% with three annual treatment of DEC and DEC + ABZ, respectively. Addition of ABZ did not show any advantage over DEC given as three annual rounds for LF. DEC and DEC + ABZ were well tolerated. There was no correlation between result of CFA and FDS, (both claimed to be indicative of adult worm). Analysis of published studies and our data indicate that macrofilaricidal effect of DEC/DEC + ABZ may be seen in children and not adults, with three or more annual dosing.

Comparison of scatter doses from a multislice and a single slice CT scanner

International Nuclear Information System (INIS)

Burrage, J. W.; Causer, D. A.

2006-01-01

During shielding calculations for a new multislice CT (MSCT) scanner it was found that the manufacturer's data indicated significantly higher external scatter doses than would be generated for a single slice CT (SSCT). Even allowing for increased beam width, the manufacturer's data indicated that the scatter dose per scan was higher by a factor of about 3 to 4. The magnitude of the discrepancy was contrary to expectations and also contrary to a statement by the UK ImPACT group, which indicated that when beam width is taken into account, the scatter doses should be similar. The matter was investigated by comparing scatter doses from an SSCT and an MSCT. Scatter measurements were performed at three points using a standard perspex CTDI phantom, and CT dose indices were also measured to compare scanner output. MSCT measurements were performed with a 40 mm wide beam, SSCT measurements with a 10 mm wide beam. A film badge survey was also performed after the installation of the MSCT scanner to assess the adequacy of lead shielding in the room. It was found that the scatter doses from the MSCT were lower than indicated by the manufacturer's data. MSCT scatter doses were approximately 4 times higher than those from the SSCT, consistent with expectations due to beam width differences. The CT dose indices were similar, and the film badge survey indicated that the existing shielding, which had been adequate for the SSCT, was also adequate for the MSCT

Superconducting six-axis accelerometer

Science.gov (United States)

Paik, H. J.

1990-01-01

A new superconducting accelerometer, capable of measuring both linear and angular accelerations, is under development at the University of Maryland. A single superconducting proof mass is magnetically levitated against gravity or any other proof force. Its relative positions and orientations with respect to the platform are monitored by six superconducting inductance bridges sharing a single amplifier, called the Superconducting Quantum Interference Device (SQUID). The six degrees of freedom, the three linear acceleration components and the three angular acceleration components, of the platform are measured simultaneously. In order to improve the linearity and the dynamic range of the instrument, the demodulated outputs of the SQUID are fed back to appropriate levitation coils so that the proof mass remains at the null position for all six inductance bridges. The expected intrinsic noise of the instrument is 4 x 10(exp -12)m s(exp -2) Hz(exp -1/2) for linear acceleration and 3 x 10(exp -11) rad s(exp -2) Hz(exp -1/2) for angular acceleration in 1-g environment. In 0-g, the linear acceleration sensitivity of the superconducting accelerometer could be improved by two orders of magnitude. The design and the operating principle of a laboratory prototype of the new instrument is discussed.

Impact of multiple-dose versus single-dose inhaler devices on COPD patients’ persistence with long-acting β2-agonists: a dispensing database analysis

Science.gov (United States)

van Boven, Job FM; van Raaij, Joost J; van der Galiën, Ruben; Postma, Maarten J; van der Molen, Thys; Dekhuijzen, PN Richard; Vegter, Stefan

2014-01-01

Background: With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients’ persistence with long-acting β2-agonists (LABAs). Aims: To assess the impact of the type of inhaler device (multiple-dose versus single-dose inhalers) on 1-year persistence and switching patterns with LABAs. Methods: A retrospective observational cohort study was performed comparing a cohort of patients initiating multiple-dose inhalers and a cohort initiating single-dose inhalers. The study population consisted of long-acting bronchodilator naive COPD patients, initiating inhalation therapy with mono-LABAs (formoterol, indacaterol or salmeterol). Analyses were performed using pharmacy dispensing data from 1994 to 2012, obtained from the IADB.nl database. Study outcomes were 1-year persistence and switching patterns. Results were adjusted for initial prescriber, initial medication, dosing regimen and relevant comorbidities. Results: In all, 575 patients initiating LABAs were included in the final study cohort. Among them, 475 (83%) initiated a multiple-dose inhaler and 100 (17%) a single-dose inhaler. Further, 269 (47%) initiated formoterol, 9 (2%) indacaterol and 297 (52%) salmeterol. There was no significant difference in persistence between users of multiple-dose or single-dose inhalers (hazard ratio: 0.98, 95% confidence interval: 0.76–1.26, P=0.99). Over 80% re-started or switched medication. Conclusions: There seems no impact of inhaler device (multiple-dose versus single-dose inhalers) on COPD patients’ persistence with LABAs. Over 80% of patients who initially seemed to discontinue LABAs, re-started their initial medication or switched inhalers or medication within 1 year. PMID:25274453

Variable dose rate single-arc IMAT delivered with a constant dose rate and variable angular spacing

International Nuclear Information System (INIS)

Tang, Grace; Earl, Matthew A; Yu, Cedric X

2009-01-01

Single-arc intensity-modulated arc therapy (IMAT) has gained worldwide interest in both research and clinical implementation due to its superior plan quality and delivery efficiency. Single-arc IMAT techniques such as the Varian RapidArc(TM) deliver conformal dose distributions to the target in one single gantry rotation, resulting in a delivery time in the order of 2 min. The segments in these techniques are evenly distributed within an arc and are allowed to have different monitor unit (MU) weightings. Therefore, a variable dose-rate (VDR) is required for delivery. Because the VDR requirement complicates the control hardware and software of the linear accelerators (linacs) and prevents most existing linacs from delivering IMAT, we propose an alternative planning approach for IMAT using constant dose-rate (CDR) delivery with variable angular spacing. We prove the equivalence by converting VDR-optimized RapidArc plans to CDR plans, where the evenly spaced beams in the VDR plan are redistributed to uneven spacing such that the segments with larger MU weighting occupy a greater angular interval. To minimize perturbation in the optimized dose distribution, the angular deviation of the segments was restricted to ≤± 5 deg. This restriction requires the treatment arc to be broken into multiple sectors such that the local MU fluctuation within each sector is reduced, thereby lowering the angular deviation of the segments during redistribution. The converted CDR plans were delivered with a single gantry sweep as in the VDR plans but each sector was delivered with a different value of CDR. For four patient cases, including two head-and-neck, one brain and one prostate, all CDR plans developed with the variable spacing scheme produced similar dose distributions to the original VDR plans. For plans with complex angular MU distributions, the number of sectors increased up to four in the CDR plans in order to maintain the original plan quality. Since each sector was

Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing

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Ikeda H

2015-10-01

Full Text Available Hiroshi Ikeda,1 Kazuya Ishiguro,1 Tetsuyuki Igarashi,1 Yuka Aoki,1 Toshiaki Hayashi,1 Tadao Ishida,1 Yasushi Sasaki,1,2 Takashi Tokino,2 Yasuhisa Shinomura1 1Department of Gastroenterology, Rheumatology and Clinical Immunology, 2Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan Abstract: A 69-year-old man was diagnosed with IgG λ-type multiple myeloma (MM, Stage II in October 2010. He was treated with one cycle of high-dose dexamethasone. After three cycles of bortezomib, the patient exhibited slow elevations in the free light-chain levels and developed a significant new increase of serum M protein. Bone marrow cytogenetic analysis revealed a complex karyotype characteristic of malignant plasma cells. To better understand the molecular pathogenesis of this patient, we sequenced for mutations in the entire coding regions of 409 cancer-related genes using a semiconductor-based sequencing platform. Sequencing analysis revealed eight nonsynonymous somatic mutations in addition to several copy number variants, including CCND1 and RB1. These alterations may play roles in the pathobiology of this disease. This targeted next-generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients. Keywords: multiple myeloma, drug resistance, genome-wide sequencing, semiconductor sequencer, target therapy

Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies.

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Kuypers, Kim Pc; Dolder, Patrick C; Ramaekers, Johannes G; Liechti, Matthias E

2017-05-01

Previous placebo-controlled experimental studies have shown that a single dose of MDMA can increase emotional empathy in the multifaceted empathy test (MET) without affecting cognitive empathy. Although sufficiently powered to detect main effects of MDMA, these studies were generally underpowered to also validly assess contributions of additional parameters, such as sex, drug use history, trait empathy and MDMA or oxytocin plasma concentrations. The present study examined the robustness of the MDMA effect on empathy and investigated the moderating role of these additional parameters. Participants ( n = 118) from six placebo-controlled within-subject studies and two laboratories were included in the present pooled analysis. Empathy (MET), MDMA and oxytocin plasma concentrations were assessed after oral administration of MDMA (single dose, 75 or 125 mg). Trait empathy was assessed using the interpersonal reactivity index. We confirmed that MDMA increased emotional empathy at both doses without affecting cognitive empathy. This MDMA-related increase in empathy was most pronounced during presentation of positive emotions as compared with negative emotions. MDMA-induced empathy enhancement was positively related to MDMA blood concentrations measured before the test, but independent of sex, drug use history and trait empathy. Oxytocin concentrations increased after MDMA administration but were not associated with behavioral effects. The MDMA effects on emotional empathy were stable across laboratories and doses. Sex did not play a moderating role in this effect, and oxytocin levels, trait empathy and drug use history were also unrelated. Acute drug exposure was of significant relevance in the MDMA-induced emotional empathy elevation.

Genomic sequencing of uric acid metabolizing and clearing genes in relationship to xanthine oxidase inhibitor dose.

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Carroll, Matthew B; Smith, Derek M; Shaak, Thomas L

2017-03-01

It remains unclear why the dose of xanthine oxidase inhibitors (XOI) allopurinol or febuxostat varies among patients though they reach similar serum uric acid (SUA) goal. We pursued genomic sequencing of XOI metabolism and clearance genes to identify single-nucleotide polymorphisms (SNPs) relate to differences in XOI dose. Subjects with a diagnosis of Gout based on the 1977 American College of Rheumatology Classification Criteria for the disorder, who were on stable doses of a XOI, and who were at their goal SUA level, were enrolled. The primary outcome was relationship between SNPs in any of these genes to XOI dose. The secondary outcome was relationship between SNPs and change in pre- and post-treatment SUA. We enrolled 100 subjects. The average patient age was 68.6 ± 10.6 years old. Over 80% were men and 77% were Caucasian. One SNP was associated with a higher XOI dose: rs75995567 (p = 0.031). Two SNPs were associated with 300 mg daily of allopurinol: rs11678615 (p = 0.022) and rs3731722 on Aldehyde Oxidase (AO) (His1297Arg) (p = 0.001). Two SNPs were associated with a lower dose of allopurinol: rs1884725 (p = 0.033) and rs34650714 (p = 0.006). For the secondary outcome, rs13415401 was the only SNP related to a smaller mean SUA change. Ten SNPs were identified with a larger change in SUA. Though multiple SNPs were identified in the primary and secondary outcomes of this study, rs3731722 is known to alter catalytic function for some aldehyde oxidase substrates.

SAAS: Short Amino Acid Sequence - A Promising Protein Secondary Structure Prediction Method of Single Sequence

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Zhou Yuan Wu

2013-07-01

Full Text Available In statistical methods of predicting protein secondary structure, many researchers focus on single amino acid frequencies in α-helices, β-sheets, and so on, or the impact near amino acids on an amino acid forming a secondary structure. But the paper considers a short sequence of amino acids (3, 4, 5 or 6 amino acids as integer, and statistics short sequence's probability forming secondary structure. Also, many researchers select low homologous sequences as statistical database. But this paper select whole PDB database. In this paper we propose a strategy to predict protein secondary structure using simple statistical method. Numerical computation shows that, short amino acids sequence as integer to statistics, which can easy see trend of short sequence forming secondary structure, and it will work well to select large statistical database (whole PDB database without considering homologous, and Q3 accuracy is ca. 74% using this paper proposed simple statistical method, but accuracy of others statistical methods is less than 70%.

Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine

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Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.

2012-01-01

Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic anti-tumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589

Deep amplicon sequencing reveals mixed phytoplasma infection within single grapevine plants

DEFF Research Database (Denmark)

Nicolaisen, Mogens; Contaldo, Nicoletta; Makarova, Olga

2011-01-01

The diversity of phytoplasmas within single plants has not yet been fully investigated. In this project, deep amplicon sequencing was used to generate 50,926 phytoplasma sequences from 11 phytoplasma-infected grapevine samples from a PCR amplicon in the 5' end of the 16S region. After clustering ...

8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression: Results of a phase III randomized multicentre Italian trial

International Nuclear Information System (INIS)

Maranzano, Ernesto; Trippa, Fabio; Casale, Michelina; Costantini, Sara; Lupattelli, Marco; Bellavita, Rita; Marafioti, Luigi; Pergolizzi, Stefano; Santacaterina, Anna; Mignogna, Marcello; Silvano, Giovanni; Fusco, Vincenzo

2009-01-01

Background and purpose: In a previous randomized trial we showed that the short-course radiotherapy (RT) regimen of 8 Gy x 2 was feasible in patients with metastatic spinal cord compression (MSCC) and short life expectancy. This phase III trial was planned to determine whether in the same category of patients 8 Gy single-dose is as effective as 8 Gy x 2. Materials and methods: Three hundred and twenty-seven patients with MSCC and short life expectancy were randomly assigned to a short-course of 8 Gy x 2 or to 8 Gy single-dose RT. Median follow-up was 31 months (range, 4-58). Results: A total of 303 (93%) patients are assessable, 150 treated with the short-course and 153 with the single-dose RT. No difference in response was found between the two RT schedules adopted. Median duration of response was 5 and 4.5 months for short-course and single-dose RT (p = 0.4), respectively. The median overall survival was 4 months for all cases. Light acute toxicity was registered in a minority of cases. Late toxicity was never recorded. Conclusions: Both RT schedules adopted were effective. As already shown in several trials evaluating RT regimens in uncomplicated painful bone metastases, also MSCC patients may achieve palliation with minimal toxicity and inconvenience with a single-dose of 8 Gy.

Low-dose ketoconazole-fluconazole combination versus fluconazole in single doses for the treatment of vaginal candidiasis

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Jan Susilo

2011-08-01

Full Text Available Background: Vaginal candidiasis (VC is one of the most common fungal diseases. Candida albicans is the most common causative fungus and has been isolated from more than 80% of specimens obtained from women with VC. Ketoconazole is the first orally active antifungal, the dosage for VC is 200 mg twice daily for 5 days. Fluconazole is the newer oral antifungal, its dosage for VC is a single oral dose of 150 mg. Since fluconazole 150 mg is considerably expensive, a single dose of 100 mg ketoconazole and 40 mg fluconazole in combination has been tested for the treatment of VC. The results showed that from 11 women with confirmed VC, 1-2 weeks after drug administration, the mycological culture was negative in 8 women, positive in 1 woman, and 2 woman lost to follow-up. This promising result led to the present study with the objective to confirm the efficacy and safety of the above combination in a formal clinical trial.Methods: A total of 165 female patients, aged 18 years or older, with the diagnosis of VC from clinical symptoms (pruritus or burning or excessive discharge and positive microscopic smear (pseudohyphae and/or yeast cells were randomized to receive a single dose of either keto-fluco combination (n = 85 or fluconazole (n = 80, and returnedfor follow-up visit on day 8.Results: Among these patients, 39 patients had negative baseline culture, leaving 126 patients eligible for efficacy evaluation. The mycological eradication in the keto-fluco group was 74.5% (41 patients from a total of 55 patients with available mycological culture, while that in the fluconazole group was 70.2% (40 patients from 57 patients with available culture and this difference was not significant. The clinical favorable response (clinical cure and clinical improvement in the keto-fluco arm (n = 60 was 98.3%, while that in the fluconazole group (n = 66 was 100%. Adverse events were found in 5 patients, 3 patients in the keto-fluco group (3/85 = 3.5% and 2

An integrated multi−period planning of the production and transportation of multiple petroleum products in a single pipeline system

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Alberto Herrán

2011-01-01

Full Text Available A multiproduct pipeline provides an economic way to transport large volumes of refined petroleum products over long distances. In such a pipeline, different products are pumped back−to−back without any separation device between them. The sequence and lengths of such pumping runs must be carefully selected in order to meet market demands while minimizing pipeline operational costs and satisfying several constraints. The production planning and scheduling of the products at the refinery must also be synchronized with the transportation in order to avoid the usage of the system at some peak−hour time intervals. In this paper, we propose a multi−period mixed integer nonlinear programming (MINLP model for an optimal planning and scheduling of the production and transportation of multiple petroleum products from a refinery plant connected to several depots through a single pipeline system. The objective of this work is to generalize the mixed integer linear programming (MILP formulation proposed by Cafaro and Cerdá (2004, Computers and Chemical Engineering where only a single planning period was considered and the production planning and scheduling was not part of the decision process. Numerical examples show how the use of a single period model for a given time period may lead to infeasible solutions when it is used for the upcoming periods. These examples also show how integrating production planning with the transportation and the use of a multi−period model may result in a cost saving compared to using a single−period model for each period, independently.

The effect of single oral doses of duloxetine, reboxetine, and midodrine on the urethral pressure in healthy female subjects, using urethral pressure reflectometry

DEFF Research Database (Denmark)

Klarskov, Niels; Cerneus, Dirk; Sawyer, William

2018-01-01

AIMS: To evaluate the effect on urethral pressure of reference drugs known to reduce stress urinary incontinence symptoms by different effect size and mechanisms of action on urethral musculature under four test conditions in healthy female subjects using urethral pressure reflectometry. METHODS......: Healthy females aged 18-55 years were recruited by advertising for this phase 1, single site, placebo-controlled, randomized, four-period, crossover study. The interventions were single oral doses of 10 mg Midodrine, 80 mg Duloxetine, 12 mg Reboxetine, and placebo. The endpoints were the opening urethral...... pressure measured in each period at four time points (predose and 2, 5.5, and 9 h after dosing). RESULTS: Twenty-nine females were enrolled; 25 randomized and 24 completed the study. The opening urethral pressure was higher in all measurements with filled bladder compared with empty bladder, and during...

SU-F-BRCD-06: Multiple Anatomy Optimization of Accumulated Dose.

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Watkins, W T; Moore, J A; Sharma, M; Dial, C; Xu, H; Hugo, G D; Gordon, J J; Siebers, J V

2012-06-01

Multiple anatomy optimization (MAO) utilizing deformable dose accumulation on entire 4DCT data sets is implemented to overcome ambiguity between optimal dose defined on a single anatomy and optimal accumulated dose resulting from dose delivery to moving and deforming anatomy. Six lung cancer patients are planned using two methods of radiotherapy optimization: the internal target volume (ITV) envelope method and MAO, which simultaneously optimizes a single fluence for delivery to all 10 breathing phases such that the accumulated dose satisfies the plan objectives. Target dose is constrained to 70 Gy. The ITV-plan is optimized on a single breathing phase with the planning target volume defined as the ITV; the MAO target is the moving CTV. MAO is compared to single image ITV optimization based on the accumulated dose assuming equal monitor-units to each phase. Dose-volume differences between single image estimations and 10-image accumulation are examined. Single image optimal dose distributions overestimate target V70 by 4.2%±3.1% (average, one standard deviation) and in five of six cases ipsilateral lung V20 is underestimated (1.4%±0.9%). For these five cases, MAO increases V70 by 2.8%±2.5% (maximum of 6% increase in V70) and reduces ipsilateral lung V20 by up to 3% (average decrease of 1.2%±1.3%). Contralateral lung V20, esophagus V25, and heart V30 are also reduced by up to 5%, 3%, and 3%. For the sixth case, lung tumor motion is on the order of the dose voxel size (3mm), and MAO did not improve upon the ITV plan. Dose-volume optimization on a stationary image does not ensure accumulated dose coverage to the moving CTV. Multiple anatomy optimization can remove dose ambiguity and improve plan quality. P01CA11602 and Philips Medical Systems. © 2012 American Association of Physicists in Medicine.

Single dose oral flurbiprofen for acute postoperative pain in adults

Science.gov (United States)

Sultan, Asquad; McQuay, Henry J; Moore, R Andrew; Derry, Sheena

2014-01-01

Background Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions. The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25

Optimizing a single fixed dose of Iodine-131 in Graves' Disease (An Experience)

International Nuclear Information System (INIS)

Khan, S.H.

2007-01-01

low fixed dose of 185 MBq of I-131 was found to be significantly lower at 59.37%. On further analysis it was observed that the higher single fixed dose yielded a significantly higher cure rates irrespective of age, sex, thyroidal radioactive iodine uptake and pre-treatment hormonal status. There was no significant difference in the overall incidence of post-131 hypothyroidism at the end of 1 and 5 yeas following I-131 low or high single fixed dose of I-131. A steady rise in the percentage of patients becoming hypothyroid was noted between the 1 and 5 year period. The overall incidence of hypothyroidism at one and five years following I-131 therapy was found to be 48.76% and 82.64% respectively. The incidence of hypothyroidism appears to be higher in the present study, in comparison to several results reported in literature. This could be attributed to increased avidity of radioiodine to the available body iodine pool in the people living in the endemic area of iodine deficiency. Based on the results of this study we conclude that in an endemic area of iodine deficiency, a high single fixed dose of I-131 yields a higher cure rate as in non- endemic areas but the incidence of post I-131 hypothyroidism appears to be higher. However, this should not discourage physicians from choosing-I-131 as the first line of therapy for hyperthyroidism, considering the fact that hypothyroidism is easily managed by thyroid hormone supplementation, is cost effective and lastly, it (hypothyroidism) is part of the natural history of Graves' disease. (author)

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

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Scallion, Ralph; Moore, Keith A

2009-10-01

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

Draft Genome Sequences of Six Mycobacterium immunogenum, Strains Obtained from a Chloraminated Drinking Water Distribution System Simulator

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We report the draft genome sequences of six Mycobacterium immunogenum isolated from a chloraminated drinking water distribution system simulator subjected to changes in operational parameters. M. immunogenum, a rapidly growing mycobacteria previously reported as the cause of hyp...

High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA.

Science.gov (United States)

Kebschull, Justus M; Garcia da Silva, Pedro; Reid, Ashlan P; Peikon, Ian D; Albeanu, Dinu F; Zador, Anthony M

2016-09-07

Neurons transmit information to distant brain regions via long-range axonal projections. In the mouse, area-to-area connections have only been systematically mapped using bulk labeling techniques, which obscure the diverse projections of intermingled single neurons. Here we describe MAPseq (Multiplexed Analysis of Projections by Sequencing), a technique that can map the projections of thousands or even millions of single neurons by labeling large sets of neurons with random RNA sequences ("barcodes"). Axons are filled with barcode mRNA, each putative projection area is dissected, and the barcode mRNA is extracted and sequenced. Applying MAPseq to the locus coeruleus (LC), we find that individual LC neurons have preferred cortical targets. By recasting neuroanatomy, which is traditionally viewed as a problem of microscopy, as a problem of sequencing, MAPseq harnesses advances in sequencing technology to permit high-throughput interrogation of brain circuits. Copyright © 2016 Elsevier Inc. All rights reserved.

Simultaneous genomic identification and profiling of a single cell using semiconductor-based next generation sequencing

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Manabu Watanabe

2014-09-01

Full Text Available Combining single-cell methods and next-generation sequencing should provide a powerful means to understand single-cell biology and obviate the effects of sample heterogeneity. Here we report a single-cell identification method and seamless cancer gene profiling using semiconductor-based massively parallel sequencing. A549 cells (adenocarcinomic human alveolar basal epithelial cell line were used as a model. Single-cell capture was performed using laser capture microdissection (LCM with an Arcturus® XT system, and a captured single cell and a bulk population of A549 cells (≈106 cells were subjected to whole genome amplification (WGA. For cell identification, a multiplex PCR method (AmpliSeq™ SNP HID panel was used to enrich 136 highly discriminatory SNPs with a genotype concordance probability of 1031–35. For cancer gene profiling, we used mutation profiling that was performed in parallel using a hotspot panel for 50 cancer-related genes. Sequencing was performed using a semiconductor-based bench top sequencer. The distribution of sequence reads for both HID and Cancer panel amplicons was consistent across these samples. For the bulk population of cells, the percentages of sequence covered at coverage of more than 100× were 99.04% for the HID panel and 98.83% for the Cancer panel, while for the single cell percentages of sequence covered at coverage of more than 100× were 55.93% for the HID panel and 65.96% for the Cancer panel. Partial amplification failure or randomly distributed non-amplified regions across samples from single cells during the WGA procedures or random allele drop out probably caused these differences. However, comparative analyses showed that this method successfully discriminated a single A549 cancer cell from a bulk population of A549 cells. Thus, our approach provides a powerful means to overcome tumor sample heterogeneity when searching for somatic mutations.

Comparison of whole genome amplification techniques for human single cell exome sequencing.

Science.gov (United States)

Borgström, Erik; Paterlini, Marta; Mold, Jeff E; Frisen, Jonas; Lundeberg, Joakim

2017-01-01

Whole genome amplification (WGA) is currently a prerequisite for single cell whole genome or exome sequencing. Depending on the method used the rate of artifact formation, allelic dropout and sequence coverage over the genome may differ significantly. The largest difference between the evaluated protocols was observed when analyzing the target coverage and read depth distribution. These differences also had impact on the downstream variant calling. Conclusively, the products from the AMPLI1 and MALBAC kits were shown to be most similar to the bulk samples and are therefore recommended for WGA of single cells. In this study four commercial kits for WGA (AMPLI1, MALBAC, Repli-G and PicoPlex) were used to amplify human single cells. The WGA products were exome sequenced together with non-amplified bulk samples from the same source. The resulting data was evaluated in terms of genomic coverage, allelic dropout and SNP calling.

Single-dose radiosurgical treatment for hepatic metastases - therapeutic outcome of 138 treated lesions from a single institution

International Nuclear Information System (INIS)

Habermehl, Daniel; Herfarth, Klaus K; Bermejo, Justo Lorenzo; Hof, Holger; Rieken, Stefan; Kuhn, Sabine; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

2013-01-01

Local ablative therapies such as stereotactically guided single-dose radiotherapy or helical intensity-modulated radiotherapy (tomotherapy) with high single-doses are successfully applied in many centers in patients with liver metastasis not suitable for surgical resection. This study presents results from more than 10 years of clinical experience and evaluates long-term outcome and efficacy of this therapeutic approach. From 1997 to 2009 a total of 138 intrahepatic tumors of 90 patients were irradiated with single doses of 17 to 30 Gy (median dose 24 Gy). Median age of the patients was 64 years (range 31–89 years). Most frequent underlying tumor histologies were colorectal adenocarcinoma (70 lesions) and breast cancer (27 lesions). In 35 treatment sessions multiple targets were simultaneously irradiated (up to four lesions at once). Local progression-free (PFS) and overall survival (OS) after treatment were investigated using uni- and multiple survival regression models. Median overall survival of all patients was 24.3 months. Local PFS was 87%, 70% and 59% after 6, 12 and 18 months, respectively. Median time to local progression was 25.5 months. Patients with a single lesion and no further metastases at time of RT had a favorable median PFS of 43.1 months according to the Kaplan-Meier estimator. The type of tumor showed a statistical significant influence on local PFS, with a better prognosis for breast cancer histology than for colorectal carcinoma in uni- and multiple regression analysis (p = 0.05). Multiple regression analysis revealed no influence of planning target volume (PTV), patient age and radiation dose on local PFS. Treatment was well tolerated with no severe adverse events. This study confirms safety of SBRT in liver lesions, with 6- and 12 months local control of 87% and 70%. The dataset represents the clinical situation in a large oncology setting, with many competing treatment options and heterogeneous patient characteristics

Investigation of the role of TCF4 rare sequence variants in schizophrenia.

Science.gov (United States)

Basmanav, F Buket; Forstner, Andreas J; Fier, Heide; Herms, Stefan; Meier, Sandra; Degenhardt, Franziska; Hoffmann, Per; Barth, Sandra; Fricker, Nadine; Strohmaier, Jana; Witt, Stephanie H; Ludwig, Michael; Schmael, Christine; Moebus, Susanne; Maier, Wolfgang; Mössner, Rainald; Rujescu, Dan; Rietschel, Marcella; Lange, Christoph; Nöthen, Markus M; Cichon, Sven

2015-07-01

Transcription factor 4 (TCF4) is one of the most robust of all reported schizophrenia risk loci and is supported by several genetic and functional lines of evidence. While numerous studies have implicated common genetic variation at TCF4 in schizophrenia risk, the role of rare, small-sized variants at this locus-such as single nucleotide variants and short indels which are below the resolution of chip-based arrays requires further exploration. The aim of the present study was to investigate the association between rare TCF4 sequence variants and schizophrenia. Exon-targeted resequencing was performed in 190 German schizophrenia patients. Six rare variants at the coding exons and flanking sequences of the TCF4 gene were identified, including two missense variants and one splice site variant. These six variants were then pooled with nine additional rare variants identified in 379 European participants of the 1000 Genomes Project, and all 15 variants were genotyped in an independent German sample (n = 1,808 patients; n = 2,261 controls). These data were then analyzed using six statistical methods developed for the association analysis of rare variants. No significant association (P power analyses suggest that further research into the possible involvement of rare TCF4 sequence variants in schizophrenia risk is warranted by the assessment of larger cohorts with higher statistical power to identify rare variant associations. © 2015 Wiley Periodicals, Inc.

Single Dose of Consensus Hemagglutinin-Based Virus-Like Particles Vaccine Protects Chickens against Divergent H5 Subtype Influenza Viruses

Directory of Open Access Journals (Sweden)

Peipei Wu

2017-11-01

Full Text Available The H5 subtype highly pathogenic avian influenza (HPAI virus is one of the greatest threats to global poultry industry. To develop broadly protective H5 subunit vaccine, a recombinant consensus HA sequence (rHA was constructed and expressed in virus-like particles (rHA VLPs in the baculovirus-insect cell system. The efficacy of the rHA VLPs vaccine with or without immunopotentiator (CVCVA5 was assessed in chickens. Compared to the commercial Re6 or Re6-CVCVA5 vaccines, single dose immunization of chickens with rHA VLPs or rHA-CVCVA5 vaccines induced higher levels of serum hemagglutinin inhibition titers and neutralization titers, mucosal antibodies, IFN-γ and IL-4 cytokines in sera, and cytotoxic T lymphocyte responses. The rHA VLPs vaccine was superior to the commercial Re6 vaccine in conferring cross-protection against different clades of H5 subtype viruses. This study reports that H5 subtype consensus HA VLP single dose vaccination provides broad protection against HPAI virus in chickens.

Hypertrophic Cardiomyopathy After a Single Dose of Dexamethasone in a Preterm Infant

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Yusuf Kale

2015-08-01

Full Text Available Dexamethasone is widely used in preterm infants with severe pulmonary disease. Hypertrophic cardiomyopathy (HCM is a transient side effect observed after multiple doses of dexamethasone. We report a preterm infant with myocardial hypertrophy after a single dose of dexamethasone (0.5 mg/kg used to treat laryngeal edema secondary to prolonged intubation. A benign course was observed without left ventricular outflow tract obstruction and with recovery within 4 weeks. Myocardial effects of dexamethasone may be independent of dose and duration of treatment. The risk/benefit ratio must be carefully considered before using even a single dose of dexamethasone in preterm infants.

Coronary vasodilatory action after a single dose of nicorandil

NARCIS (Netherlands)

H. Suryapranata (Harry); P.W.J.C. Serruys (Patrick); P.J. de Feyter (Pim); P.D. Verdouw (Pieter); P.G. Hugenholtz (Paul)

1988-01-01

textabstractCoronary hemodynamics and vasodilatory effects on major epicardial arteries were investigated after a single dose of nicorandil in 22 patients undergoing cardiac catheterization for suspected coronary artery disease. Nicorandil, 20 mg, was administered sublingually to 11 consecutive

Gravitational waves from periodic three-body systems.

Science.gov (United States)

Dmitrašinović, V; Suvakov, Milovan; Hudomal, Ana

2014-09-05

Three bodies moving in a periodic orbit under the influence of Newtonian gravity ought to emit gravitational waves. We have calculated the gravitational radiation quadrupolar waveforms and the corresponding luminosities for the 13+11 recently discovered three-body periodic orbits in Newtonian gravity. These waves clearly allow one to distinguish between their sources: all 13+11 orbits have different waveforms and their luminosities (evaluated at the same orbit energy and body mass) vary by up to 13 orders of magnitude in the mean, and up to 20 orders of magnitude for the peak values.

High-throughput sequencing of three Lemnoideae (duckweeds chloroplast genomes from total DNA.

Directory of Open Access Journals (Sweden)

Wenqin Wang

Full Text Available BACKGROUND: Chloroplast genomes provide a wealth of information for evolutionary and population genetic studies. Chloroplasts play a particularly important role in the adaption for aquatic plants because they float on water and their major surface is exposed continuously to sunlight. The subfamily of Lemnoideae represents such a collection of aquatic species that because of photosynthesis represents one of the fastest growing plant species on earth. METHODS: We sequenced the chloroplast genomes from three different genera of Lemnoideae, Spirodela polyrhiza, Wolffiella lingulata and Wolffia australiana by high-throughput DNA sequencing of genomic DNA using the SOLiD platform. Unfractionated total DNA contains high copies of plastid DNA so that sequences from the nucleus and mitochondria can easily be filtered computationally. Remaining sequence reads were assembled into contiguous sequences (contigs using SOLiD software tools. Contigs were mapped to a reference genome of Lemna minor and gaps, selected by PCR, were sequenced on the ABI3730xl platform. CONCLUSIONS: This combinatorial approach yielded whole genomic contiguous sequences in a cost-effective manner. Over 1,000-time coverage of chloroplast from total DNA were reached by the SOLiD platform in a single spot on a quadrant slide without purification. Comparative analysis indicated that the chloroplast genome was conserved in gene number and organization with respect to the reference genome of L. minor. However, higher nucleotide substitution, abundant deletions and insertions occurred in non-coding regions of these genomes, indicating a greater genomic dynamics than expected from the comparison of other related species in the Pooideae. Noticeably, there was no transition bias over transversion in Lemnoideae. The data should have immediate applications in evolutionary biology and plant taxonomy with increased resolution and statistical power.

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

Science.gov (United States)

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

2008-05-01

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

Resolving the Complexity of Human Skin Metagenomes Using Single-Molecule Sequencing

Directory of Open Access Journals (Sweden)

Yu-Chih Tsai

2016-02-01

Full Text Available Deep metagenomic shotgun sequencing has emerged as a powerful tool to interrogate composition and function of complex microbial communities. Computational approaches to assemble genome fragments have been demonstrated to be an effective tool for de novo reconstruction of genomes from these communities. However, the resultant “genomes” are typically fragmented and incomplete due to the limited ability of short-read sequence data to assemble complex or low-coverage regions. Here, we use single-molecule, real-time (SMRT sequencing to reconstruct a high-quality, closed genome of a previously uncharacterized Corynebacterium simulans and its companion bacteriophage from a skin metagenomic sample. Considerable improvement in assembly quality occurs in hybrid approaches incorporating short-read data, with even relatively small amounts of long-read data being sufficient to improve metagenome reconstruction. Using short-read data to evaluate strain variation of this C. simulans in its skin community at single-nucleotide resolution, we observed a dominant C. simulans strain with moderate allelic heterozygosity throughout the population. We demonstrate the utility of SMRT sequencing and hybrid approaches in metagenome quantitation, reconstruction, and annotation.

Resolving the Complexity of Human Skin Metagenomes Using Single-Molecule Sequencing

Science.gov (United States)

Tsai, Yu-Chih; Deming, Clayton; Segre, Julia A.; Kong, Heidi H.; Korlach, Jonas

2016-01-01

ABSTRACT Deep metagenomic shotgun sequencing has emerged as a powerful tool to interrogate composition and function of complex microbial communities. Computational approaches to assemble genome fragments have been demonstrated to be an effective tool for de novo reconstruction of genomes from these communities. However, the resultant “genomes” are typically fragmented and incomplete due to the limited ability of short-read sequence data to assemble complex or low-coverage regions. Here, we use single-molecule, real-time (SMRT) sequencing to reconstruct a high-quality, closed genome of a previously uncharacterized Corynebacterium simulans and its companion bacteriophage from a skin metagenomic sample. Considerable improvement in assembly quality occurs in hybrid approaches incorporating short-read data, with even relatively small amounts of long-read data being sufficient to improve metagenome reconstruction. Using short-read data to evaluate strain variation of this C. simulans in its skin community at single-nucleotide resolution, we observed a dominant C. simulans strain with moderate allelic heterozygosity throughout the population. We demonstrate the utility of SMRT sequencing and hybrid approaches in metagenome quantitation, reconstruction, and annotation. PMID:26861018

Three-Phase and Six-Phase AC at the Lab Bench

Science.gov (United States)

Caplan, George M.

2009-01-01

Utility companies generate three-phase electric power, which consists of three sinusoidal voltages with phase angles of 0 degrees, 120 degrees, and 240 degrees. The ac generators described in most introductory textbooks are single-phase generators, so physics students are not likely to learn about three-phase power. I have developed a simple way…

Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

International Nuclear Information System (INIS)

Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya

2012-01-01

Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher’s exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade ≥3 acute or late toxicity was 6.8% (14 patients). Fisher’s exact test resulted in significant median splits for grade ≥3 toxicity at V12 = 3.78 cm 3 (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm 3 (RR 13, P=.0013), V20 = 0.11 cm 3 (RR 6, P=0.01), and V22 = 0.0 cm 3 (RR 13, P=.0013). The median split for D2.5 cm 3 (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm 3 . One hundred percent (n = 7) of grade ≥4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade ≥3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation recall reactions are

Rat skin carcinogenesis as a basis for estimating risks at low doses and dose rates of various types of radiation

International Nuclear Information System (INIS)

Burns, F.J.; Vanderlaan, M.; Strickland, P.; Albert, R.E.

1976-01-01

The recovery rate, age dependence and latent period for tumor induction in rat skin were measured for single and split doses of radiation, and the data were analyzed in terms of a general model in an attempt to estimate the expected tumor response for various types of radiation given at low dose rates for long periods of time. The dorsal skin of male rats was exposed to electrons, x rays, or protons in either single or split doses for several doses and the tumor responses were compared during 80 weeks of observation. A two stage model incorporating a reversible or recoverable mode was developed and various parameters in the model, including recovery rate, dose-response coefficients, and indices of age sensitivity, were evaluated experimentally. The measured parameters were then utilized to calculate expected tumor responses for exposure periods extending for duration of life. The calculations indicated that low dose rates could be markedly ( 1 / 100 to 1 / 1000 ) less effective in producing tumors than the same dose given in a short or acute exposure, although the magnitude of the reduction in effectiveness declines as the dose declines

Maternal methadone dosing schedule and fetal neurobehavior

Science.gov (United States)

Jansson, Lauren M.; DiPietro, Janet A.; Velez, Martha; Elko, Andrea; Knauer, Heather; Kivlighan, Katie T.

2008-01-01

Objective Daily methadone maintenance is the standard of care for opiate dependency during pregnancy. Previous research has indicated that single-dose maternal methadone administration significantly suppresses fetal neurobehaviors. The purpose of this study was to determine if split-dosing would have less impact on fetal neurobehavior than single-dose administration. Methods Forty methadone-maintained women were evaluated at peak and trough maternal methadone levels on single- and split-dosing schedules. Monitoring sessions occurred at 36 and 37 weeks gestation in a counterbalanced study design. Fetal measures included heart rate, variability, accelerations, motor activity and fetal movement-heart rate coupling (FM-FHR). Maternal measures included heart period, variability, skin conductance, respiration and vagal tone. Repeated measure analysis of variance was used to evaluate within-subject changes between split- and single-dosing regimens. Results All fetal neurobehavioral parameters were suppressed by maternal methadone administration, regardless of dosing regimen. Fetal parameters at peak were significantly lower during single vs. split methadone administration. FM-FHR coupling was less suppressed from trough to peak during split-dosing vs. single-dosing. Maternal physiologic parameters were generally unaffected by dosing condition. Conclusion Split- dosed fetuses displayed less neurobehavioral suppression from trough to peak maternal methadone levels as compared to single-dosed fetuses. Split-dosing may be beneficial for methadone-maintained pregnant women. PMID:19085624

Task related doses in Spanish pressurized water reactors over the period 1988-1992

Energy Technology Data Exchange (ETDEWEB)

O`Donnell, P.; Labarta, T.; Amor, I. [Subdireccion de Proteccion Radiologica, Madrid (Spain)

1995-03-01

In order to evaluate in depth the collective dose trend and its correlation with the effectiveness of the practical application of the ALARA principle in Spanish nuclear facilities, and base the different policy lines to promote this criteria, the CSN has fullfilled an analysis of the task related doses data over the period 1988-1992. Previously, the CSN had required to the utilities the compilation of their refuelling outage collective dose from 1988 according with a predeterminate number of tasks, in order to have available a representative and retrospective set of data in an homogeneous way and coherent with the international data banks on occupational exposure in NPP, as the CEC and the NEA ones. The scope of this analysis was the following: first, the collective dose summaries for outage tasks and departments for PWR and for BWR, including the minimum, maximum and average dose (and statistics data) for 18 different refuelling outage tasks and 12 personal departments for each generation of each type of rector, the task and department related collective dose trends in each plant and in each generation, and second, the dose reduction techniques having been used during that period in each plant and the relative level of adoption. In this presentation the main results and conclusions of the first part of the study are reviewed for PWR.

Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial.

Science.gov (United States)

Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C

2016-03-01

Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤ 30000, 30001-50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥ 4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas.

Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations

DEFF Research Database (Denmark)

Christrup, Lona Louring; Bonde, J; Rasmussen, S N

1992-01-01

Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr r...

Comparative Dose Accuracy of Durable and Patch Insulin Infusion Pumps

Science.gov (United States)

Jahn, Luis G.; Capurro, Jorge J.; Levy, Brian L.

2013-01-01

Background: As all major insulin pump manufacturers comply with the international infusion pump standard EN 60601-2-24:1998, there may be a general assumption that all pumps are equal in insulin-delivery accuracy. This research investigates single-dose and averaged-dose accuracy of incremental basal deliveries for one patch model and three durable models of insulin pumps. Method: For each pump model, discrete single doses delivered during 0.5 U/h basal rate infusion over a 20 h period were measured using a time-stamped microgravimetric system. Dose accuracy was analyzed by comparing single doses and time-averaged doses to specific accuracy thresholds (±5% to ±30%). Results: The percentage of single doses delivered outside accuracy thresholds of ±5%, ±10%, and ±20% were as follows: Animas OneTouch® Ping® (43.2%, 14.3%, and 1.8%, respectively), Roche Accu-Chek® Combo (50.6%, 24.4%, and 5.5%), Medtronic Paradigm® RevelTM/VeoTM (54.2%, 26.7%, and 6.6%), and Insulet OmniPod® (79.1%, 60.5%, and 34.9%). For 30 min, 1 h, and 2 h averaging windows, the percentage of doses delivered outside a ±15% accuracy were as follows: OneTouch Ping (1.0%, 0.4%, and 0%, respectively), Accu-Chek Combo (4.2%, 3.5%, and 3.1%), Paradigm Revel/Veo (3.9%, 3.1%, and 2.2%), and OmniPod (33.9%, 19.9%, and 10.3%). Conclusions: This technical evaluation demonstrates significant differences in single-dose and averaged-dose accuracy among the insulin pumps tested. Differences in dose accuracy were most evident between the patch pump model and the group of durable pump models. Of the pumps studied, the Animas OneTouch Ping demonstrated the best single-dose and averaged-dose accuracy. Further research on the clinical relevance of these findings is warranted. PMID:23911184

Hypermultiplets and hypercomplex geometry from six to three dimensions

International Nuclear Information System (INIS)

Rosseel, Jan; Proeyen, Antoine van

2004-01-01

The formulation of hypermultiplets that has been developed for five-dimensional matter multiplets is by dimensional reductions translated into the appropriate spinor language for six and four dimensions. We also treat the theories without actions that have the geometrical structure of hypercomplex geometry. The latter is the generalization of hyper-Kaehler geometry that does not require a Hermitian metric and hence corresponds to field equations without action. The translation tables of this paper allow the direct application of superconformal tensor calculus for the hypermultiplets using the available Weyl multiplets in six and four dimensions. Furthermore, the hypermultiplets in three dimensions that result from reduction of vector multiplets in four dimensions are considered, leading to a superconformal formulation of the c-map and an expression for the main geometric quantities of the hyper-Kaehler manifolds in the image of this map

Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

International Nuclear Information System (INIS)

Healy, W.L.; Lo, T.C.; Covall, D.J.; Pfeifer, B.A.; Wasilewski, S.A.

1990-01-01

Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700 centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy

YSOVAR: SIX PRE-MAIN-SEQUENCE ECLIPSING BINARIES IN THE ORION NEBULA CLUSTER

Energy Technology Data Exchange (ETDEWEB)

Morales-Calderon, M.; Stauffer, J. R.; Rebull, L. M. [Spitzer Science Center, California Institute of Technology, 1200 E California Blvd., Pasadena, CA 91125 (United States); Stassun, K. G. [Physics and Astronomy Department, Vanderbilt University, 1807 Station B, Nashville, TN 37235 (United States); Vrba, F. J. [U. S. Naval Observatory, Flagstaff Station, 10391 W. Naval Observatory Road, Flagstaff, AZ 86001-8521 (United States); Prato, L. [Lowell Observatory, 1400 West Mars Hill Road, Flagstaff, AZ 86001 (United States); Hillenbrand, L. A.; Carpenter, J. M. [Astronomy Department, California Institute of Technology, 1200 E California Blvd., Pasadena, CA 91125 (United States); Terebey, S.; Angione, J. [Department of Physics and Astronomy, California State University at Los Angeles, Los Angeles, CA 90032 (United States); Covey, K. R. [Department of Astronomy, Cornell University, 226 Space Sciences Building, Ithaca, NY 14853 (United States); Terndrup, D. M. [Department of Astronomy, The Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Gutermuth, R. [Department of Astronomy, University of Massachusetts, Amherst, MA 01003 (United States); Song, I. [Physics and Astronomy Department, University of Georgia, Athens, GA 30602-2451 (United States); Plavchan, P. [NASA Exoplanet Science Institute, California Institute of Technology, Pasadena, CA 91125 (United States); Marchis, F. [SETI Institute, Carl Sagan Center, 189 N San Bernado Av, Mountain View, CA 94043 (United States); Garcia, E. V. [Department of Physics, Fisk University, 1000 17th Ave. N, Nashville, TN 37208 (United States); Margheim, S. [Gemini Observatory, Southern Operations Center, Casilla 603, La Serena (Chile); Luhman, K. L. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); Irwin, J. M., E-mail: mariamc@cab.inta-csic.es [Harvard-Smithsonian Center for Astrophysics, 60 Garden St., Cambridge, MA 02138 (United States)

2012-07-10

Eclipsing binaries (EBs) provide critical laboratories for empirically testing predictions of theoretical models of stellar structure and evolution. Pre-main-sequence (PMS) EBs are particularly valuable, both due to their rarity and the highly dynamic nature of PMS evolution, such that a dense grid of PMS EBs is required to properly calibrate theoretical PMS models. Analyzing multi-epoch, multi-color light curves for {approx}2400 candidate Orion Nebula Cluster (ONC) members from our Warm Spitzer Exploration Science Program YSOVAR, we have identified 12 stars whose light curves show eclipse features. Four of these 12 EBs are previously known. Supplementing our light curves with follow-up optical and near-infrared spectroscopy, we establish two of the candidates as likely field EBs lying behind the ONC. We confirm the remaining six candidate systems, however, as newly identified ONC PMS EBs. These systems increase the number of known PMS EBs by over 50% and include the highest mass ({theta}{sup 1} Ori E, for which we provide a complete set of well-determined parameters including component masses of 2.807 and 2.797 M{sub Sun }) and longest-period (ISOY J053505.71-052354.1, P {approx} 20 days) PMS EBs currently known. In two cases ({theta}{sup 1} Ori E and ISOY J053526.88-044730.7), enough photometric and spectroscopic data exist to attempt an orbit solution and derive the system parameters. For the remaining systems, we combine our data with literature information to provide a preliminary characterization sufficient to guide follow-up investigations of these rare, benchmark systems.

YSOVAR: SIX PRE-MAIN-SEQUENCE ECLIPSING BINARIES IN THE ORION NEBULA CLUSTER

International Nuclear Information System (INIS)

Morales-Calderón, M.; Stauffer, J. R.; Rebull, L. M.; Stassun, K. G.; Vrba, F. J.; Prato, L.; Hillenbrand, L. A.; Carpenter, J. M.; Terebey, S.; Angione, J.; Covey, K. R.; Terndrup, D. M.; Gutermuth, R.; Song, I.; Plavchan, P.; Marchis, F.; García, E. V.; Margheim, S.; Luhman, K. L.; Irwin, J. M.

2012-01-01

Eclipsing binaries (EBs) provide critical laboratories for empirically testing predictions of theoretical models of stellar structure and evolution. Pre-main-sequence (PMS) EBs are particularly valuable, both due to their rarity and the highly dynamic nature of PMS evolution, such that a dense grid of PMS EBs is required to properly calibrate theoretical PMS models. Analyzing multi-epoch, multi-color light curves for ∼2400 candidate Orion Nebula Cluster (ONC) members from our Warm Spitzer Exploration Science Program YSOVAR, we have identified 12 stars whose light curves show eclipse features. Four of these 12 EBs are previously known. Supplementing our light curves with follow-up optical and near-infrared spectroscopy, we establish two of the candidates as likely field EBs lying behind the ONC. We confirm the remaining six candidate systems, however, as newly identified ONC PMS EBs. These systems increase the number of known PMS EBs by over 50% and include the highest mass (θ 1 Ori E, for which we provide a complete set of well-determined parameters including component masses of 2.807 and 2.797 M ☉ ) and longest-period (ISOY J053505.71–052354.1, P ∼ 20 days) PMS EBs currently known. In two cases (θ 1 Ori E and ISOY J053526.88–044730.7), enough photometric and spectroscopic data exist to attempt an orbit solution and derive the system parameters. For the remaining systems, we combine our data with literature information to provide a preliminary characterization sufficient to guide follow-up investigations of these rare, benchmark systems.

Serum tocopherol levels in very preterm infants after a single dose of vitamin E at birth.

Science.gov (United States)

Bell, Edward F; Hansen, Nellie I; Brion, Luc P; Ehrenkranz, Richard A; Kennedy, Kathleen A; Walsh, Michele C; Shankaran, Seetha; Acarregui, Michael J; Johnson, Karen J; Hale, Ellen C; Messina, Lynn A; Crawford, Margaret M; Laptook, Abbot R; Goldberg, Ronald N; Van Meurs, Krisa P; Carlo, Waldemar A; Poindexter, Brenda B; Faix, Roger G; Carlton, David P; Watterberg, Kristi L; Ellsbury, Dan L; Das, Abhik; Higgins, Rosemary D

2013-12-01

Our aim was to examine the impact of a single enteral dose of vitamin E on serum tocopherol levels. The study was undertaken to see whether a single dose of vitamin E soon after birth can rapidly increase the low α-tocopherol levels seen in very preterm infants. If so, this intervention could be tested as a means of reducing the risk of intracranial hemorrhage. Ninety-three infants vitamin E or placebo by gastric tube within 4 hours of birth. The vitamin E group received 50 IU/kg of vitamin E as dl-α-tocopheryl acetate (Aquasol E). The placebo group received sterile water. Blood samples were taken for measurement of serum tocopherol levels by high-performance liquid chromatography before dosing and 24 hours and 7 days after dosing. Eighty-eight infants received the study drug and were included in the analyses. The α-tocopherol levels were similar between the groups at baseline but higher in the vitamin E group at 24 hours (median 0.63 mg/dL vs. 0.42 mg/dL, P = .003) and 7 days (2.21 mg/dL vs 1.86 mg/dL, P = .04). There were no differences between groups in γ-tocopherol levels. At 24 hours, 30% of vitamin E infants and 62% of placebo infants had α-tocopherol levels vitamin E raised serum α-tocopherol levels, but to consistently achieve α-tocopherol levels >0.5 mg/dL, a higher dose or several doses of vitamin E may be needed.

Comparison of multi-echo and single-echo gradient-recalled echo sequences for SPIO-enhanced Liver MRI at 3 T

International Nuclear Information System (INIS)

Choi, J.S.; Kim, M.-J.; Kim, J.H.; Choi, J.-Y.; Chung, Y.E.; Park, M.-S.; Kim, K.W.

2010-01-01

Aim: To assess the utility of a T2*-weighted, multi-echo data imaging combination sequenced on superparamagnetic iron oxide (SPIO)-enhanced liver magnetic resonance imaging (MRI) using a 3 T system. Materials and methods: Fifty patients underwent SPIO-enhanced MRI at 3 T using T2*-weighted, single-echo, gradient-recalled echo (GRE) sequences [fast imaging with steady precession; repetition time (TR)/echo time (TE), 126 ms/9 ms; flip angle, 30 o ] and multi-echo GRE (multi-echo data image combination) sequences (TR/TE, 186 ms/9 ms; flip angle, 30 o ). Three radiologists independently reviewed the images in a random order. The sensitivity and accuracy for the detection of focal hepatic lesions (a total of 76 lesions in 33 patients; 48 solid lesions, 28 non-solid lesions) were compared by analysing the area under the receiver operating characteristic curves. Image artefacts (flow artefacts, susceptibility artefacts, dielectric artefacts, and motion artefacts), lesion conspicuity, and overall image quality were evaluated according to a four-point scale: 1, poor; 2, fair; 3, good; 4, excellent. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the lesions were compared. Results: Image artefacts were more frequent with single-echo GRE (p < 0.05). The mean scale of image quality assessment for flow, susceptibility, dielectric, and motion artefacts were 2.76, 3.13, 3.42, and 2.89 with singe-echo, respectively, compared with 3.47, 3.43, 3.47, and 3.39, respectively, with multi-echo GRE. There was no significant difference in lesion conspicuity between single-echo (3.15) and multi-echo (3.30) GRE sequences. The overall image quality was significantly (p < 0.05) better with multi-echo (3.37) than with single-echo GRE (2.89). The mean SNR and CNR of the lesions were significantly (p < 0.05) higher on multi-echo (79 ± 23 and 128 ± 59, respectively) images than on single-echo (38 ± 11 and 102 ± 44, respectively) images. Lesion detection accuracy and

The Properties of Long Period Variables in the LMC from MACHO

Energy Technology Data Exchange (ETDEWEB)

Fraser, O J; Hawley, S L; Cook, K H

2008-05-06

We present a new analysis of the long period variables in the Large Magellanic Cloud from the MACHO Variable Star Catalog. Three-quarters of our sample of evolved, variable stars have periodic light curves. We characterize the stars in our sample using the multiple periods found in their frequency spectra. Additionally, we use single-epoch 2MASS measurements to construct the average infrared light curves for different groups of these stars. Comparison with evolutionary models shows that stars on the RGB or the Early AGB often show non-periodic variability, but begin to pulsate with periods on the two shortest period-luminosity sequences (1 & 2) when they brighten to K{sub s} {approx} 13. The stars on the Thermally Pulsing AGB are more likely to pulsate with longer periods that lie on the next two P-L sequences (3 & 4), including the sequence associated with the Miras in the LMC. The Petersen diagram and its variants show that multi-periodic stars on each pair of these sequences (3 & 4, and 1 & 2), typically pulsate with periods associated only with that pair. The periods in these multi-periodic stars become longer and stronger as the star evolves. We further constrain the mechanism behind the long secondary periods (LSPs) seen in half of our sample, and find that there is a close match between the luminosity functions of the LSP stars and all of the stars in our sample, and that these star's pulsation amplitudes are relatively wavelength independent. Although this is characteristic of stellar multiplicity, the large number of these variables is problematic for that explanation.

Effective dose comparison between stitched and single FOV in CBCT protocols for complete dental arcade

International Nuclear Information System (INIS)

Soares, Maria Rosangela; Batista, Wilson Otto; Antonio, Patricia Lara de; Caldas, Linda V.E.; Maia, Ana F.

2015-01-01

Objective: The objective of this study was to assess and compare protocols with a single field of view and multiple stitched field of view with a similar clinical purpose by means of effective dose value. Materials and methods: Measurements of absorbed dose were performed with thermoluminescent dosemeters inserted in the position of organs/tissues of a female anthropomorphic phantom and from these values the effective dose was calculated, utilizing weighting factor tissue-ICRP 103 (2007). Results: The results obtained in this study for effective dose are within the range of 43.1 µSv and 111.5 µSv for equipment using protocols with single FOV and in the range of 44.5 µSv and 236.2 µSv for equipments that using protocols with stitched field of view. Conclusions: In terms of the value of effective dose, stitched FOV protocols do not have any advantage over the single field of view protocols. This results suggest the necessity for knowledge of the exposure parameters and effective dose values associated with each image protocol. - Highlights: • The study relies on the comparison of two protocols with similar goals of CBCT: stitched protocols and single protocols. • The stitched FOV protocol is more specific and it is good option when want imaging only of some dental units. • In relation the effective dose, single FOV protocols presents advantage over the stitched FOV protocols. • Know the exposure parameters and effective dose values associated with each image protocol is necessity for request the best CBCT tomographic image

Alteration of the systemic and microcirculation by a single oral dose of flavan-3-ols.

Directory of Open Access Journals (Sweden)

Kodai Ingawa

Full Text Available Several systematic reviews have reported that flow mediated dilatation (FMD was significantly increased in subjects after ingestion of chocolate that contains flavan-3-ols; however, the mechanisms responsible for this effect are not clear. In this study, we evaluated the effects of a single oral dose of flavan-3-ols on the systemic circulation and microcirculation in the cremaster muscle using intravital video microscopy in vivo. The cremaster muscle in rats was spread over a plastic chamber and a gastric tube was placed into the stomach. Blood flow in the cremasteric artery was determined using a laser Doppler flowmeter, while blood pressure and heart rate were measured by the tail-cuff method. Red blood cell velocity in arterioles and blood flow in the artery were significantly increased 5 min after the administration of 10 mg/kg flavan-3-ols compared with distilled water treatment. The number of capillaries recruited in the cremaster muscle was also significantly increased 15 min after treatment. Microscopic observation confirmed that increased shear stress on endothelial cells was maintained during the measurement period. The mean arterial blood pressure and heart rate were also significantly elevated soon after administration and returned to baseline before the end of the observation period. Plasma nitrate and nitrite levels, and NO phosphorylation of aortic tissue were significantly increased at 60 min after administration of flavan-3-ols. According to these results, a single oral dose of flavan-3-ols elevates blood pressure and flow transiently, and these effects induce NO production through increased shear stress on endothelial cells.

[Three dimensional finite element model of a modified posterior cervical single open-door laminoplasty].

Science.gov (United States)

Wang, Q; Yang, Y; Fei, Q; Li, D; Li, J J; Meng, H; Su, N; Fan, Z H; Wang, B Q

2017-06-06

Objective: To build a three-dimensional finite element models of a modified posterior cervical single open-door laminoplasty with short-segmental lateral mass screws fusion. Methods: The C(2)-C(7) segmental data were obtained from computed tomography (CT) scans of a male patient with cervical spondylotic myelopathy and spinal stenosis.Three-dimensional finite element models of a modified cervical single open-door laminoplasty (before and after surgery) were constructed by the combination of software package MIMICS, Geomagic and ABAQUS.The models were composed of bony vertebrae, articulating facets, intervertebral disc and associated ligaments.The loads of moments 1.5Nm at different directions (flexion, extension, lateral bending and axial rotation)were applied at preoperative model to calculate intersegmental ranges of motion.The results were compared with the previous studies to verify the validation of the models. Results: Three-dimensional finite element models of the modified cervical single open- door laminoplasty had 102258 elements (preoperative model) and 161 892 elements (postoperative model) respectively, including C(2-7) six bony vertebraes, C(2-3)-C(6-7) five intervertebral disc, main ligaments and lateral mass screws.The intersegmental responses at the preoperative model under the loads of moments 1.5 Nm at different directions were similar to the previous published data. Conclusion: Three-dimensional finite element models of the modified cervical single open- door laminoplasty were successfully established and had a good biological fidelity, which can be used for further study.

Six-state, three-level, six-fold ferromagnetic wire system

International Nuclear Information System (INIS)

Blachowicz, T.; Ehrmann, A.

2013-01-01

Six stable states at remanence were identified in iron wire samples of 6-fold spatial symmetry using micromagnetic simulations and the finite element method. Onion and domain-wall magnetic states were tailored by sample shape and guided by an applied magnetic field with a fixed in-plane direction. Different directions of externally applied magnetic fields revealed a tendency for stability or nonstability of the considered states. -- Highlights: ► In a ferromagnetic wire sample six stable states at remanence were discovered. ► Presented wires provide new effects not met in classical thin-layered solutions. ► The mechanism of working results from competing demagnetizing and exchange fields. ► For different physical conditions onion and domain-wall states were observed. ► Wire samples of 6-fold symmetry can lead to many-level information storage devices

Six-state, three-level, six-fold ferromagnetic wire system

Energy Technology Data Exchange (ETDEWEB)

Blachowicz, T., E-mail: tomasz.blachowicz@polsl.pl [Institute of Physics, Silesian University of Technology, 44-100 Gliwice (Poland); Ehrmann, A. [Faculty of Textile and Clothing Technology, Niederrhein University of Applied Sciences, 41065 Mönchengladbach (Germany)

2013-04-15

Six stable states at remanence were identified in iron wire samples of 6-fold spatial symmetry using micromagnetic simulations and the finite element method. Onion and domain-wall magnetic states were tailored by sample shape and guided by an applied magnetic field with a fixed in-plane direction. Different directions of externally applied magnetic fields revealed a tendency for stability or nonstability of the considered states. -- Highlights: ► In a ferromagnetic wire sample six stable states at remanence were discovered. ► Presented wires provide new effects not met in classical thin-layered solutions. ► The mechanism of working results from competing demagnetizing and exchange fields. ► For different physical conditions onion and domain-wall states were observed. ► Wire samples of 6-fold symmetry can lead to many-level information storage devices.

Reasons for Stopping Exclusive Breastfeeding Between Three and Six Months: A Qualitative Study.

Science.gov (United States)

Alianmoghaddam, Narges; Phibbs, Suzanne; Benn, Cheryl

Scant published qualitative literature exists focusing on why exclusive breastfeeding rates decline between three and six months. This study aims to develop an understanding of why exclusive breastfeeding tails off so dramatically between three and six months after birth in New Zealand. A generic qualitative methodology was employed in this study and social constructionism selected as the main epistemological framework underpinning the research. This study was carried out between September 2013 and July 2014, involving face-to-face interviews with 30 women who were characterised as highly motivated to complete six months exclusive breastfeeding prior to the birth of their child. In order to gain an in-depth understanding of the research material, thematic analysis of the interview transcripts was completed using manual coding techniques. After thematic analysis of the data four key themes were identified: 1) The good employee/good mother dilemma. 2) Breastfeeding is lovely, but six months exclusively is demanding. 3) Exclusive breastfeeding recommendations should be individualised. 4) Introducing solids early as a cultural practice. Most studies have linked barriers to six months exclusive breastfeeding to difficulties within the mother-infant dyad, as well as negative maternal socioeconomic and socio-demographic characteristics. However, this study has shown that the maintenance of six months exclusive breastfeeding is also challenging for this group of mothers who were socially advantaged, well-educated and highly motivated to breastfeed their babies exclusively for six months. Copyright © 2018 Elsevier Inc. All rights reserved.

DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

OpenAIRE

Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

2012-01-01

DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it possible to map SCEs at orders-of-magnitude greater resolution than was previously possible. On average, murine embryonic stem (mES) cells exhibit eight SCEs, which are detected at a resolution of up...

Vanuatu mortuary practices over three millenia : Lapita to early European contact period

International Nuclear Information System (INIS)

Valentin, F.; Spriggs, M.; Bedford, S.; Buckley, H.

2011-01-01

New discoveries and previously-unpublished data on burials from south, central, and north Vanuatu are reviewed in this paper, offering a synthesis of mortuary practices over three millennia, from Lapita to the early European contact period. Relying on five attributes describing the practices and behaviours (body and bone treatment, position and orientation of the body, ornaments and associated artefacts, and use of single or multiple burial), the analysis emphasizes two major episodes of structural changes in the overall funerary system following initial settlement of Vanuatu. The first occurred towards the end of the Lapita period and the second is indicated by the distinctiveness of the second millennium AD burials. A possible interpretation of these changes, following the lines of Thomas's 'genealogical approach' (2001) is proposed. (author). 70 refs., 5 figs.

The transition mechanism from a symmetric single period discharge to a period-doubling discharge in atmospheric helium dielectric-barrier discharge

International Nuclear Information System (INIS)

Zhang, Dingzong; Wang, Yanhui; Wang, Dezhen

2013-01-01

Period-doubling and chaos phenomenon have been frequently observed in atmospheric-pressure dielectric-barrier discharges. However, how a normal single period discharge bifurcates into period-doubling state is still unclear. In this paper, by changing the driving frequency, we study numerically the transition mechanisms from a normal single period discharge to a period-doubling state using a one-dimensional self-consistent fluid model. The results show that before a discharge bifurcates into a period-doubling state, it first deviates from its normal operation and transforms into an asymmetric single period discharge mode. Then the weaker discharge in this asymmetric discharge will be enhanced gradually with increasing of the frequency until it makes the subsequent discharge weaken and results in the discharge entering a period-doubling state. In the whole transition process, the spatial distribution of the charged particle density and the electric field plays a definitive role. The conclusions are further confirmed by changing the gap width and the amplitude of the applied voltage

The transition mechanism from a symmetric single period discharge to a period-doubling discharge in atmospheric helium dielectric-barrier discharge

Energy Technology Data Exchange (ETDEWEB)

Zhang, Dingzong; Wang, Yanhui; Wang, Dezhen [School of Physics and Optoelectronic Technology, Dalian University of Technology, Dalian 116024 (China)

2013-06-15

Period-doubling and chaos phenomenon have been frequently observed in atmospheric-pressure dielectric-barrier discharges. However, how a normal single period discharge bifurcates into period-doubling state is still unclear. In this paper, by changing the driving frequency, we study numerically the transition mechanisms from a normal single period discharge to a period-doubling state using a one-dimensional self-consistent fluid model. The results show that before a discharge bifurcates into a period-doubling state, it first deviates from its normal operation and transforms into an asymmetric single period discharge mode. Then the weaker discharge in this asymmetric discharge will be enhanced gradually with increasing of the frequency until it makes the subsequent discharge weaken and results in the discharge entering a period-doubling state. In the whole transition process, the spatial distribution of the charged particle density and the electric field plays a definitive role. The conclusions are further confirmed by changing the gap width and the amplitude of the applied voltage.

Management of urinary tract infections in pregnancy: a review with comments on single dose therapy.

Science.gov (United States)

Zinner, S H

1992-01-01

Most investigators agree that the adverse effects of urinary tract infections in pregnancy can be abrogated by effective early detection and treatment. However, the optimal methods for screening and treatment remain controversial. Although single-dose therapy has not been applied to pregnant women with acute pyelonephritis, most but not all studies which have compared single-dose with longer courses of beta-lactam or other antibiotics in pregnant asymptomatic bacteriuric women have shown no differences in outcome. This paper reviews recent trials of single-dose treatment of bacteriuria in pregnant women.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Macroscopic, pathologic and immunologic investigations of ten patients with carcinoma of oral cavity treated by a single large dose irradiation

International Nuclear Information System (INIS)

Mikuriya, Shuichi; Saito, Tsutomu; Konoeda, Koichi; Igarashi, Seishi; Hirohashi, Hitoshi

1979-01-01

The immunosuppressive effect of radiation has been emphasized. Although the irradiated cancer cells die gradually during the treatment, it is understood that they keep cancer specific antigenecity in that process. Another words, we assume that the immunologic capacity participates in the dying process of cancer cells by radiotherapy. We have been preferring to treat carcinoma by a single large dose irradiation method because this method does not impair the patient's immunologic capacity. On this time, we treated ten patients with carcinoma of oral cavity by this method and could obtain favorable results. 1) Ten patients with carcinoma of oral cavity classified in T1N0M0-T3N0M0 were irradiated by 4 - 10 MeV betatron electron. In seven patients, 2,500 - 3,000 rads were given at once and other three patients were irradiated with fractionated dose of 1,000 rads three times within two weeks (total 3,000 rads per two weeks). 2) Effects of a single large dose irradiation were remarkable and almost all cancer cells in these patients disappeared both macroscopically and pathologically. 3) According to the results of cellular immunity tests, numbers of peripheral lymphocytes, absolute numbers of fractionated T and B cells, and blastoid formation rate of lymphocytes stimulated by PHA in vitro were all increased and values obtained by four kinds of skin tests were also elevated after the radiations. These results indicate that the single large dose irradiation for these patients does not impair the immunologic capacity of the patients. (author)

Single-variant and multi-variant trend tests for genetic association with next-generation sequencing that are robust to sequencing error.

Science.gov (United States)

Kim, Wonkuk; Londono, Douglas; Zhou, Lisheng; Xing, Jinchuan; Nato, Alejandro Q; Musolf, Anthony; Matise, Tara C; Finch, Stephen J; Gordon, Derek

2012-01-01

As with any new technology, next-generation sequencing (NGS) has potential advantages and potential challenges. One advantage is the identification of multiple causal variants for disease that might otherwise be missed by SNP-chip technology. One potential challenge is misclassification error (as with any emerging technology) and the issue of power loss due to multiple testing. Here, we develop an extension of the linear trend test for association that incorporates differential misclassification error and may be applied to any number of SNPs. We call the statistic the linear trend test allowing for error, applied to NGS, or LTTae,NGS. This statistic allows for differential misclassification. The observed data are phenotypes for unrelated cases and controls, coverage, and the number of putative causal variants for every individual at all SNPs. We simulate data considering multiple factors (disease mode of inheritance, genotype relative risk, causal variant frequency, sequence error rate in cases, sequence error rate in controls, number of loci, and others) and evaluate type I error rate and power for each vector of factor settings. We compare our results with two recently published NGS statistics. Also, we create a fictitious disease model based on downloaded 1000 Genomes data for 5 SNPs and 388 individuals, and apply our statistic to those data. We find that the LTTae,NGS maintains the correct type I error rate in all simulations (differential and non-differential error), while the other statistics show large inflation in type I error for lower coverage. Power for all three methods is approximately the same for all three statistics in the presence of non-differential error. Application of our statistic to the 1000 Genomes data suggests that, for the data downloaded, there is a 1.5% sequence misclassification rate over all SNPs. Finally, application of the multi-variant form of LTTae,NGS shows high power for a number of simulation settings, although it can have

Relative oral bioavailability of morphine and naltrexone derived from crushed morphine sulfate and naltrexone hydrochloride extended-release capsules versus intact product and versus naltrexone solution: a single-dose, randomized-sequence, open-label, three-way crossover trial in healthy volunteers.

Science.gov (United States)

Johnson, Franklin K; Stark, Jeffrey G; Bieberdorf, Frederick A; Stauffer, Joe

2010-06-01

Morphine sulfate/sequestered naltrexone hydrochloride (HCl) (MS-sNT) extended-release fixed-dose combination capsules, approved by the US Food and Drug Administration (FDA) in August 2009 for chronic moderate to severe pain, contain extended-release morphine pellets with a sequestered core of the opioid antagonist naltrexone. MS-sNT was designed so that if the product is tampered with by crushing, the naltrexone becomes bioavailable to mitigate morphine-induced subjective effects, rendering the product less attractive for tampering. The primary aim of this study was to compare the oral bioavailability of naltrexone and its metabolite 6-beta-naltrexol, derived from crushed pellets from MS-sNT capsules, to naltrexone solution. This study also assessed the relative bioavailability of morphine from crushed pellets from MS-sNT capsules and that from the whole, intact product. This single-dose, randomized-sequence, open-label, 3-period, 3-treatment crossover trial was conducted in healthy volunteers. Adults admitted to the study center underwent a 10-hour overnight fast before study drug administration. Each subject received all 3 of the following treatments, 1 per session, separated by a 14-day washout: tampered pellets (crushed for >or=2 minutes with a mortar and pestle) from a 60-mg MS-sNT capsule (60 mg morphine/2.4 mg naltrexone); 60-mg whole, intact MS-sNT capsule; and oral naltrexone HCl (2.4 mg) solution. Plasma concentrations of naltrexone and 6-beta-naltrexol were measured 0 to 168 hours after administration. Morphine pharmaco-kinetics of crushed and whole pellets were determined 0 to 72 hours after administration. The analysis of relative bioavailability was based on conventional FDA criteria for assuming bioequivalence; that is, 90% CIs for ratios of geometric means (natural logarithm [In]-transformed C(max) and AUC) fell within the range of 80% to 125%. Subjects underwent physical examinations, clinical laboratory tests, and ECG at screening and study

Ocular Pharmacokinetics of Dorzolamide and Brinzolamide After Single and Multiple Topical Dosing: Implications for Effects on Ocular Blood FlowS⃞

Science.gov (United States)

Kadam, Rajendra S.; Jadhav, Gajanan; Ogidigben, Miller

2011-01-01

Ophthalmic carbonic anhydrase inhibitors have been shown to improve retinal and optic nerve blood flow. However, the relative tissue distributions of commercially available carbonic anhydrase inhibitors to the optic nerve are not known. The objective of this study was to compare the ocular pharmacokinetics and tissue distribution profiles of dorzolamide and brinzolamide after single and multiple topical applications. Pigmented rabbits were treated with single or multiple topical administrations of 30 μl of Trusopt (dorzolamide hydrochloride ophthalmic solution, 2%) to one eye and 30 μl of Azopt (brinzolamide ophthalmic suspension, 1%) to the other eye. Rabbits were euthanized at 10 predetermined time intervals over a period of 24 h, and ocular tissues and plasma samples were collected. For multiple dosing, rabbits were dosed twice per day with an 8-h interval between two doses, groups of rabbits were euthanized at 7, 14, and 21 days at 1 h after the last dose, and ocular tissues and plasma samples were collected. Drug levels in tissue samples were measured using liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters (Cmax, Tmax, and AUC0–24) were estimated by noncompartmental analysis. After a single dose, dorzolamide delivery (AUC0–24) to the aqueous humor, anterior sclera, posterior sclera, anterior retina, posterior retina, anterior vitreous, and optic nerve was 2-, 7-, 2.6-, 1.4-, 1.9-, 1.2-, and 9-fold higher than those of brinzolamide. Cmax was 2- to 5-fold higher for dorzolamide than that of brinzolamide in all of the ocular tissue. After multiple dosing, dorzolamide levels in the aqueous humor, sclera, retina, vitreous humor, and optic nerve were higher than those of brinzolamide, but statistical significance was achieved only with aqueous humor, vitreous humor, and optic nerve. Dorzolamide levels in the aqueous humor, anterior vitreous, posterior vitreous, and optic nerve were 1.4- to 3.2-, 2.4- to 2.7-, 2.2- to 4.5-, and 2.4- to

Collective dose of egyptian atomic energy workers during the period 1991-1995

Energy Technology Data Exchange (ETDEWEB)

Gomaa, M A; Youssef, S K [Reactor Division, and Radiation Protect. Dept., Nuclear Reseach Center Atomic Energy Authority, Cairo (Egypt)

1997-12-31

The collective dose to egyptian atomic energy authority workers during the period from 1991 - 1995 were statistically evaluated. The personnel dosimetry in use since 1957 for evaluating external exposure doses was mainly the Harwell blue badge and kodak radiation monitoring film for X and Gamma photons. The calibration sensitivity of the badge system was evaluated under the `AL` and/or `Pb/Sn alloy` filters. The results of calibration showed 15% errors in the predicted values for whole body effective doses. The statistical survey showed that the annual collective dose ranged between 0.83-1.54 man Sv. The annual limit of exposure presented 25-58% of the recommended annual limit by ICRP- 60 (1991). Details of the study will be considered in the text. 4 tabs.

One and three doses of propranolol a day in hypertension.

Science.gov (United States)

van den Brink, G; Boer, P; van Asten, P; Dorhout Mees, E J; Geyskes, G G

1980-01-01

In 26 patients with essential hypertension who were on continuous chlorthalidone therapy, 1 and 3 daily doses of propranolol were compared in a crossover study. Plasma propranolol levels and heart rates had larger daily fluctuations on single-dose therapy than on 3 times daily; plasma renin activity was more constant. There was no significant difference in blood pressures. Once-daily propranolol dosage was well tolerated and possibly gave less rise to the troublesome side effect of vivid dreaming.

SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

International Nuclear Information System (INIS)

Ding, C; Hrycushko, B; Jiang, S; Meyer, J; Timmerman, R

2014-01-01

Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm 3 ) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan, the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment

Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments.

Science.gov (United States)

Stambaugh, Cassandra; Nelms, Benjamin E; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

2013-09-01

The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments. VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤ 8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D99%), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found. For the motion amplitudes and periods obtained from the 4DCT, the interplay effect

Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments

International Nuclear Information System (INIS)

Stambaugh, Cassandra; Nelms, Benjamin E.; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

2013-01-01

Purpose: The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments.Methods: VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D 99% ), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found.Results: For the motion amplitudes and periods obtained from the

Single-dose Intramuscular-injection Toxicology Test of Water-soluble Carthami-flos and Cervi cornu parvum Pharmacopuncture in a Rat Model

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Sunju Park

2015-09-01

Full Text Available Objectives: The aim of the study is to investigate both the single-dose intramuscular injection toxicity and the approximate lethal dose of water-soluble Carthami-flos and Cervi cornu parvum pharmacopuncture (WCFC in male and female Sprague-Dawley (SD rats. Methods: The study was conducted at Biotoxtech Co. according to the Good Laboratory Practice (GLP regulation and the toxicity test guidelines of the Ministry of Food and Drug Safety (MFDS after approval of the Institutional Animal Care and Use Committee. Dosages for the control, high dose, middle dose and low dose groups were 0.5 mL/animal of saline and 0.5, 0.25 and 0.125 mL/animal of WCFC, respectively. WCFC was injected into the muscle of the left femoral region by using a disposable syringe (1 mL, 26 gauge. The general symptoms and mortality were observed 30 minutes, 1, 2, 4, and 6 hours after the first injection and then daily for 14 days after the injection. The body weights of the SD rats were measured on the day of the injection (before injection and on the third, seventh, and fourteenth days after the injection. Serum biochemical and hematologic tests, necropsy examinations, and histopathologic examinations at the injection site were performed after the observation period. Results: No deaths, abnormal clinical symptoms, or significant weight changes were observed in either male or female SD rats in the control or the test (0.125, 0.25, and 0.5 mL/animal groups during the observation period. No significant differences in hematology and serum biochemistry and no macroscopic abnormalities at necropsy were found. No abnormal reactions at injection sites were noted on the topical tolerance tests. Conclusion: The results of this single-dose toxicity study show that WCFC is safe, its lethal doses in male and female SD rats being estimated to be higher than 0.5 mL/animal.

Sequence Analysis of IncA/C and IncI1 Plasmids Isolated from Multidrug-Resistant Salmonella Newport Using Single-Molecule Real-Time Sequencing.

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Cao, Guojie; Allard, Marc; Hoffmann, Maria; Muruvanda, Tim; Luo, Yan; Payne, Justin; Meng, Kevin; Zhao, Shaohua; McDermott, Patrick; Brown, Eric; Meng, Jianghong

2018-04-05

Multidrug-resistant (MDR) plasmids play an important role in disseminating antimicrobial resistance genes. To elucidate the antimicrobial resistance gene compositions in A/C incompatibility complex (IncA/C) plasmids carried by animal-derived MDR Salmonella Newport, and to investigate the spread mechanism of IncA/C plasmids, this study characterizes the complete nucleotide sequences of IncA/C plasmids by comparative analysis. Complete nucleotide sequencing of plasmids and chromosomes of six MDR Salmonella Newport strains was performed using PacBio RSII. Open reading frames were assigned using prokaryotic genome annotation pipeline (PGAP). To understand genomic diversity and evolutionary relationships among Salmonella Newport IncA/C plasmids, we included three complete IncA/C plasmid sequences with similar backbones from Salmonella Newport and Escherichia coli: pSN254, pAM04528, and peH4H, and additional 200 draft chromosomes. With the exception of canine isolate CVM22462, which contained an additional IncI1 plasmid, each of the six MDR Salmonella Newport strains contained only the IncA/C plasmid. These IncA/C plasmids (including references) ranged in size from 80.1 (pCVM21538) to 176.5 kb (pSN254) and carried various resistance genes. Resistance genes floR, tetA, tetR, strA, strB, sul, and mer were identified in all IncA/C plasmids. Additionally, bla CMY-2 and sugE were present in all IncA/C plasmids, excepting pCVM21538. Plasmid pCVM22462 was capable of being transferred by conjugation. The IncI1 plasmid pCVM22462b in CVM22462 carried bla CMY-2 and sugE. Our data showed that MDR Salmonella Newport strains carrying similar IncA/C plasmids clustered together in the phylogenetic tree using chromosome sequences and the IncA/C plasmids from animal-derived Salmonella Newport contained diverse resistance genes. In the current study, we analyzed genomic diversities and phylogenetic relationships among MDR Salmonella Newport using complete plasmids and chromosome

Unveiling in situ interactions between marine protists and bacteria through single cell sequencing

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Martinez-Garcia, Manuel; Brazel, David; Poulton, Nicole J; Swan, Brandon K; Gomez, Monica Lluesma; Masland, Dashiell; Sieracki, Michael E; Stepanauskas, Ramunas

2012-01-01

Heterotrophic protists are a highly diverse and biogeochemically significant component of marine ecosystems, yet little is known about their species-specific prey preferences and symbiotic interactions in situ. Here we demonstrate how these previously unresolved questions can be addressed by sequencing the eukaryote and bacterial SSU rRNA genes from individual, uncultured protist cells collected from their natural marine environment and sorted by flow cytometry. We detected Pelagibacter ubique in association with a MAST-4 protist, an actinobacterium in association with a chrysophyte and three bacteroidetes in association with diverse protist groups. The presence of identical phylotypes among the putative prey and the free bacterioplankton in the same sample provides evidence for predator–prey interactions. Our results also suggest a discovery of novel symbionts, distantly related to Rickettsiales and the candidate divisions ZB3 and TG2, associated with Cercozoa and Chrysophyta cells. This study demonstrates the power of single cell sequencing to untangle ecological interactions between uncultured protists and prokaryotes. PMID:21938022

In vivo assessment of the gastric mucosal tolerance dose after single fraction, small volume irradiation of liver malignancies by computed tomography-guided, high-dose-rate brachytherapy

International Nuclear Information System (INIS)

Streitparth, Florian; Pech, Maciej; Boehmig, Michael; Ruehl, Ricarda; Peters, Nils; Wieners, Gero; Steinberg, Johannes; Lopez-Haenninen, Enrique; Felix, Roland; Wust, Peter; Ricke, Jens

2006-01-01

Purpose: The aim of this study was to assess the tolerance dose of gastric mucosa for single-fraction computed tomography (CT)-guided, high-dose-rate (HDR) brachytherapy of liver malignancies. Methods and Materials: A total of 33 patients treated by CT-guided HDR brachytherapy of liver malignancies in segments II and/or III were included. Dose planning was performed upon a three-dimensional CT data set acquired after percutaneous applicator positioning. All patients received gastric protection post-treatment. For further analysis, the contours of the gastric wall were defined in every CT slice using Brachyvision Software. Dose-volume histograms were calculated for each treatment and correlated with clinical data derived from questionnaires assessing Common Toxicity Criteria (CTC). All patients presenting symptoms of upper GI toxicity were examined endoscopically. Results: Summarizing all patients the minimum dose applied to 1 ml of the gastric wall (D 1ml ) ranged from 6.3 to 34.2 Gy; median, 14.3 Gy. Toxicity was present in 18 patients (55%). We found nausea in 16 (69%), emesis in 9 (27%), cramping in 13 (39%), weight loss in 12 (36%), gastritis in 4 (12%), and ulceration in 5 patients (15%). We found a threshold dose D 1ml of 11 Gy for general gastric toxicity and 15.5 Gy for gastric ulceration verified by an univariate analysis (p = 0.01). Conclusions: For a single fraction, small volume irradiation we found in the upper abdomen a threshold dose D 1ml of 15.5 Gy for the clinical endpoint ulceration of the gastric mucosa. This in vivo assessment is in accordance with previously published tolerance data

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

Science.gov (United States)

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2015-01-01

Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

Directory of Open Access Journals (Sweden)

Jing Hao

Full Text Available Fixed-dose combinations (FDC contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed.Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients.New molecular entities (NMEs, new therapeutic biologics license applications (BLAs and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC and only already marketed drugs (Non-NMEs-FDC. Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed.During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31 after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39 before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24 years to the patent and exclusivity life of the single active ingredients in the combination.FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

Periodically Driven Array of Single Rydberg Atoms

Science.gov (United States)

Basak, Sagarika; Chougale, Yashwant; Nath, Rejish

2018-03-01

An array of single Rydberg atoms driven by a temporally modulated atom-field detuning is studied. The periodic modulation effectively modifies the Rabi coupling, leading to unprecedented dynamics in the presence of Rydberg-Rydberg interactions, in particular, blockade enhancement, antiblockades, and state-dependent population trapping. Interestingly, the Schrieffer-Wolf transformation reveals a fundamental process in Rydberg gases, correlated Rabi coupling, which stems from the extended nature of the Rydberg-Rydberg interactions. Also, the correlated coupling provides an alternative depiction for the Rydberg blockade, exhibiting a nontrivial behavior in the presence of periodic modulation. The dynamical localization of a many-body configuration in a driven Rydberg lattice is discussed.

Single nucleotide polymorphism discovery from expressed sequence tags in the waterflea Daphnia magna

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Souche Erika L

2011-06-01

Full Text Available Abstract Background Daphnia (Crustacea: Cladocera plays a central role in standing aquatic ecosystems, has a well known ecology and is widely used in population studies and environmental risk assessments. Daphnia magna is, especially in Europe, intensively used to study stress responses of natural populations to pollutants, climate change, and antagonistic interactions with predators and parasites, which have all been demonstrated to induce micro-evolutionary and adaptive responses. Although its ecology and evolutionary biology is intensively studied, little is known on the functional genomics underpinning of phenotypic responses to environmental stressors. The aim of the present study was to find genes expressed in presence of environmental stressors, and target such genes for single nucleotide polymorphic (SNP marker development. Results We developed three expressed sequence tag (EST libraries using clonal lineages of D. magna exposed to ecological stressors, namely fish predation, parasite infection and pesticide exposure. We used these newly developed ESTs and other Daphnia ESTs retrieved from NCBI GeneBank to mine for SNP markers targeting synonymous as well as non synonymous genetic variation. We validate the developed SNPs in six natural populations of D. magna distributed at regional scale. Conclusions A large proportion (47% of the produced ESTs are Daphnia lineage specific genes, which are potentially involved in responses to environmental stress rather than to general cellular functions and metabolic activities, or reflect the arthropod's aquatic lifestyle. The characterization of genes expressed under stress and the validation of their SNPs for population genetic study is important for identifying ecologically responsive genes in D. magna.

Single dose of bisphosphonate preserves gains in bone mass following cessation of sclerostin antibody in Brtl/+ osteogenesis imperfecta model.

Science.gov (United States)

Perosky, Joseph E; Khoury, Basma M; Jenks, Terese N; Ward, Ferrous S; Cortright, Kai; Meyer, Bethany; Barton, David K; Sinder, Benjamin P; Marini, Joan C; Caird, Michelle S; Kozloff, Kenneth M

2016-12-01

Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3week old Brtl/+ and wild type mice for 5weeks with SclAb, and then withdrew treatment for an additional 6weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6weeks following cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

Low doses of six toxicants change plant size distribution in dense populations of Lactuca sativa.

Science.gov (United States)

Belz, Regina G; Patama, Marjo; Sinkkonen, Aki

2018-08-01

Toxicants are known to have negligible or stimulatory, i.e. hormetic, effects at low doses below those that decrease the mean response of a plant population. Our earlier observations indicated that at such low toxicant doses the growth of very fast- and slow-growing seedlings is selectively altered, even if the population mean remains constant. Currently, it is not known how common these selective low-dose effects are, whether they are similar among fast- and slow-growing seedlings, and whether they occur concurrently with hormetic effects. We tested the response of Lactuca sativa in complete dose-response experiments to six different toxicants at doses that did not decrease population mean and beyond. The tested toxicants were IAA, parthenin, HHCB, 4-tert-octylphenol, glyphosate, and pelargonic acid. Each experiment consisted of 14,400-16,800 seedlings, 12-14 concentrations, 24 replicates per concentration and 50 germinated seeds per replicate. We analyzed the commonness of selective low-dose effects and explored if toxic effects and hormetic stimulation among fast- and slow-growing individuals occurred at the same concentrations as they occur at the population level. Irrespective of the observed response pattern and toxicant, selective low-dose effects were found. Toxin effects among fast-growing individuals usually started at higher doses compared to the population mean, while the opposite was found among slow-growing individuals. Very low toxin exposures tended to homogenize plant populations due to selective effects, while higher, but still hormetic doses tended to heterogenize plant populations. Although the extent of observed size segregation varied with the specific toxin tested, we conclude that a dose-dependent alteration in size distribution of a plant population may generally apply for many toxin exposures. Copyright © 2018 Elsevier B.V. All rights reserved.

Single dose systemic acetaminophen to improve patient reported quality of recovery after ambulatory segmental mastectomy: A prospective, randomized, double-blinded, placebo controlled, clinical trial.

Science.gov (United States)

De Oliveira, Gildasio S; Rodes, Meghan E; Bialek, Jane; Kendall, Mark C; McCarthy, Robert J

2017-11-15

Few systemic drug interventions are efficacious to improve patient reported quality of recovery after ambulatory surgery. We aimed to evaluate whether a single dose systemic acetaminophen improve quality of recovery in female patients undergoing ambulatory breast surgery. We hypothesized that patients receiving a single dose systemic acetaminophen at the end of the surgical procedure would have a better global quality of postsurgical recovery compared to the ones receiving saline. The study was a prospective randomized double blinded, placebo controlled, clinical trial. Healthy female subjects were randomized to receive 1 g single dose systemic acetaminophen at the end of the surgery or the same volume of saline. The primary outcome was the Quality of Recovery 40 (QOR-40) questionnaire at 24 hours after surgery. Other data collected included opioid consumption and pain scores. Data were analyzed using group t tests and the Wilcoxon exact test. The association between opioid consumption and quality of recovery was evaluated using Spearman rho. P quality of recovery, P = .007. A single dose of systemic acetaminophen improves patient reported quality of recovery after ambulatory breast surgery. The use of systemic acetaminophen is an efficacious strategy to improve patient perceived quality of postsurgical recovery and analgesic outcomes after hospital discharge for ambulatory breast surgery. © 2017 Wiley Periodicals, Inc.

Three Phase Six-Switch PWM Buck Rectifier with Power Factor Improvement

DEFF Research Database (Denmark)

Zafar Ullah Khan, M; Mohsin Naveed, M.; Hussain, Dil Muhammad Akbar

2013-01-01

Conventional Phase Controlled Rectifier injects low order current harmonics into the AC mains. Large size filtering components are required to attenuate these harmonics. In this paper, Three Phase Six-Switch PWM Buck Rectifier[1] is presented which operates at nearly unity power factor and provides...

Analytical determination of bifurcations of periodic solution in three-degree-of-freedom vibro-impact systems with clearance

International Nuclear Information System (INIS)

Liu, Yongbao; Wang, Qiang; Xu, Huidong

2017-01-01

The smooth bifurcation and non-smooth grazing bifurcation of periodic solution of three-degree-of-freedom vibro-impact systems with clearance are studied in this paper. Firstly, six-dimensional Poincaré maps are established through choosing suitable Poincaré section and solving periodic solutions of vibro-impact system. Then, as the analytic expressions of all eigenvalues of Jacobi matrix of six-dimensional map are unavailable, the numerical calculations to search for the critical bifurcation values point by point is a laborious job based on the classical critical criterion described by the properties of eigenvalues. To overcome the difficulty from the classical bifurcation criteria, the explicit critical criterion without using eigenvalues calculation of high-dimensional map is applied to determine bifurcation points of Co-dimension-one bifurcations and Co-dimension-two bifurcations, and then local dynamical behaviors of these bifurcations are further analyzed. Finally, the existence of the grazing periodic solution of the vibro-impact system and grazing bifurcation point are analyzed, the discontinuous grazing bifurcation behavior is studied based on the compound normal form map near the grazing point, the discontinuous jumping phenomenon and the co-existing multiple solutions near the grazing bifurcation point are revealed.

Quality assurance of rifampicin-containing fixed-drug combinations in South Africa: dosing implications.

Science.gov (United States)

Court, R; Chirehwa, M T; Wiesner, L; Wright, B; Smythe, W; Kramer, N; McIlleron, H

2018-05-01

Rifampicin (RMP) drives treatment response in drug-susceptible tuberculosis. Low RMP concentrations increase the risk of poor outcomes, and drug quality needs to be excluded as a contributor to low RMP exposure. We performed an open-label, three-way cross-over study of three licensed RMP-containing formulations widely used in South Africa to evaluate the bioavailability of RMP in a two-drug fixed-dose combination tablet (2FDC) and a four-drug FDC (4FDC) against a single-drug reference. RMP dosed at 600 mg was administered 2 weeks apart in random sequence. Plasma RMP concentrations were measured pre-dose and 1, 2, 3, 4, 6, 8 and 12 h post-dose. The area under the concentration-time curve (AUC0-12) of the FDCs was compared to the single drug reference. Simulations were used to predict the impact of our findings. Twenty healthy volunteers (median age 22.8 years, body mass index 24.2 kg/m2) completed the study. The AUC0-12 of the 4FDC/reference (geometric mean ratio [GMR] 78%, 90%CI 69-89) indicated an average 20% reduction in RMP bioavailability in the 4FDC. The 2FDC/reference (GMR 104%, 90%CI 97-111) was bioequivalent. Simulations suggested dose adjustments to compensate for the poor bioavailability of RMP with the 4FDC, and revised weight-band doses to prevent systematic underdosing of low-weight patients. Post-marketing surveillance of in vivo bioavailability of RMP and improved weight band-based dosing are recommended.

Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

2012-08-01

To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

Task related doses in spanish light water reactors over the period 1990-1996