308 research outputs found
Population Pharmacokinetics and Pharmacodynamics Modeling of Torasemide and Furosemide After Oral Repeated Administration in Healthy Dogs
Torasemide is a loop diuretic licensed in dogs for cardiogenic pulmonary oedema. The aim of this pharmacokinetic-pharmacodynamic (PK/PD) study was to define an optimally effective dosage regimen based on preclinical data. In a first study, 5 dogs received once-daily oral torasemide (0, 0.1, 0.2, 0.4, 0.8 mg/kg/day) for 14 days. A second study compared once-daily oral torasemide (0, 0.1, 0.2, 0.3, 0.4 mg/kg/day) to twice-daily furosemide (1, 2, 4, 8 mg/kg/day). For all doses of the second study, 11 dogs received a first day of treatment, followed by a 3 day washout and resumed daily treatment for 10 days (until Day 14). Blood and urine were collected to measure urinary torasemide excretion and plasma torasemide concentrations and daily diuresis and natriuresis. Torasemide PK was linear. After rapid absorption (Tmax 0.5–1 h), 61% of the bioavailable torasemide was eliminated unchanged in urine. Diuresis and natriuresis observed with torasemide were similar to the ones obtained after furosemide (daily dose-ratios: 1/20 to 1/10). The average diuresis increased from baseline (220 ± 53 mL/day for 10 kg dogs) to 730 ±120 mL after the first torasemide administration and up to 1150 ± 252 mL after 10 administrations at the highest dose. At higher doses (≥0.3 mg/kg/day), daily diureses after 10 diuretic treatment-days were higher than Day 1 and variable between dogs; in contrast, diureses remained constant over time and less variable for doses up to 0.2 mg/kg/day. Natriuresis peaked after the first day and decreased dramatically after the 2nd treatment-day then stabilized to a value close to baseline, except for 0.4 mg/kg/day. Urinary torasemide excretion predicted pharmacodynamics better than plasma concentrations. The decrease in natriuresis observed was successfully modeled using a resistance mechanism; this is likely due to a reabsorption of sodium which did not seem however to affect the volume of urine excreted. For a daily target diuresis of 460 mL/dog/day in severe pulmonary oedema (net fluid loss 240 mL/dog/day), a computed dose of 0.26 mg/kg/day (3.5 mg/kg/day furosemide-equivalent) was selected for clinical studies. Due to high inter-individual variability in diureses at doses ≥0.3 mg/kg, higher doses should be limited to 3–5 days to avoid supra-clinical effects in high responders
Multiscaling analysis of ferroelectric domain wall roughness
Using multiscaling analysis, we compare the characteristic roughening of
ferroelectric domain walls in PZT thin films with numerical simulations of
weakly pinned one-dimensional interfaces. Although at length scales up to a
length scale greater or equal to 5 microns the ferroelectric domain walls
behave similarly to the numerical interfaces, showing a simple mono-affine
scaling (with a well-defined roughness exponent), we demonstrate more complex
scaling at higher length scales, making the walls globally multi-affine
(varying roughness exponent at different observation length scales). The
dominant contributions to this multi-affine scaling appear to be very localized
variations in the disorder potential, possibly related to dislocation defects
present in the substrate.Comment: 5 pages, 4 figure
The DICE calibration project: design, characterization, and first results
We describe the design, operation, and first results of a photometric
calibration project, called DICE (Direct Illumination Calibration Experiment),
aiming at achieving precise instrumental calibration of optical telescopes. The
heart of DICE is an illumination device composed of 24 narrow-spectrum,
high-intensity, light-emitting diodes (LED) chosen to cover the
ultraviolet-to-near-infrared spectral range. It implements a point-like source
placed at a finite distance from the telescope entrance pupil, yielding a flat
field illumination that covers the entire field of view of the imager. The
purpose of this system is to perform a lightweight routine monitoring of the
imager passbands with a precision better than 5 per-mil on the relative
passband normalisations and about 3{\AA} on the filter cutoff positions. The
light source is calibrated on a spectrophotometric bench. As our fundamental
metrology standard, we use a photodiode calibrated at NIST. The radiant
intensity of each beam is mapped, and spectra are measured for each LED. All
measurements are conducted at temperatures ranging from 0{\deg}C to 25{\deg}C
in order to study the temperature dependence of the system. The photometric and
spectroscopic measurements are combined into a model that predicts the spectral
intensity of the source as a function of temperature. We find that the
calibration beams are stable at the level -- after taking the slight
temperature dependence of the LED emission properties into account. We show
that the spectral intensity of the source can be characterised with a precision
of 3{\AA} in wavelength. In flux, we reach an accuracy of about 0.2-0.5%
depending on how we understand the off-diagonal terms of the error budget
affecting the calibration of the NIST photodiode. With a routine 60-mn
calibration program, the apparatus is able to constrain the passbands at the
targeted precision levels.Comment: 25 pages, 27 figures, accepted for publication in A&
The OPERA experiment Target Tracker
The main task of the Target Tracker detector of the long baseline neutrino
oscillation OPERA experiment is to locate in which of the target elementary
constituents, the lead/emulsion bricks, the neutrino interactions have occurred
and also to give calorimetric information about each event. The technology used
consists in walls of two planes of plastic scintillator strips, one per
transverse direction. Wavelength shifting fibres collect the light signal
emitted by the scintillator strips and guide it to both ends where it is read
by multi-anode photomultiplier tubes. All the elements used in the construction
of this detector and its main characteristics are described.Comment: 25 pages, submitted to Nuclear Instrument and Method
Nanoscale Piezoelectric Properties of Self-Assembled Fmoc-FF Peptide Fibrous Networks
Fibrous peptide networks, such as the structural framework of self-assembled fluorenylmethyloxycarbonyl diphenylalanine (Fmoc-FF) nanofibrils, have mechanical properties that could successfully mimic natural tissues, making them promising materials for tissue engineering scaffolds. These nanomaterials have been determined to exhibit shear piezoelectricity using piezoresponse force microscopy, as previously reported for FF nanotubes. Structural analyses of Fmoc-FF nanofibrils suggest that the observed piezoelectric response may result from the noncentrosymmetric nature of an underlying β-sheet topology. The observed piezoelectricity of Fmoc-FF fibrous networks is advantageous for a range of biomedical applications where electrical or mechanical stimuli are required. © 2015 American Chemical Society
Study of 2 beta-decay of Mo-100 and Se-82 using the NEMO3 detector
After analysis of 5797 h of data from the detector NEMO3, new limits on neutrinoless double beta decay of Mo-100 (T-1/2 > 3.1 x 10(23) y, 90% CL) and Se-82 (T-1/2 > 1.4 x 10(23) y, 90% CL) have been obtained. The corresponding limits on the effective majorana neutrino mass are: 1.4 x 10(22) y (90% CL) for Mo-100 and T-1/2 > 1.2 x 10(22) y (90% CL) for Se-82. Corresponding bounds on the Majoron-neutrino coupling constant are < (0.5-0.9) x 10(- 4) and <(0.7-1.6) x 10(- 4). Two-neutrino 2beta-decay half-lives have been measured with a high accuracy, (T1/2Mo)-Mo-100 = [7.68 +/- 0.02(stat) +/- 0.54(syst)] x 10(18) y and (T1/2Se)-Se-82 = [10.3 +/- 0.3(stat) +/- 0.7(syst)] x 10(19) y. (C) 2004 MAIK "Nauka/Interperiodica"
Study of 2b-decay of Mo-100 and Se-82 using the NEMO3 detector
After analysis of 5797 h of data from the detector NEMO3, new limits on
neutrinoless double beta decay of Mo-100 (T_{1/2} > 3.1 10^{23} y, 90% CL) and
Se-82 (T_{1/2} > 1.4 10^{23} y, 90% CL) have been obtained. The corresponding
limits on the effective majorana neutrino mass are: m < (0.8-1.2) eV and m <
(1.5-3.1) eV, respectively. Also the limits on double-beta decay with Majoron
emission are: T_{1/2} > 1.4 10^{22} y (90% CL) for Mo-100 and T_{1/2}> 1.2
10^{22} y (90%CL) for Se-82. Corresponding bounds on the Majoron-neutrino
coupling constant are g < (0.5-0.9) 10^{-4} and < (0.7-1.6) 10^{-4}.
Two-neutrino 2b-decay half-lives have been measured with a high accuracy,
T_{1/2} Mo-100 = [7.68 +- 0.02(stat) +- 0.54(syst) ] 10^{18} y and T_{1/2}
Se-82 = [10.3 +- 0.3(stat) +- 0.7(syst) ] 10^{19} y.Comment: 5 pages, 4 figure
Possible background reductions in double beta decay experiments
The background induced by radioactive impurities of and
in the source of the double beta experiment NEMO-3 has been
investigated. New methods of data analysis which decrease the background from
the above mentioned contamination are identified. The techniques can also be
applied to other double beta decay experiments capable of measuring
independently the energies of the two electrons.Comment: 15 pages, 13 figures, accepted in the Nuclear Instruments and Methods
Stochastic and epistemic uncertainty propagation in LCA
Purpose: When performing uncertainty propagation, most LCA practitioners choose to represent uncertainties by single probability distributions and to propagate them using stochastic methods. However the selection of single probability distributions appears often arbitrary when faced with scarce information or expert judgement (epistemic uncertainty). Possibility theory has been developed over the last decades to address this problem. The objective of this study is to present a methodology that combines probability and possibility theories to represent stochastic and epistemic uncertainties in a consistent manner and apply it to LCA. A case study is used to show the uncertainty propagation performed with the proposed method and compare it to propagation performed using probability and possibility theories alone. Methods: Basic knowledge on the probability theory is first recalled, followed by a detailed description of hal-00811827, version 1- 11 Apr 2013 epistemic uncertainty representation using fuzzy intervals. The propagation methods used are the Monte Carlo analysis for probability distribution and an optimisation on alpha-cuts for fuzzy intervals. The proposed method (noted IRS) generalizes the process of random sampling to probability distributions as well as fuzzy intervals, thus making the simultaneous use of both representations possible
Prevalence of Physical Frailty: Results from the DO-HEALTH Study
Background: Frailty is a geriatric syndrome associated with multiple negative health outcomes. However, its prevalence varies by population and instrument used. We investigated frailty and pre-frailty prevalence by 5 instruments in community-dwelling older adults enrolled to a randomized-controlled trial in 5 European countries. METHODS: Cross-sectional baseline analysis in 2,144 DO-HEALTH participants recruited from Switzerland, Austria, France, Germany, and Portugal with complete data for frailty. Frailty status was assessed by the Physical Frailty Phenotype [PFP], SOF-Frailty Index [SOF-FI], FRAIL-Scale, SHARE-Frailty Instrument [SHARE-FI], and a modified SHARE-FI, and compared by country, age, and gender. Logistic regression was used to determine relevant factors associated with frailty and pre-frailty. RESULTS: Mean age was 74.9 (±4.4) years, 61.6% were women. Based on the PFP, overall frailty and pre-frailty prevalence was 3.0% and 43.0%. By country, frailty prevalence was highest in Portugal (13.7%) and lowest in Austria (0%), and pre-frailty prevalence was highest in Portugal (57.3%) and lowest in Germany (37.1%). By instrument and overall, frailty and pre-frailty prevalence was highest based on SHARE-FI (7.0% / 43.7%) and lowest based on SOF-FI (1.0% / 25.9%). Frailty associated factors were residing in Coimbra (Portugal) [OR 12.0, CI 5.30-27.21], age above 75 years [OR 2.0, CI 1.17-3.45], and female gender [OR 2.8, CI 1.48-5.44]. The same three factors predicted pre-frailty. CONCLUSIONS: Among relatively healthy adults age 70 and older enroled to DO-HEALTH, prevalence of frailty and pre-frailty differed significantly by instrument, country, gender, and age. Among instruments, the highest prevalence of frailty and pre-frailty was documented by the SHARE-FI and the lowest by the SOF-FI
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