400 research outputs found
Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children
The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillintazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (TMIC) of\u3e50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean Âą standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 Âą 3 years, 17 Âą 6.2 kg, and 118 Âą 41 ml/min/1.73m2, respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean Âą SD) for piperacillin and tazobactam were as follows: clearance, 0.22 Âą 0.07 and 0.19 Âą 0.07 liter/h/kg, respectively; volume of distribution, 0.43 Âą 0.16 and 0.37 Âą 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of\u3e90% at MICs of/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of\u3e90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of\u3e80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children
Pharmacokinetics of Cefuroxime are not Significantly Altered by Cardiopulmonary Bypass in Children
Poster presented at: SPA/AAP PEDIATRIC ANESTHESIOLOGY 2010 - Winter Meeting; April 2010; San Antonio, TX
Modeling the source of GW150914 with targeted numerical-relativity simulations
In fall of 2015, the two LIGO detectors measured the gravitational wave
signal GW150914, which originated from a pair of merging black holes. In the
final 0.2 seconds (about 8 gravitational-wave cycles) before the amplitude
reached its maximum, the observed signal swept up in amplitude and frequency,
from 35 Hz to 150 Hz. The theoretical gravitational-wave signal for merging
black holes, as predicted by general relativity, can be computed only by full
numerical relativity, because analytic approximations fail near the time of
merger. Moreover, the nearly-equal masses, moderate spins, and small number of
orbits of GW150914 are especially straightforward and efficient to simulate
with modern numerical-relativity codes. In this paper, we report the modeling
of GW150914 with numerical-relativity simulations, using black-hole masses and
spins consistent with those inferred from LIGO's measurement. In particular, we
employ two independent numerical-relativity codes that use completely different
analytical and numerical methods to model the same merging black holes and to
compute the emitted gravitational waveform; we find excellent agreement between
the waveforms produced by the two independent codes. These results demonstrate
the validity, impact, and potential of current and future studies using
rapid-response, targeted numerical-relativity simulations for better
understanding gravitational-wave observations.Comment: 11 pages, 3 figures, submitted to Classical and Quantum Gravit
Anomalous Fluctuations of Directed Polymers in Random Media
A systematic analysis of large scale fluctuations in the low temperature
pinned phase of a directed polymer in a random potential is described. These
fluctuations come from rare regions with nearly degenerate ``ground states''.
The probability distribution of their sizes is found to have a power law tail.
The rare regions in the tail dominate much of the physics. The analysis
presented here takes advantage of the mapping to the noisy-Burgers' equation.
It complements a phenomenological description of glassy phases based on a
scaling picture of droplet excitations and a recent variational approach with
``broken replica symmetry''. It is argued that the power law distribution of
large thermally active excitations is a consequence of the continuous
statistical ``tilt'' symmetry of the directed polymer, the breaking of which
gives rise to the large active excitations in a manner analogous to the
appearance of Goldstone modes in pure systems with a broken continuous
symmetry.Comment: 59 pages including 8 figures ( REVTEX 3.0 )E-mail:
[email protected]
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Acceleration of relativistic beams using laser-generated terahertz pulses
Dielectric structures driven by laser-generated terahertz (THz) pulses may
hold the key to overcoming the technological limitations of conventional
particle accelerators and with recent experimental demonstrations of
acceleration, compression and streaking of low-energy (sub-100 keV) electron
beams, operation at relativistic beam energies is now essential to realize the
full potential of THz-driven structures. We present the first THz-driven linear
acceleration of relativistic 35 MeV electron bunches, exploiting the collinear
excitation of a dielectric-lined waveguide driven by the longitudinal electric
field component of polarization-tailored, narrowband THz pulses. Our results
pave the way to unprecedented control over relativistic electron beams,
providing bunch compression for ultrafast electron diffraction, energy
manipulation for bunch diagnostics, and ultimately delivering high-field
gradients for compact THz-driven particle acceleration.Comment: 8 pages, 4 figure
Local Orientation and the Evolution of Foraging: Changes in Decision Making Can Eliminate Evolutionary Trade-offs
Information processing is a major aspect of the evolution of animal behavior. In foraging, responsiveness to local feeding opportunities can generate patterns of behavior which reflect or ârecognize patternsâ in the environment beyond the perception of individuals. Theory on the evolution of behavior generally neglects such opportunity-based adaptation. Using a spatial individual-based model we study the role of opportunity-based adaptation in the evolution of foraging, and how it depends on local decision making. We compare two model variants which differ in the individual decision making that can evolve (restricted and extended model), and study the evolution of simple foraging behavior in environments where food is distributed either uniformly or in patches. We find that opportunity-based adaptation and the pattern recognition it generates, plays an important role in foraging success, particularly in patchy environments where one of the main challenges is âstaying in patchesâ. In the restricted model this is achieved by genetic adaptation of move and search behavior, in light of a trade-off on within- and between-patch behavior. In the extended model this trade-off does not arise because decision making capabilities allow for differentiated behavioral patterns. As a consequence, it becomes possible for properties of movement to be specialized for detection of patches with more food, a larger scale information processing not present in the restricted model. Our results show that changes in decision making abilities can alter what kinds of pattern recognition are possible, eliminate an evolutionary trade-off and change the adaptive landscape
Error-analysis and comparison to analytical models of numerical waveforms produced by the NRAR Collaboration
The Numerical-Relativity-Analytical-Relativity (NRAR) collaboration is a
joint effort between members of the numerical relativity, analytical relativity
and gravitational-wave data analysis communities. The goal of the NRAR
collaboration is to produce numerical-relativity simulations of compact
binaries and use them to develop accurate analytical templates for the
LIGO/Virgo Collaboration to use in detecting gravitational-wave signals and
extracting astrophysical information from them. We describe the results of the
first stage of the NRAR project, which focused on producing an initial set of
numerical waveforms from binary black holes with moderate mass ratios and
spins, as well as one non-spinning binary configuration which has a mass ratio
of 10. All of the numerical waveforms are analysed in a uniform and consistent
manner, with numerical errors evaluated using an analysis code created by
members of the NRAR collaboration. We compare previously-calibrated,
non-precessing analytical waveforms, notably the effective-one-body (EOB) and
phenomenological template families, to the newly-produced numerical waveforms.
We find that when the binary's total mass is ~100-200 solar masses, current EOB
and phenomenological models of spinning, non-precessing binary waveforms have
overlaps above 99% (for advanced LIGO) with all of the non-precessing-binary
numerical waveforms with mass ratios <= 4, when maximizing over binary
parameters. This implies that the loss of event rate due to modelling error is
below 3%. Moreover, the non-spinning EOB waveforms previously calibrated to
five non-spinning waveforms with mass ratio smaller than 6 have overlaps above
99.7% with the numerical waveform with a mass ratio of 10, without even
maximizing on the binary parameters.Comment: 51 pages, 10 figures; published versio
Large N Expansion for 4-Epsilon Dimensional Oriented Manifolds in Random Media
The equilibrium statistical mechanics of a d dimensional ``oriented''
manifold in an N+d dimensional random medium are analyzed in d=4-epsilon
dimensions. For N=1, this problem describes an interface pinned by impurities.
For d=1, the model becomes identical to the directed polymer in a random
medium. Here, we generalize the functional renormalization group method used
previously to study the interface problem, and extract the behavior in the
double limit epsilon small and N large, finding non-analytic corrections in
1/N. For short-range disorder, the interface width scales as a power law of the
width. We calculate the roughness exponent characterizing this power law for
small epsilon and large N, as well as other properties of the phase. We also
analyze the behavior for disorder with long-range correlations, as is
appropriate for interfaces in random field systems, and study the crossover
between the two regimes.Comment: 23 pages + 4 figures available upon request, Plain Te
Cefuroxime Pharmacokinetics in Pediatric Cardiovascular Surgery Patients Undergoing Cardiopulmonary Bypass
Objectives The objective of this study was to determine the pharmacokinetics of cefuroxime in children undergoing cardiopulmonary bypass (CPB) for cardiovascular surgery. Design A prospective study. Setting A tertiary pediatric teaching hospital. Participants Infants and children undergoing CPB were enrolled in the study. Intervention An initial dose (mean, 24.2 Âą 1.6 mg/kg) of cefuroxime was administered before surgical incision, and a second dose (mean, 14.4 Âą 7.9 mg/kg) was administered in the CPB prime solution. Serial blood samples were obtained before, during, and after the CPB process. Samples were shipped on dry ice to the analytic laboratory and concentrations determined by a validated high-performance liquid chromatography method. A 2-compartment pharmacokinetic model was fitted to the data using maximum a prioriâBayesian estimation, with weight as a covariate. Monte Carlo simulations of a single-dose (25 mg/kg pre-CPB) approach and a 2-dose (25 mg/kg pre- and 12.5-mg/kg prime solution dose) approach were performed. Measurements and Main Results Fifteen subjects (9 males/6 females) were enrolled in the study, with median (range) age and weight of 11 (3-34) months and 9.5 (4.5-15.4) kg, respectively. The median (range) duration of CPB was 136 (71-243) minutes. Median and range cefuroxime pharmacokinetic parameters were as follows: maximum concentration (Cmax) dose, 1: 328 (150-512) Îźg/mL; systemic clearance, 0.050 (0.041-0.058) L/h/kg; steady-state volume of distribution, 0.213 (0.081-0.423) L/kg; volume of distribution in the central compartment, 0.081 (0.046-0.162) L/kg; and elimination half-life, 3.76 (1.03-6.81) hours. The median 8-hour postâdose-simulated cefuroxime concentrations were 26.5 and 16.0 mg/L for the 2-dose and single-dose regimens, respectively. Conclusion Manufacturers recommend that pediatric doses of cefuroxime (25-50 mg/kg) can be used in infants and children undergoing CPB to maintain adequate serum concentrations for surgical-site infection prophylaxis. A second intraoperative dose, administered through the CPB circuit, provides no additional prophylactic advantage
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