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 ± standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 ± 3 years, 17 ± 6.2 kg, and 118 ± 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 ± SD) for piperacillin and tazobactam were as follows: clearance, 0.22 ± 0.07 and 0.19 ± 0.07 liter/h/kg, respectively; volume of distribution, 0.43 ± 0.16 and 0.37 ± 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]

The Grizzly, February 14, 1986

Eckman Speaks on Corporate Takeovers • Students to Lose Booze? • Alcohol Restrictions Plague Neighboring Campuses • Campus Memo: Get and Stay Involved • Proposal Raises Serious Questions • Students Speak Out On Alcohol • Profile: Dr. Fago • Editorial: Drug Use Could Fill Vacuum • Letters: UC. Should Get Out of the Business; Alpha Chi Sigma Needs Support; Sauna Controversy Heats up; Fire Alarms are not Toys!; False Alarm Jeopardized Safety • Nursing Homes Part III: MCGRC\u27s Sordid Past • Bears Face Widener in the Big Game • Racich Praises Grapplers • Lady Swimmers Top Susquehanna • Women\u27s B-ball Finale • Confident \u27Mers\u27 Win Again • Track Records Set at Delaware • Heather Camp: Swimming\u27s Leading Lady • Forum: Human Rights in Latin America • Wenhold Awarded for Service • Ursinus in California • U.S. Trade Policy • A Peek at U.C.\u27s Favorite TVhttps://digitalcommons.ursinus.edu/grizzlynews/1157/thumbnail.jp

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 “recognize patterns” 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 “staying in patches”. 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

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 ± 1.6 mg/kg) of cefuroxime was administered before surgical incision, and a second dose (mean, 14.4 ± 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 priori–Bayesian 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) μg/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 post–dose-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

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