3D Particle Tracking Velocimetry Method: Advances and Error Analysis

A full three-dimensional particle tracking system was developed and tested. By using three separate CCDs placed at the vertices of an equilateral triangle, the threedimensional location of particles can be determined. Particle locations measured at two different times can then be used to create a three-component, three-dimensional velocity field. Key developments are: the ability to accurately process overlapping particle images, offset CCDs to significantly improve effective resolution, allowance for dim particle images, and a hybrid particle tracking technique ideal for three-dimensional flows when only two sets of images exist. An in-depth theoretical error analysis was performed which gives the important sources of error and their effect on the overall system. This error analysis was verified through a series of experiments, which utilized a test target with 100 small dots per square inch. For displacements of 2.54mm the mean errors were less than 2% and the 90% confidence limits were less than 5.2 μm in the plane perpendicular to the camera axis, and 66 μm in the direction of the camera axis. The system was used for flow measurements around a delta wing at an angle of attack. These measurements show the successful implementation of the system for three-dimensional flow velocimetry

An Injector for the CLIC Test Facility (CTF3)

The CLIC Test Facility (CTF3) is an intermediate step to demonstrate the technical feasibility of the key concepts of the new RF power source for CLIC. CTF3 will use electron beams with an energy range adjustable from 170 MeV (3.5 A) to 380 MeV (with low current). The injector is based on a thermionic gun followed by a classical bunching system embedded in a long solenoidal field. As an alternative, an RF photo-injector is also being studied. The beam dynamics studies on how to reach the stringent beam parameters at the exit of the injector are presented. Simulations performed with the EGUN code showed that a current of 7 A can be obtained with an emittance less than 10 mm.mrad at the gun exit. PARMELA results are presented and compared to the requested beam performance at the injector exit. Sub-Harmonic Bunchers (SHB) are foreseen, to switch the phase of the bunch trains by 180 degrees from even to odd RF buckets. Specific issues of the thermionic gun and of the SHB with fast phase switch are discussed

Atomic-scale investigation of hydrogen distribution in a Ti–Mo alloy

Ingress of hydrogen is often linked to catastrophic failure of Ti-alloys. Here, we quantify the hydrogen distribution in fully β and α + β Ti–Mo alloys by using atom probe tomography. Hydrogen does not segregate at grain boundaries in the fully β sample but segregates at some α/β phase boundaries with a composition exceeding 20 at.% in the α + β sample. No stable hydrides were observed in either sample. The hydrogen concentration in β phases linearly decreases from ~13 at. % to ~4 at. % with increasing Mo-content, which is ascribed to the suppression of hydrogen uptake by Mo addition

Clinical applications of population pharmacokinetic models of antibiotics: Challenges and perspectives

Because of increasing antimicrobial resistance and the shortage of new antibiotics, there is a growing need to optimize the use of old and new antibiotics. Modelling of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of antibiotics can support the optimization of dosing regimens. Antimicrobial efficacy is determined by susceptibility of the drug to the microorganism and exposure to the drug, which relies on the PK and the dose. Population PK models describe relationships between patients characteristics and drug exposure. This article highlights three clinical applications of these models applied to antibiotics: 1) dosing evaluation of old antibiotics, 2) setting clinical breakpoints and 3) dosing individualization using therapeutic drug monitoring (TDM). For each clinical application, challenges regarding interpretation are discussed. An important challenge is to improve the understanding of the interpretation of modelling results for good implementation of the dosing recommendations, clinical breakpoints and TDM advices. Therefore, also background information on PK/PD principles and approaches to analyse PK/PD data are provided

Comparison of pharmacodynamics of azithromycin and erythromycin in vitro and in vivo

In this study, we determined the efficacy of various dosing regimens for erythromycin and azithromycin against four pneumococci with different susceptibilities to penicillin in an in vitro pharmacokinetic model and in a mouse peritonitis model. The MIC was 0.03 microg/ml, and the 50% effective doses (determined after one dose) of both drugs were comparable for the four pneumococcal strains and were in the range of 1.83 to 6.22 mg/kg. Dosing experiments with mice, using regimens for azithromycin of one to eight doses/6 h, showed the one-dose regimen to give the best result; of the pharmacodynamic parameters tested (the maximum drug concentration in serum [Cmax], the times that the drug concentration in serum remained above the MIC and above the concentration required for maximum killing, and the area under the concentration time curve), Cmax was the best predictor of outcome. The bacterial counts in mouse blood or peritoneal fluid during the first 24 h after challenge were not correlated to survival of the mice. The serum concentration profiles obtained with mice for the different dosing regimens were simulated in the in vitro pharmacokinetic model. Here as well, the one-dose regimen of azithromycin showed the best result. However, the killing curves in vivo in mouse blood and peritoneal fluid and in the vitro pharmacokinetic model were not similar. The in vitro killing curves showed a decrease of 2 log10 within 2 and 3 h for azithromycin and erythromycin, respectively whereas the in vivo killing curves showed a bacteriostatic effect for both drugs. It is concluded that the results in terms of predictive pharmacodynamic parameters are comparable for the in vitro and in vivo models and that high initial concentrations of azithromycin favor a good outcome