Using tolerance intervals in pre-study validation of analytical methods to predict in-study results. The fit-for-future-purpose concept

It is recognized that the purpose of validation of analytical methods is to demonstrate that the method is suited for its intended purpose. Validation is not only required by regulatory authorities, but is also a decisive phase before the routine use of the method. For a quantitative analytical method the objective is to quantify the target analytes with a known and suitable accuracy. For that purpose, first, a decision about the validity of the method based on prediction is proposed: a method is declared proper for routine application if it is considered that most of the future results generated will be accurate enough. This can be achieved by using the "beta-expectation tolerance interval" (accuracy profile) as the decision tool to assess the validity of the analytical method. Moreover, the concept of "fit-for-purpose" is also proposed here to select the most relevant response function as calibration curve, i.e. choosing a response function based solely on the predicted results this model will allow to obtain. This paper reports four case studies where the results obtained with quality control samples in routine were compared to predictions made in the validation phase. Predictions made using the "beta-expectation tolerance interval" are shown to be accurate and trustful for decision making. It is therefore suggested that an adequate way to conciliate both the objectives of the analytical method in routine analysis and those of the validation step consists in taking the decision about the validity of the analytical method based on prediction of the future results using the most appropriate response function curve, i.e. the fit-for-future-purpose concept.     

On the Robustness of ‘Insurance Type’ Spares Provisioning Strategies

‘Insurance type’ spares are spares for unique parts which are essential to the operation of the equipment in which they serve, and which have an appreciable probability of not needing replacement during the lifetime of the equipment. They require a stocking strategy which is dependent on time and the actual occurrence of failures. The values of parameters in even the simplest of models of the dynamic spares stocking decision problem are usually known with great uncertainty, if at all. For one such model the sensitivity of (near-)optimal strategies to variations in the parameter values is investigated.     

Magnetization Transfer Imaging of Rat Brain under Non-steady-state Conditions. Contrast Prediction Using a Binary Spin–Bath Model and a Super-Lorentzian Lineshape

Magnetization transfer contrast imaging using turbo spin echo and continuous wave off-resonance irradiation was carried out on rat brainin vivoat 4.7 T. By systematically varying the off-resonance irradiation power and the offset-frequency, the signal intensities obtained under steady-state for both transverse and longitudinal magnetization were successfully analyzed with a simple binary spin–bath model taking into account a free water compartment and a pool of protons with restricted motions bearing a super-Lorentzian lineshape. Due to important RF power deposition, such experimental conditions are not practical for routine imaging on humans. An extension of the model was derived to describe the system for shorter off-resonance pulse duration, i.e., when the longitudinal magnetization of the free protons has not reached a steady-state. Data sets obtained for three regions of interest, namely thecorpus callosum,the basal ganglia, and the temporal lobe, were correctly interpreted for off-resonance pulse durations varying from 0.3 to 3 s. The parameter sets obtained from the calculations made it possible to predict the contrast between the different regions as a function of the pulse power, the offset frequency, and pulse duration. Such an approach could be extended to contrast prediction for human brain at 1.5 T.     

Study of the vortex dynamics in single crystals of the high-T c superconductor Tl2Ba2CaCu2O8 via205Tl NMR

The²⁰⁵Tl linewidth in single crystals of the high-T _c superconductor Tl₂Ba₂CaCu₂O₈ (T _c≈105 K) is analyzed for the normal (N) and impurity (I) Tl-sites. On the I-sites Ca has been replaced by Tl. Measurements were performed in a field of 4.7 T. The normal state linewidth on the N and I sites is shown to be mainly determined by a distribution in Knight shifts. To simulate the final increase below 50 K we have studied the vortex lattice in a single superconducting sheet by a molecular dynamics method for systems up to 2000 vortices. The results compare well with the experimental data. This implies that the temperature dependence of the linewidth in this highly anisotropic material is determined by flux dynamics and only marginally by the temperature dependence of the penetration depth.     

Study on the applicability of instrumental measures for black-box evaluation of static feedback control in hearing aids

Presented is a report on black-box evaluation of feedback control systems for commercial hearing aids. The aim of the study is to examine the ability of existing instrumental measures to quantify the performance of the feedback control system in black-box settings and on realistic signals, when more than one element of the signal processing chain may be active (compression, noise suppression, microphone directionality, etc.). The evaluation is carried out on 6 different hearing aids and for 10 measures. Thereby it is possible to see which measure is best suited to measuring which specific characteristic of the feedback control system, and serves as a beginning for conducting perceptual tests. The study uses static (but variable) feedback paths and is based on signals recorded from the in-ear microphone of an artificial head, on which the hearing instruments are mounted.     

Horizontal localization with bilateral hearing aids: without is better than with

This paper studies the effect of bilateral hearing aids on directional hearing in the frontal horizontal plane. Localization tests evaluated bilateral hearing aid users using different stimuli and different noise scenarios. Normal hearing subjects were used as a reference. The main research questions raised in this paper are: (i) How do bilateral hearing aid users perform on a localization task, relative to normal hearing subjects? (ii) Do bilateral hearing aids preserve localization cues, and (iii) Is there an influence of state of the art noise reduction algorithms, more in particular an adaptive directional microphone configuration, on localization performance? The hearing aid users were tested without and with their hearing aids, using both a standard omnidirectional microphone configuration and an adaptive directional microphone configuration. The following main conclusions are drawn. (i) Bilateral hearing aid users perform worse than normal hearing subjects in a localization task, although more than one-half of the subjects reach normal hearing performance when tested unaided. For both groups, localization performance drops significantly when acoustical scenarios become more complex. (ii) Bilateral, i.e., independently operating hearing aids do not preserve localization cues. (iii) Overall, adaptive directional noise reduction can have an additional and significant negative impact on localization performance.