The quest for comparability: Calibration 2000

 Most efforts in quality control have been focussed on the reduction of intralaboratory variation and the assessment of interlaboratory variation. Over the last few years, the importance of bias in interlaboratory variation and intralaboratory shifts has become clear. Small shifts can sometimes have a large impact on the number of treated patients, particularly in assays where cut off values are used. For example in cholesterol, HDL-cholesterol, HbA1c and TSH assays. There is an obvious need for adequate calibration material. However, the process of development of international primary reference materials and reference methods takes time, and even if reference materials exist and are used by in vitro diagnostics manufacturers, there still remains significant and clinically relevant interlaboratory variance and intralaboratory shifts, as is seen, e.g. in protein chemistry. The harmonization of inter laboratory and intralaboratory results needs an impulse from professional organizations to convince individual laboratories of the importance and significance of bias. This applies to all subdisciplines of laboratory medicine. On the occasion of the 25th anniversary of the Foundation for External Quality Assessment (SKZL), a large interdisciplinary harmonization project called Calibration 2000 was launched in The Netherlands The strategy and first results are reported in this paper. The project aims at harmonization of laboratory data of several disciplines, using secondary calibration materials, leading to common reference ranges throughout The Netherlands. Received: 15 April 2000 · Accepted: 15 April 2000     

K Ratio H-Point Standard Additions Method

Abstract

A modification of H-point standard additions method is proposed in order to obtain an unbiased analyte concentration when both analyte and interferent are present in a sample. The method is called “K ratio H-point standard additions method.” The method uses the analytical signal data at two selected wavelengths and the K ratio of an interferent determined by using the method proposed by Ni Yongnian et al. at the same wavelengths, giving two straight lines that have a common point H with coordinates (-C_H, A_H), where C_H is the unknown analyte concentration and A_H is the absorbance of an interferent at one of the two selected wavelengths, which depends on the calculating method of K ratio. Examples of application of the proposed method are given.     

Measurement of uncertainty in peptide molecular weight determination using size-exclusion chromatography with multi-angle laser light-scattering detection and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

The molecular weight of biopolymers such as peptides or proteins is vital information for understanding their physical/chemical properties. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and size-exclusion chromotography-multi-angle laser light scattering (SEC-MALLS) techniques each with its advantages and limitations were used for molecular weight determination of the SPf66 peptide. The precision of each method was studied using a two-factor fully-nested design with all the analyses performed by the same operator on a single instrument. The overall precision corresponded to the time-different intermediate precision (i.e. time and repeatability conditions). In the case of SEC-MALLS, all potential uncertainty components were carefully evaluated in an Ishikawa diagram, then included and mathematically combined with the uncertainty arising from the accuracy assessment to provide the overall uncertainty. In this case, the refractive-index increment with solute concentration value (dn/dc) provided the most significant contribution to the combined uncertainty. A method for its quantitation is proposed. The accuracy of method B (SEC-MALLS) against reference method A (MALDI-TOF-MS) was assessed using the interval testing hypothesis to limit the risk of unacceptable bias. The results indicate that the bias of B is higher than the limit established at 5%, and is therefore not traceable to A under the studied conditions.     

The bias of k-step M-estimators

It is well-known that k-step M-estimators can yield a high efficiency without losing the breakdown point of the initial estimator. In this note we derive their bias curves. In the location framework the bias increases only slightly with k, but in the scale case the bias curves change considerably.     

The effects of time constraints on phonatory stability in normally speaking adult women

Forty normally speaking women sustained /a/ five times in two conditions,untimed and timed. In the untimed condition, phonation began whenever the subject felt ready. The timed task required subjects to begin phonation as quickly as possible after the examiner's signal. Conditions were counterbalanced across subjects. Jitter and shimmer values were obtained on a Kay Elemetrics Computerized Speech Lab (Pine Brook, NJ). Three distinct patterns of change emerged for fitter and shimmer from the untimed to the timed condition, reflecting either decreases, increases, or no change in values. These changes in jitter and shimmer values across conditions are related to a reaction time model of “bias toward accuracy.”     

Limits of detection and decision. Part 3

It has been shown that the MARLAP (Multi-Agency Radiological Laboratory Analytical Protocols) for estimating the Currie detection limit, which is based on ‘critical values of the non-centrality parameter of the non-central t distribution’, is intrinsically biased, even if no calibration curve or regression is used. This completed the refutation of the method, begun in Part 2. With the field cleared of obstructions, the true theory underlying Currie's limits of decision, detection and quantification, as they apply in a simple linear chemical measurement system (CMS) having heteroscedastic, Gaussian measurement noise and using weighted least squares (WLS) processing, was then derived. Extensive Monte Carlo simulations were performed, on 900 million independent calibration curves, for linear, “hockey stick” and quadratic noise precision models (NPMs). With errorless NPM parameters, all the simulation results were found to be in excellent agreement with the derived theoretical expressions. Even with as much as 30% noise on all of the relevant NPM parameters, the worst absolute errors in rates of false positives and false negatives, was only 0.3%.     

Programming configurational changes in systems of functionalised polymers using reversible intramolecular linkages

ABSTRACT

We study polymers functionalised by complexes forming intramolecular linkages. Simulations of chains forming reversible linkages are difficult due to entropic barriers that hamper the sampling of different connectivity states specified by the list of pairs of reacted complexes. We address this problem by devising Monte Carlo (MC) moves that change the connectivity state of the system by regrowing parts of the chain while simultaneously reacting bond-forming complexes. Along with moves that link/unlink pairs of complexes, we develop two types of bond-exchange moves. We use these algorithms to study self-assembly of single chain polymeric nanoparticles. When considering monofunctional precursors, we find branched and linear nanoparticle morphologies dominated by long and short intramolecular loops, respectively, along with hierarchical structures in which complexes belonging to different loops are cross-linked. In the strong association limit, equilibrium structures are only reached when using bond-exchange MC moves. We also consider bifunctional precursors in which two different types of complexes decorate the two halves of the chain. We find different types of morphologies featuring different amounts of linkages between complexes of different types. Such findings corroborate our method as a valuable tool to design and predict self-assembly of functional polymers.     

Single-mode fiber gyroscope with three depolarizers

In this letter we present a single-mode fiber gyroscope (FOG) with low long-term drift. Only single-mode fiber components except for three fiber depolarizers were used. A simplified mathematic model has been proposed to explain the bias stability of the gyro. Several open-loop and closed-loop FOGs with 0.1–0.5°/h drift have been demonstrated.     

Estimating the intensity of a cyclic Poisson process in the presence of linear trend

We construct and investigate a consistent kernel-type nonparametric estimator of the intensity function of a cyclic Poisson process in the presence of linear trend. It is assumed that only a single realization of the Poisson process is observed in a bounded window. We prove that the proposed estimator is consistent when the size of the window indefinitely expands. The asymptotic bias, variance, and the mean-squared error of the proposed estimator are also computed. A simulation study shows that the first order asymptotic approximations to the bias and variance of the estimator are not accurate enough. Second order terms for bias and variance were derived in order to be able to predict the numerical results in the simulation. Bias reduction of our estimator is also proposed.     

Marginal productivity index policies for scheduling a multiclass delay-/loss-sensitive queue

This paper addresses the problem of scheduling a Markovian multiclass queue with a finite dedicated buffer for each class, where class-dependent linear holding and rejection cost rates model differing levels of tolerance to delay and loss. The goal is to design well-grounded and tractable scheduling policies that nearly minimize expected total discounted or long-run average cost. New dynamic index policies are introduced, awarding higher priority to classes with larger index values, where a class’ index measures the marginal productivity of work at its current state. The results are obtained by deploying the work-cost analysis approach to marginal productivity indices (MPIs) for restless bandits developed by the author, which is extended to the bias criterion. The MPI furnishes new insights: for a loss-sensitive class, it is a decreasing function of the number of empty buffer spaces, independent of the buffer size; for a delay-sensitive class, it is a decreasing function of the queue length. Such opposite orderings show that preventive work is more valuable than reactive work for the latter classes, whereas the opposite holds for the former. The results of a computational study on two-class instances are reported, shedding light on how the MPI policy’s relative performance varies with each parameter. Parameter ranges are thus identified where the MPI policy is near optimal, and substantially outperforms conventional benchmark policies. 2000 Mathematics Subject Classification 90B22 · 90B36 · 90B18 · 60K25 · 60K30 · 68M20