Acceptable Measurement Uncertainty Research Articles

Non-contact temperature control and stereo digital image correlation for high-temperature testing of miniature tubular specimens.

Component failures very often occur due to high temperature and multiaxial stress states arising at critical component locations. To imitate such loading conditions, a multiaxial miniature testing system (MMTS) with axial, torsional, and internal pressurization capabilities for high-temperature testing of miniature tubular specimens has been developed. Among many challenges of developing the MMTS, uniform heating, temperature measurement and control, and surface strain measurement on a miniature tubular specimen at high temperatures have significant difficulties. This paper addresses two significant challenges: first, the development of a non-contact temperature control system using infrared thermography to uniformly heat a miniature specimen of 1 mm outer diameter (OD), and second, the development of a stereo digital image correlation (stereo-DIC) setup for strain measurement on the miniature specimen subjected to high temperature. The developed control system maintains the test temperature through a closed feedback loop and employs a fail-safe mechanism to protect the MMTS load frame components against unanticipated temperature rises. The thermocouple wire-size effect on the measured temperature was examined for three different wire sizes: 0.05, 0.25, and 0.5 mm for accurate emissivity determination required for infrared thermography. Emissivities of the specimen surface at different high temperatures were experimentally determined. Inherent error analysis of the developed high-temperature stereo-DIC setup showed acceptable strain measurement uncertainty. The effectiveness of the developed non-contact temperature control system and high-temperature stereo-DIC setup has been verified by performing tensile testing of a 1 mm OD specimen at 500 °C.

Optical fibre based real-time measurements during an LDR prostate brachytherapy implant simulation: using a 3D printed anthropomorphic phantom

An optical fibre sensor based on radioluminescence, using the scintillation material terbium doped gadolinium oxysulphide (Gd2O2S:Tb) is evaluated, using a 3D printed anthropomorphic phantom for applications in low dose-rate (LDR) prostate brachytherapy. The scintillation material is embedded in a 700 µm diameter cavity within a 1 mm plastic optical fibre that is fixed within a brachytherapy needle. The high spatial resolution dosimeter is used to measure the dose contribution from Iodine-125 (I-125) seeds. Initially, the effects of sterilisation on the sensors (1) repeatability, (2) response as a function of angle, and (3) response as a function of distance, are evaluated in a custom polymethyl methacrylate phantom. Results obtained in this study demonstrate that the output response of the sensor, pre- and post-sterilisation are within the acceptable measurement uncertainty ranging from a maximum standard deviation of 4.7% pre and 5.5% post respectively, indicating that the low temperature sterilisation process does not damage the sensor or reduce performance. Subsequently, an LDR brachytherapy plan reconstructed using the VariSeed treatment planning system, in an anthropomorphic 3D printed training phantom, was used to assess the suitability of the sensor for applications in LDR brachytherapy. This phantom was printed based on patient anatomy, with the volume and dimensions of the prostate designed to represent that of the patient. I-125 brachytherapy seeds, with an average activity of 0.410 mCi, were implanted into the prostate phantom under trans-rectal ultrasound guidance; following the same techniques as employed in clinical practice by an experienced radiation oncologist. This work has demonstrated that this sensor is capable of accurately identifying when radioactive I-125 sources are introduced into the prostate via a brachytherapy needle.

Blowing Kinetics, Pressure Resistance, Thermal Stability, and Relaxation of the Amorphous Phase of the PET Container in the SBM Process with Hot and Cold Mold. Part II: Statistical Analysis and Interpretation of Tests.

The technology of filling drinks without preservatives (such as fresh juices, iced tea drinks, and vitaminized drinks) is carried out using hot filling. Mainly due to the production costs and lower carbon footprint, polyethylene terephthalate (PET) bottles are increasingly used in this technology. In this paper, the main aim is to describe and interpret the results of statistical analysis of the influence of the temperature of the blow mold in the SBM (stretch blow molding) process and the method of hot filling on the macroscopic and microscopic bottle properties. The macroscopic bottle properties were defined by the thickness profile, pressure resistance, thermal stability, and the coefficients of blowing kinetics. In addition, the influence of the SBM process on the microscopic PET material properties (in the bottle) relative to the microscopic preform properties was analyzed. The microscopic properties were defined by the degree of crystallite, density, and relaxation of the amorphous phase of the PET material. For this purpose, response surface experiments were performed for the two analyzed factors, i.e., the temperature of the blow mold and the method of hot filling. The sample size was investigated to determine the minimum number of repetitions (number of bottles in the measurement series) required to achieve acceptable measurement uncertainty. The research conducted shows that, despite fulfilling the postulate of acceptable measurement uncertainty, in terms of the power of ANOVA (analysis of variance) in DOE (design of experiment), the accepted number of bottles in the measurement series is too small. The tests of the bottle material density, material crystallite, and relaxation of amorphous phase relative to the preform material density, material crystallite, and relaxation of amorphous phase show that microcavity effects occur during the deformation of the PET material, and that these are associated with the orientation of the microstructure. The blow kinetics study shows that there is a gradient of flow of the bottle material over the thickness of the bottle wall during blowing, and it has been deduced that the air temperature between the blow mold and the wall of the blown bottle has an impact on the kinetics of blowing the bottle.

Blowing Kinetics, Pressure Resistance, Thermal Stability, and Relaxation of the Amorphous Phase of the PET Container in the SBM Process with Hot and Cold Mold. Part I: Research Methodology and Results.

The technology of filling drinks without preservatives (such as fresh juices, iced tea drinks, vitaminized drinks) is carried out using hot filling. Mainly due to the production costs and lower carbon footprint, polyethylene terephthalate bottles, commonly called PET, are increasingly used in this technology. In this paper, the main aim is to describe the statistical analysis methodology of the influence of the temperature of the blow mold in the SBM process and the method of hot filling on the macroscopic and microscopic bottle properties. The macroscopic bottle properties were defined by the thickness profile, pressure resistance, thermal stability, and the coefficients of blowing kinetics. Moreover, the influence of the SBM (stretch blow moulding) process on the microscopic PET material properties (in the bottle) relative to the microscopic preform properties was analyzed. The microscopic properties were defined by the degree of crystallite, density, and relaxation of the amorphous phase of the PET material. For this purpose, response surface experiments were performed for the two analyzed factors (independent variables), i.e., the temperature of the blow mold and the method of hot filling. The sample size was investigated to determine the minimum number of repetitions (number of bottles in the measurement series) required to achieve acceptable measurement uncertainty. The research conducted shows that despite fulfilling the postulate of acceptable measurement uncertainty, in terms of the power of ANOVA (analysis of variance) in DOE (design of experiment) the accepted number of bottles in the measurement series is too small. The tests of the bottle material density, material crystallite, and relaxation of amorphous phase relative to the preform material density, material crystallite, and relaxation of amorphous phase show that the microcavity effects occur during the deformation of the PET material, and that these are associated with the orientation of the microstructure. The blow kinetics study shows that there is a gradient of flow of the bottle material over the thickness of the bottle wall during blowing, and it has been deduced that the air temperature between the blow mold and the wall of the blown bottle has an impact on the kinetics of blowing the bottle.

Exact analytical solution to ultrasonic interfacial reflection enabling optimal oil film thickness measurement

The ultrasonic reflection from a lubricated interface has been widely analyzed to measure fluid film thickness, with different algorithms being applied to overcome measurement accuracy and resolution issues. Existing algorithms use either the amplitude or the phase angle of the ultrasonic interfacial reflection. In this paper, a new algorithm (named the “exact model – complex”) that simultaneously utilizes both the amplitude and the phase of the complex ultrasonic reflection coefficient is proposed and mathematically derived. General procedures for theoretical analysis in terms of measurement accuracy and uncertainty are proposed and applied to the new algorithm, the beneficial features of which (as compared to other existing algorithms) can be summarized as: 1) a direct calculation, instead of an iterative approximation, 2) guaranteed maximum measurement accuracy, and 3) acceptable measurement uncertainty. None of the existing methods have showed this combination of benefits. Moreover, two groups of raw data from previous experimental studies are utilized to further validate the practical feasibility of the new algorithm. Overall, the proposed “exact model – complex” algorithm fully exploits the potential of ultrasonic reflection for oil film thickness measurement, with an accurate and a convenient calculation suited to practical implementation.

The internal quality control in the traceability era.

To be accurate and equivalent, laboratory results should be traceable to higher-order references. Furthermore, their quality should fulfill acceptable measurement uncertainty (MU) as defined to fit the intended clinical use. With this aim, in vitro diagnostics (IVD) manufacturers should define a calibration hierarchy to assign traceable values to their system calibrators. Medical laboratories should know and verify how manufacturers have implemented the traceability of their calibrators and estimate the corresponding MU on clinical samples. Accordingly, the internal quality control (IQC) program should be redesigned to permit IVD traceability surveillance through the verification by medical laboratories that control materials, provided by the manufacturer as a part of measuring systems, are in the clinically suitable validation range (IQC component I). Separately, laboratories should also monitor the reliability of employed IVD measuring systems through the IQC component II, devoted to estimation of MU due to random effects and to obtaining MU of provided results, in order to apply prompt corrective actions if the performance is worsening when compared to appropriate analytical specifications, thus jeopardizing the clinical validity of test results.

Traceability validation of six enzyme measurements on the Abbott Alinity c analytical system.

Background Laboratory professionals should independently verify the correct implementation of metrological traceability of commercial measuring systems and determine if their performance is fit for purpose. We evaluated the trueness, uncertainty of measurements, and transferability of six clinically important enzyme measurements (alanine aminotransferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], creatine kinase [CK], γ-glutamyltransferase [γGT], and lactate dehydrogenase [LDH]) performed on the Abbott Alinity c analytical system. Methods Target values and associated uncertainties were assigned to three pools for each enzyme by using the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference measurement procedures (RMPs) and the pools were then measured on the Alinity system. Bias estimation and regression studies were performed, and the uncertainty associated with Alinity measurements was also estimated, using analytical performance specifications (APS) derived from biological variability of measurands as goals. Finally, to validate the transferability of the obtained results, a comparison study between two Alinity systems located in Milan, Italy, and Bydgoszcz, Poland, was carried out. Results Correct implementation of traceability to the IFCC RMPs and acceptable measurement uncertainty fulfilling desirable (ALP, AST, LDH) or optimal APS (ALT, CK, γGT) was verified for all evaluated enzymes. An optimal alignment between the two Alinity systems located in Milan and Bydgoszcz was also found for all enzyme measurements. Conclusions We confirmed that measurements of ALT, ALP, AST, CK, γGT, and LDH performed on the Alinity c analytical system are correctly standardized to the IFCC reference measurement systems and the system alignment is consistent between different platforms.

Rising above helium: A hydrogen carrier gas chromatography flame ionization detection (GC-FID) method for the simultaneous quantification of toxic alcohols and ethylene glycol in human plasma specimens

Here we validate a GC, Flame Ionization Detection (GC-FID), liquid injection method using hydrogen as a carrier gas combining analysis of toxic volatile alcohols (VA): methanol, ethanol, isopropanol, acetone, as well as glycols, ethylene glycol (EG) and propylene glycol (PG), in a single method. Methodology200 μL of calibrator, QC, or patient specimen were deproteinized with 400 μL of acetonitrile containing internal standards (10 mmol/L N-propyl alcohol for VA and 2.5 mmol/L 1,2-butanediol for glycols). GC-FID analysis using hydrogen carrier gas and nitrogen makeup gas utilized an Agilent 7890 system equipped with Agilent 7683 liquid autosampler on a 30 m × 530 μm RTX-200 fused silica column. Method validation included repeatability, recovery, carryover, linearity, lower limit of quantification (LLOQ), accuracy, selectivity and measurement uncertainty. ResultsThe 8.3 min from injection to injection reduced time of analysis by 45% over a previously reported method using Helium carrier gas with no loss in resolution. Within-run and Between-run variability were ≤1.4% and ≤6.8% respectively. Recovery was 100% within a 95% confidence interval. Carryover was negligible for all but EG. LLOQ was <1 mmol/L for all analytes. The upper range of linearity was 120 mmol/L for methanol, ethanol and isopropanol, 100 mmol/L for acetone and 50 mmol/L for EG. Analytes demonstrated acceptable accuracy and measurement uncertainty using College of American Pathologists (CAP) criteria. Toluene can cause a false positive EG, while benzene, xylene and 1,3 butanediol can cause false negative EG. ConclusionsConverting from Helium to Hydrogen carrier gas benefits patient care through a reduction in turnaround time and provides a cost savings to the laboratory.

Optimizing Sampling Parameters of CMM Data Acquisition for Machining Error Correction of Freeform Surfaces

Abstract An optimization study using the design of experiment technique is described, in which the surface profile height of a freeform surface, determined in coordinate measurements, is the response variable. The control factors are coordinate sampling parameters, i.e. the sampling grid size and the measuring tip diameter. As a result of the research, an optimal combination of these parameters was found for surface mapping with acceptable measurement uncertainty. The presented study is the first stage of optimization of machining error correction for the freeform surface and was intended to take into account mechanical-geometric filtration of surface irregularities caused by these geometrical parameters. The tests were carried out on a freeform workpiece milled with specific machining parameters, Ra of the surface roughness was 1.62 μm. The search for the optimal combination of parameters was conducted using Statistica software.

Experiences from RILEM TC 235-CTC in recommending a test method for chloride threshold values in concrete

Chloride threshold value is an important input parameter in service life predictions. There has been a need for a reliable method for testing this value in order to improve the understanding of basic factors influencing the corrosion initiation. For this reason RILEM technical committee (TC) 235-CTC was formed with the ultimate aim to recommend a suitable test method capable of delivering data with acceptable measurement uncertainty. During the TC’s life, a test method was proposed and a Round-Robin Test (RRT) was organised to evaluate it. Due to the unexpected results from the RRT, the ultimate aim of the TC was not reached. There were some experiences obtained from the TC’s work especially in designing the test method which are worthy for supporting future researchers continuing to search for a reliable test method for it. This technical letter presents the TC’s experiences.

Inter-laboratory validation of the starch digestibility method for determination of rapidly digestible and slowly digestible starch

The digestibility of starch in foods, which is influenced by the ingredients, formulation and preparation conditions, is a major determinant of glycaemic response. The terms rapidly digestible starch (RDS) and slowly digestible starch (SDS) along with the associated analytical methodology were developed by Englyst to characterise this nutritionally relevant food attribute. The measurement uncertainty of this starch digestibility method is evaluated here with an inter-laboratory trial. Six laboratories took part in the study testing ten cereal products with mean (range) contents of RDS: 48.4 g/100 g, (23.4–76·9) and, SDS: 10.9 g/100 g, (0.8–24.2). Based on the repeatability and reproducibility measurements, the calculated uncertainty was 3.6 g/100 g for RDS and 1.9 g/100 g for SDS. This trial has demonstrated acceptable measurement uncertainty and confirmed the transferability of the method between laboratories. The SDS content can identify foods rich in slow release carbohydrates with their associated health benefits.

A method for predicting thermal waves in dual-phase-lag heat conduction

We predict whether thermal waves exist or not in dual-phase-lag heat conduction by measuring the time lag ratio (τq/τT). In this method, a one-dimensional model of cylindrical heating is developed and solved by the method of Laplace transform. The time lag ratio is then derived from the time derivative of the square of excess temperature on the heater wall in the initial heating stage. Experimentally, we also applied this method to measure the time lag ratios for sand and lean pork, both of which are less than 1 within acceptable measurement uncertainty, indicating no thermal waves generated. This method is of great importance for the application of dual-phase-lag heat conduction model since it can predict existence of thermal waves through a simple experiment.

Progress and impact of enzyme measurement standardization.

International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has established reference measurement procedures (RMPs) for the most popular enzymes. Manufacturers should assign values to commercial calibrators traceable to these RMPs to achieve equivalent results in clinical samples, independent of reagent kits, instruments, and laboratory where the measurement is carried out. The situation is, however, far from acceptable. Some manufacturers continue to market assays giving results that are not traceable to internationally accepted RMPs. Meanwhile, end-users often do not abandon assays with demonstrated insufficient quality. Of the enzyme measurements, creatine kinase (CK) is satisfactorily standardized and a substantial improvement in performance of marketed γ-glutamyltranspeptidase (GGT) assays has been demonstrated. Conversely, aminotransferase measurements often exceed the desirable analytical performance because of the lack of pyridoxal-5-phosphate addition in the commercial reagents. Measurements of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and α-amylase (AMY) still show major disagreement, suggesting the need for improvement in implementing traceability to higher-order references. This is mainly the result of using assays with different analytical selectivities for these enzymes. The definition by laboratory professionals of the clinically acceptable measurement uncertainty for each enzyme together with the adoption by EQAS of commutable materials and use of an evaluation approach based on trueness represent the way forward for reaching standardization in clinical enzymology.

Shutter-less calibration of uncooled infrared cameras

Abstract. Infrared (IR) cameras based on microbolometer focal plane arrays (FPAs) are the most widely used cameras in thermography. New fields of applications like handheld devices and small distributed sensors benefit from the latest sensor improvements in terms of cost and size reduction. In order to compensate for disturbing influences derived from changing ambient conditions, radiometric cameras use an optical shutter for online recalibration purposes, partially also together with sensor temperature stabilization. For these new applications, IR cameras should consist only of infrared optics, a sensor array, and digital signal processing (DSP). For acceptable measurement uncertainty values without using an optical shutter (shutter-less), the disturbing influences of changing thermal conditions have to be treated based on temperature measurements of the camera interior. We propose a compensation approach based on calibration measurements under controlled ambient conditions. All correction parameters are determined during the calibration process. Without sensor temperature stabilization (TEC-less), the pixel responsivity is also affected by the camera temperature changes and has to be considered separately. This paper presents the details of the compensation procedure and discusses relevant aspects to gain low temperature measurement uncertainty. The residual measurement uncertainty values are compared to the shutter-based compensation approach.

Role and Responsibilities of Laboratory Medicine Specialists in the Verification of Metrological Traceability of in Vitro Medical Diagnostics / Uloga I Odgovornosti Specijalista Laboratorijske Medicine U Verifikaciji Metrološke Sledljivosti In Vitro Medicinske Dijagnostike

SummaryTo be accurate and equivalent, laboratory results should be traceable to higher-order references. Furthermore, their quality should fulfill acceptable measurement uncertainty as defined to fit the intended clinical use. With this aim, in vitro diagnostics (IVD) manufacturers should define a calibration hierarchy to assign traceable values to their system calibrators and to fulfill during this process uncertainty limits for calibrators, which should represent a proportion of the uncertainty budget allowed for clinical laboratory results. It is therefore important that, on one hand, the laboratory profession clearly defines the clinically acceptable uncertainty for relevant tests and, on the other hand, end-users may know and verify how manufacturers have implemented the traceability of their calibrators and estimated the corresponding uncertainty. Important tools for IVD traceability surveillance are quality control programmes through the daily verification by clinical laboratories that control materials of analytical systems are in the manufacturer’s declared validation range [Internal Quality Control (IQC) component I] and the organization of External Quality Assessment Schemes meeting metrological criteria. In a separate way, clinical laboratories should also monitor the reliability of employed commercial systems through the IQC component II, devoted to estimation of the measurement uncertainty due to random effects, which includes analytical system imprecision together with individual laboratory performance in terms of variability.

Diffusion-controlled toluene reference material for VOC emissions testing: International interlaboratory study

The measurement of volatile organic compound (VOC) emissions from building products and materials by manufacturers and testing laboratories, and the use of the test results for labeling programs, continue to expand. One issue that hinders wide acceptance for chamber product testing is the lack of a reference material to validate test chamber performance. To meet this need, the National Institute of Standards and Technology (NIST) and Virginia Tech (VT) have developed a prototype reference material that emits a single VOC similar to the emissions of a diffusion-controlled building product source with a dynamic emissions profile. The prototype material has undergone extensive testing at NIST and a pilot interlaboratory study (ILS) with four laboratories. The next development step is an evaluation of the prototype source in multiple-sized chambers of 14 laboratories in seven countries. Each laboratory was provided duplicate specimens and a test protocol. Study results identified significant issues related to the need to store the source at a subzero Celsius temperature until tested and possible inconsistencies in large chambers. For laboratories using a small chamber and meeting all the test method criteria, the results were very encouraging with relative standard deviations ranging from 5% to 10% across the laboratories.Implications: Currently, the chamber performance of laboratories conducting product VOC emissions testing is assessed through interlaboratory studies (ILS) using a source with an unknown emission rate. As a result, laboratory proficiency can only be based on the mean and standard deviation of emission rates measured by the participating ILS laboratories. A reference material with a known emission rate has the potential to provide an independent assessment of laboratory performance as well as improve the quality of interlaboratory studies. Several international laboratories with different chamber testing systems demonstrated the ability to measure the emission rate of such a reference material within an acceptable measurement uncertainty.

Verification of in vitro medical diagnostics (IVD) metrological traceability: Responsibilities and strategies

To be accurate and equivalent, laboratory results should be traceable to higher-order references. Furthermore, their analytical performance should fulfill acceptable measurement uncertainty criteria defined to fit the intended clinical use. With this aim, In Vitro Diagnostics (IVD) manufacturers should define a calibration hierarchy to assign traceable values to their system calibrators and to fulfill during this process uncertainty limits for calibrators, which should represent a proportion of the uncertainty budget allowed for laboratory results. It is important that end-users may know and verify how manufacturers have implemented the traceability of their calibrators and estimated the corresponding uncertainty. However, full information about traceability and combined uncertainty of calibrators is currently not available. Important tools for IVD traceability surveillance are the verification by laboratories of the consistency of declared performance during daily operations performed in accordance with the manufacturer's instructions and the organization of appropriately structured External Quality Assessment (EQA) programs. The former activity should be accomplished by analyzing system control materials and confirming that current measurements are in the manufacturer's established control range. With regard to EQA, it is mandatory that target values for materials are assigned with reference procedures by accredited laboratories, that materials are commutable and that a clinically allowable inaccuracy for participant's results is defined.

Application of Multiple Line Integrated Spectroscopy on CO Concentration Measurement

The paper presents possibility of application multiple of integrated spectroscopy for measuring CO concentration in a gas mixture. Sensors that are based on the method discussed can be applied in analyses of gas mixtures inside a power boiler or products of biomass gasification process. The principles of the method has been presented, however the main attention was paid to proper selection of the wavelength range and thus optoelectronic components. It would limit influence of disturbance factors and on the other hand, enable higher dynamic range of the CO analyser. Both simulation and laboratory tests that were presented in the paper would enable to build CO analyser that could operate in industrial conditions at acceptable measurement uncertainty. DOI: http://dx.doi.org/10.5755/j01.eee.19.9.5648

A Review of Selected Inorganic Surface Water Quality-Monitoring Practices: Are We Really Measuring What We Think, and If So, Are We Doing It Right?

Successful environmental/water quality-monitoring programs usually require a balance between analytical capabilities, the collection and preservation of representative samples, and available financial/personnel resources. Due to current economic conditions, monitoring programs are under increasing pressure to do more with less. Hence, a review of current sampling and analytical methodologies, and some of the underlying assumptions that form the bases for these programs seems appropriate, to see if they are achieving their intended objectives within acceptable error limits and/or measurement uncertainty, in a cost-effective manner. That evaluation appears to indicate that several common sampling/processing/analytical procedures (e.g., dip (point) samples/measurements, nitrogen determinations, total recoverable analytical procedures) are generating biased or nonrepresentative data, and that some of the underlying assumptions relative to current programs, such as calendar-based sampling and stationarity are no longer defensible. The extensive use of statistical models as well as surrogates (e.g., turbidity) also needs to be re-examined because the hydrologic interrelationships that support their use tend to be dynamic rather than static. As a result, a number of monitoring programs may need redesigning, some sampling and analytical procedures may need to be updated, and model/surrogate interrelationships may require recalibration.

Numerical experimental validation of a GM-FDTD code for the study of cellular phones

This paper presents a numerical–experimental validation of a finite-difference time-domain code employing a graded-mesh (GM-FDTD). To this aim, a prototype of a mobile phone (mock-up), equipped with a helical antenna, is manufactured and modelled using the GM-FDTD code and a freeware code based on the method of moments (MoM). The return loss (RL), together with the near electric- and magnetic-field distributions, have been computed using the GM-FDTD code and compared with the MoM results and measurements. Moreover, the specific absorption rate (SAR) induced by the phone inside a cubic phantom has been measured and evaluated with the GM-FDTD code. The agreement between the numerical and experimental results is within acceptable measurement uncertainty. © 2005 Wiley Periodicals, Inc. Microwave Opt Technol Lett 47: 396–400, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.21180