Measurement Imprecision Research Articles

Effect of gravimetric correction and type of pipettes used in sample preparation on the precision of LC–MS/MS-based analyses

BackgroundCurrently, manual pipetting of human sample material is still a key process in sample preparation for chromatographic and mass spectrometric analyses in the clinical laboratory. In most cases, however, pipettes used in clinical laboratories are only specified for handling water-like liquids. Actual pipetted liquid volumes can be verified by weighing within the sample preparation process, and the results can be corrected accordingly (gravimetric correction). The aim of our study was to evaluate and compare the effects of gravimetric correction in terms of accuracy and precision for an air cushion and direct replacement pipette. MethodsForty-fold serial determination of linezolid in a spiked serum sample by ID-LC-MS/MS was applied as an exemplary measurement procedure. Polypropylene tubes were weighed before the addition of 50 µL serum, after the addition, and after the addition of the internal standard solution. Coefficients of variation (CV) were calculated as an indicator of measurement precision. ResultsThe use of a direct replacement pipette was associated with improved measurement imprecision than an air cushion pipette (CV 1.70% vs 2.49% for serum, uncorrected results). The results obtained after gravimetric correction showed improved precision with the use of an air cushion pipette compared to the conventional approach (CV 1.51% vs 1.61%). Using a direct replacement pipette, the impact of gravimetric correction on imprecision was negligible. ConclusionUsing direct replacement pipettes in sample preparation enables more precise ID-LC–MS/MS analyses than using air cushion pipettes. Gravimetric correction can be a useful tool to improve the precision of LC–MS/MS measurement procedures when complex matrices such as human serum are handled with commonly used air cushion pipettes.

Use of Telemedicine for the Physical Examination of Children With Fetal Alcohol Spectrum Disorders.

The fetal alcohol spectrum disorders (FASD) are among the most prevalent causes of neurodevelopmental disorders. The diagnosis is based on assessment of prenatal alcohol exposure, specific physical features identified with a dysmorphology examination, and neurobehavioral assessment. Prompt diagnosis of affected children is necessary to provide early intervention services in a timely manner; however, the availability of diagnostic expertise is limited. We propose telemedicine (TM) as a valid and reliable mode by which the physical phenotype of FASD can be accurately assessed. We compared face-to-face (F2F) physical examinations of the 3 key facial features and the resulting physical phenotype of the fetal alcohol syndrome (FAS) and partial FAS (pFAS), as well as 12 additional physical features seen more frequently in children with FAS than in the general population in 61 individuals with 2 different TM methods. These included a Transportable Examination Station system using a precision camera and a laptop and a Zoom secure connection system (ZOOM), using a smart phone and a tablet. We measured the percentages of agreement and the Cohen's K coefficient for each comparison. Agreements for most physical features and for the physical phenotype of FAS and pFAS were in the "almost perfect" range with some exceptions in the "substantial" range. Imprecision in measurement and subjectivity underlie lower agreement for some features, both F2F and using TM. We identified the optimal conditions for the F2F examinations in order to assure reliability using TM. TM is a valid and reliable method for the examination of the physical features of FAS that may contribute to greater access to an early diagnosis of FASD in children prenatally exposed to alcohol and/or with characteristic neurobehavioral deficits.

Phase-coherent sensing of the center-of-mass motion of trapped-ion crystals.

Trapped ions are sensitive detectors of weak forces and electric fields that excite ion motion. Here measurements of the center-of-mass motion of a trapped-ion crystal that are phase coherent with an applied weak external force are reported. These experiments are conducted far from the trap motional frequency on a two-dimensional trapped-ion crystal of approximately 100 ions, and determine the fundamental measurement imprecision of our protocol free from noise associated with the center-of-mass mode. The driven sinusoidal displacement of the crystal is detected by coupling the ion crystal motion to the internal spin degree of freedom of the ions using an oscillating spin-dependent optical dipole force. The resulting induced spin precession is proportional to the displacement amplitude of the crystal, and is measured with near-projection-noise-limited resolution. A 49 pm displacement is detected with a signal-to-noise ratio of 1 in a single experimental determination, which is an order-of-magnitude improvement over prior phase-incoherent experiments. This displacement amplitude is 40 times smaller than the zero-point fluctuations. With our repetition rate, an displacement sensitivity is achieved, which implies and sensitivities to forces and electric fields, respectively. This displacement sensitivity, when applied on-resonance with the center-of-mass mode, indicates the possibility of weak force and electric field detection below 10-3 yN/ion and 1 nV/m, respectively.

An experimental exploration of the properties of random frequency response functions

The vibro-acoustic analysis of complex structures over a broadband frequency range is an extremely challenging problem that may often require the use of a hybrid deterministic-statistical approach. Due to manufacturing imperfections, the frequency response functions (FRFs) of an ensemble of nominally identical systems can be considered to be random. These FRFs, however, have statistical properties that can be potentially used in vibro-acoustic models. This work explores some of these fundamental properties by using measured FRFs from an ensemble of nominally identical structures, obtained by randomising a thin rectangular plate using point masses. It is first shown that the measured ensemble of FRFs satisfies the analyticity-ergodicity condition, experimentally verifying this recently demonstrated fundamental property. Then, the ensemble is used to explore whether the direct field dynamic stiffness, a key parameter in a well-established hybrid deterministic-statistical formulation, can be obtained experimentally. The results are compared against those computed using numerical techniques, showing that measured data may be a suitable alternative provided that an ensemble of systems can be measured. Finally, an alternative method, based on the use of virtual point masses, opposed to physical ones, is proposed for those cases where experimental randomisation is particularly challenging. It has been found, however, that the method may be extremely sensitive to measurement imprecisions, specially when applied to lightly damped structures. It is concluded that the statistical properties of random causal FRFs are not only interesting in themselves, but can enhance and extend vibro-acoustic prediction models.

Does emphasizing management bias decrease auditors’ sensitivity to measurement imprecision?

Both management bias and measurement imprecision threaten the accurate reporting of complex accounting estimates, yet audit policymakers and practitioners often place a strong emphasis on bias. I examine whether directing auditors’ attention towards management bias can come at the expense of insufficient auditor sensitivity to measurement imprecision, potentially threatening overall audit quality. My primary investigation, Study 1, finds that when managers’ explicit incentives to bias financial reports are relatively weaker, an imbalanced emphasis on bias causes auditor-like participants in a stylized setting to “lower their guard” to a greater extent than when environmental factors place a more balanced emphasis on bias and imprecision. Study 2 indicates that an imbalanced emphasis on imprecision does not similarly distract auditors from bias. Study 3 utilizes a more contextually rich setting and demonstrates that an imbalanced emphasis on bias prompts even professional auditors to neglect imprecision. Accordingly, this paper suggests that a balanced emphasis on both management bias and measurement imprecision can mitigate negative consequences of auditors focusing on the former and neglecting the latter.

Some geometrical properties of fission-track-surface intersections in apatite

Abstract Parallel fission-track-surface intersections identify the grains in an etched apatite mount that have been polished parallel to their prism faces and mark the orientations of their c-axes. Their lengths (Dpar) are a practical kinetic parameter that is indicative of the track annealing rate of apatite. Little is known, however, about their geometrical properties in non-prism faces. We present a model calculation of the frequency distributions of the orientations, lengths, and widths of track-surface intersections in non-prism faces. The current model does not include the effects of surface etching or measurement imprecision. However, as far as it goes, it is consistent with measurements in apatite surfaces up to 30° to the c-axis. Regardless of the model, we submit that the statistical properties of the fission-track-surface intersections have practical uses. The distribution of their orientations is characteristic of the orientation of the etched surface relative to the c-axis. The distribution of their lengths presents a possible tool for investigating track etching, in particular for evaluating the tracks added and lost through surface etching. The distribution of their widths is a potential kinetic parameter independent of surface orientation and less susceptible to the factors, such as the sampling method and surface etch rate, that produce conflicting Dpar values.

P03 Preparing glucose infusions in neonatal intensive care: does it matter which method is used?

AimsAdministering intravenous (IV) glucose is common on the Neonatal Intensive Care Unit. Bedside preparation of glucose solutions is often necessary, usually through addition of concentrated 50% glucose to a commercially available bag. Accuracy in the glucose concentration of locally prepared bags will be influenced by a number of factors: variable overages in IV fluid bags, method of preparation and imprecision of measurement during preparation. We aimed to assess the accuracy of three different methods of preparation which had been identified through a national survey.MethodsBags of 12.5%, 15% and 25% glucose were manufactured through the addition of 50% glucose solution to commercially available bags of 10% or 20% glucose. Three bags of each concentration, were manufactured by each of the methods below:Removal of fluid from base bag prior to addition of 50% glucose, taking into account published overage.Removal of fluid from base bag prior to addition of 50% glucose, not taking into account published overage.Addition of 50% glucose, without prior removal of fluid from base bag.Three 5 mL samples were then taken from each prepared bag and sent for analysis. Glucose concentration was measured using a quantitative spectrophotometric method. As a control, three 5 mL samples were taken from three bags each of commercially available 5%, 10% and 20% glucose infusion solutions and assayed as above.ResultsA total of 81 ‘test’ samples were sent for analysis along with 27 control samples. One 20% glucose control sample was lost in transport meaning that 80 samples were analysed. The median result for each concentration and method was calculated. For method a) where the intended final glucose concentration was 12.5%, 15% and 25%, the actual concentrations obtained were 11.2%, 13.3% and 22.9% respectively. For method b) where the intended final glucose concentration was 12.5%, 15% and 25%, the actual concentrations obtained were 12.4%, 13.4% and 22.0% respectively. For method c) where the intended final glucose concentration was 12.5%, 15% and 25%, the actual concentrations obtained were 12.1%, 13.8% and 20.3% respectively. For the 5%, 10% and 20% control solutions the median reported glucose concentrations were 5.1%, 10.3% and 19.9% respectively.ConclusionsIrrespective of method used and the intended strength, the measured glucose concentration was lower than that being aimed for. In some cases, the glucose concentration was only 80% of that intended. It is not possible to conclude that one method is superior in terms of accuracy. Although it might be possible from our results to suggest the most accurate method for each concentration, this is unlikely to be predictable as manufacturers quote overages as a range rather than an absolute value. In clinical practice, preparation of a glucose solution with a lower concentration than that expected may result in prolonged hypoglycaemia with potential neurological sequelae. An alternative to bedside manufacture of glucose infusion solutions is needed. This could include pharmacy compounding of glucose strengths not commercially available or ‘piggy-backing’ of 50% glucose onto an infusion of a commercially available strength, ideally supported by a glucose load calculator.

Construction of a top-loading adiabatic calorimeter equipped with a refrigerator

A top-loading type adiabatic calorimeter equipped with a refrigerator, which functions in the temperature range of 20–300 K, is developed. Since the refrigerator is built in, measurements can be conducted without replenishing liquid nitrogen or liquid helium; this, in addition to the top-loading type calorimeter features, reduces the time required to set the sample by 10 min. The heat capacity of benzoic acid, used as a standard sample for heat capacity measurement, is measured to evaluate the device performance. The heat capacity measurement imprecisions were ±0.8 % at 20–50 K, ± 0.3 % at 50–130 K, and ±0.2 % at above 130 K. The inaccuracies of the heat capacity from the benzoic acid measurement results were ±1.1 % at 20–100 K and ±0.9 % at 100–300 K. These performance results are the same for any traditional adiabatic calorimeter considering the heat capacity ratio between the sample and the cell. Using this device, the molecular-weight dependence of the heat capacity of the styrene oligomer in the solid state is measured and the effect of the end groups on the heat capacity is investigated. It is suggested that the influence of the end group on the heat capacity disappeared rapidly as the molecular weight increased.

Experimental Demonstration of Robust Quantum Steering

We analyze and experimentally demonstrate quantum steering using criteria based on generalized entropies and criteria with minimal assumptions based on the so-called dimension-bounded steering. Further, we investigate and compare their robustness against experimental imperfections such as misalignment in the shared measurement reference frame. While entropy based criteria are robust against imperfections in state preparation, we demonstrate an advantage in dimension-bounded steering in the presence of measurement imprecision. As steering with such minimal assumptions is easier to reach than fully nonlocal correlations, and as our setting requires very little trust in the measurement devices, the results provide a candidate for the costly Bell tests while remaining highly device independent.

Salecker–Wigner–Karolyhazy Gedankenexperiment in light of the self-gravity

In Gedankenexperiment mentioned in the title, the imprecision in space-time measurement is related to the spreading of clock's wave-function with the passage of time required for the measurement. Special relativity puts a bound on the measurement time, it cannot be reduced arbitrarily as the signal used for the measurement cannot propagate with speed greater than that of light. In view of this reasoning, one is led to conclude that the clock should be heavy enough to slow down its wave-function from spreading with time. However, the general relativity puts an upper bound on clock's mass, since its size must remain greater then the Schwarzschild radius associated to it. This way one reaches a limit in length measurement. However, as is discussed below, an additional insight into the question comes by taking into account self-gravitational effects. As a result, the uncertainty in length measurement is reduced to the Planck length.

Image-Based Neonatal Hyperbilirubinemia Screening after Hospital Discharge

Background: Newborn infants who are risk for severe hyperbilirubinemia and cared at home should be monitored for progression of jaundice. We aimed to verify if a smart phone application (BiliScan Inc), which uses automated imaging for bilirubin (AIB), can be used to estimate total serum bilirubin (TSB) levels at home. Methods: A convenience sample of 1038 “healthy” infants in China were prospectively enrolled to a singlecenter study in 2016. Correlations between AIB and TcB measurements were correlated to TB measurements. Bias and imprecision of AIB measurements were determined using Bland-Altman analysis. The diagnostic value of AIB was compared by the area-under-curve (AUC) values of receiver operator characteristic (ROC) curves. Results: The best correlation and AUC for AIB were at the sternum, both with values of 0.76. We truncated performances to 369 TB values >5 and <15 mg/dL, and sternal AIB showed the best correlation to TB (r =0.5, P<0.0001). The AUC for this range was 0.54. However, from a subset of 200 AIB values >13.5 mg/dL (n=369 babies), the sensitivity and negative predictive value (NPV) were 100% with a specificity of 50%. Furthermore, Bland-Altman analyses showed a bias and imprecision of AIB and TcB when TB was >13.5 and <15 mg/dL. Conclusion: The use of AIB may be a potentially useful screening device for neonatal jaundice. Its performance requires additional improvements for accurate measurements across wider ranges of TB levels.

In-Situ Determination of Buildings’ Thermo-Physical Characteristics

Accurate determination of building’s critical thermo-physical characteristics such as the walls’ thermal resistance, thermal conductivity, and volumetric heat capacity is essential to indicate effective and efficient energy conservation strategies at building level. In practice, the values of these parameters, which determine not only possible energy savings, but also related costs, are rarely available because the current determination methods are time-and-effort-expensive, and consequently seldom used. This thesis combines theories, simulations, computations, and experiments to develop and improve methods and approaches for determination of a number of buildings’ most important thermophysical characteristics. First, a modification to the existing standard method, “ISO 9869 Average Method” is proposed to measure the walls’ thermal resistance. Two current problems are solved: long measurement duration (weeks) and imprecision. To further shorten the measurement period to a few hours, a new transient in-situ method, Excitation Pulse Method, EPM (Patent No. 2014467), is then developed and tested. This method allows the determination of the walls’ response factors which can be applied directly in dynamic models. More importantly, it is used to extract critical construction information including walls’ thermal resistance, thermal conductivity, volumetric heat capacity, and the possible layer composition. Finally, in an attempt to reduce the hassle, cost, and intrusion associated with locally-conducted experiments, the use of data from smart meters and home automation systems is explored. Building’s global characteristics including heat loss coefficient, global heat capacitance and daily air change rates are accordingly determined.

Averaging of results derived from different, simultaneously acquired mass transitions in ID-LC-MS/MS – Potential impact on measurement imprecision

BackgroundLC–MS/MS allows for many measurands monitoring different mass transitions simultaneously. So far, such alternative mass transitions are usually assessed as “quantifier and qualifier ions” in order to rule out interferences in individual samples. However, quantification can also be based on assessment of alternative mass transitions for both the measurand and its internal standard, with two distinct results for one injection of an individual sample. These paired results can be averaged. The aim of this study was to determine the potential impact of this averaging approach on measurement imprecision. MethodsWe studied the impact of averaging results from different transitions for four exemplary measurands (linezolid (LIN), piperacillin (PIP), voriconazole (VOR), ethylglucuronide (ETG)). Intra-batch studies were performed with 21 injections of single clinical samples in sequence for each analyte (LIN, PIP, VOR), and a between-batch study with evaluation of data from routine QC samples from 20 series over 20 weeks (ETG). CVs and their confidence intervals were assessed comparatively for quantification based on single transitions, and for averaged results from these two transitions, respectively. ResultsIn all data sets, we observed lower CVs for the averaged results compared to the results obtained from single mass transitions. CVs from averaged results were up to 39.4% lower compared to the CVs observed for results obtained from single transitions for the respective measurands. ConclusionAveraging of quantification results obtained from separate mass transitions acquired simultaneously in ID-LC-MS/MS seems to have the potential to minimize the measurement imprecision for different measurands in short- and long-term settings.

Oral galactagogues (natural therapies or drugs) for increasing breast milk production in mothers of non-hospitalised term infants.

Oral galactagogues (natural therapies or drugs) for increasing breast milk production in mothers of non-hospitalised term infants.

Inter-Laboratory Agreement of Insulin-like Growth Factor 1 Concentrations Measured Intact by Mass Spectrometry

Insulin-like growth factor-I (IGF-1) is measured mainly by immunoassay for the diagnosis and treatment of growth hormone (GH) disorders, and to detect misuse of GH in sport. Immunoassays often have insufficient inter-laboratory agreement, especially between commercial kits. Over the expected range of IGF-1 in blood (∼50-500 ng/mL), in an inter-laboratory study we previously established a measurement imprecision of 11% (%CV) for the digested protein analyzed by LC-MS. Measuring intact IGF-1 by LC-MS should be simpler. However, no inter-laboratory agreement has been published. Intact and trypsin-digested IGF-1 in 32 serum samples from healthy volunteers and human growth hormone administration studies were analyzed by LC-MS using different instruments in five laboratories, as well as by immunoassay in a single laboratory. Another 100 samples were analyzed for IGF-1, both intact and after trypsin-digestion, in each laboratory by LC-MS. The statistical relationship between measurements and the imprecision of each assay group was assessed. An intra-laboratory variability of 2-4% CV was obtained. Inter-laboratory variability was greater at 14.5% CV. Orthogonal regression of intact versus trypsin-digestion methods (n = 646) gave a slope of 1.01 and intercept of 2.05 ng/mL. LC-MS measurements of IGF-1 by intact and trypsin-digestion methods are not statistically different and each is similar to immunoassay. The two LC-MS approaches may be used interchangeably or together to eliminate concerns regarding an immunoassay IGF-1 measurement. Because intact and digested IGF-1 measurements generally agreed within 20% of each other, we propose this as a criterion of assay acceptability.

Evaluation of the new Beckman Coulter Access hsTnI: 99th percentile upper reference limits according to age and sex in the Korean population

BackgroundDefining the 99th percentile upper reference limits (URL) of cardiac troponin I (cTnI) is critical because it is clinically important in determining myocardial injury, and is variable among reagents, age, sex, or races. The analytical performance of the new, high- sensitivity reagent Beckman Coulter Access hsTnI was evaluated, and its 99th percentile URL was determined in the Korean population. MethodsAnalytical performances of Access hsTnI assay were evaluated including imprecision and limit of measurements. To define the reference limits, 600 healthy subjects were included with similar proportions of sex and age groups. ResultsBeckman Coulter Access hsTnI assay presented a limit of blank, detection, and quantitation at 10% CV of 0.32 ng/L, 0.63 ng/L, and 6.1 ng/L, respectively, and 98.3% of the healthy population showed cTnI above the limit of detection. The 99th percentile URLs were 9.5 ng/L (90% CI 7.4–14.9), 7.8 ng/L (90% CI 5.5–19.2 ng/L), and 11.3 ng/L (90% CI 8.0–15.7 ng/L) in 600 healthy participants, 300 women and 300 men, respectively with imprecision less than 10% CV. The median values and 99th percentile URLs of hsTnI were higher in men and the age group ≥50 years than in women and the age group <50 years, respectively. ConclusionsAccess hsTnI assay met the performance criteria of the IFCC for high-sensitivity cTnI assays. Their 99th percentile URLs in the Korean population were lower than the manufacturer’s claims. cTnI values were significantly different among different sex and age groups.

Spatial Flow-Field Approximation Using Few Thermodynamic Measurements—Part II: Uncertainty Assessments

AbstractIn this second part of our two-part paper, we provide a detailed, frequentist framework for propagating uncertainties within our multivariate linear least squares model. This permits us to quantify the impact of uncertainties in thermodynamic measurements—arising from calibrations and the data acquisition system—and the correlations therein, along with uncertainties in probe positions. We show how the former has a much larger effect (relatively) than uncertainties in probe placement. We use this non-deterministic framework to demonstrate why the well-worn metric for assessing spatial sampling uncertainty falls short of providing an accurate characterization of the effect of a few spatial measurements. In other words, it does not accurately describe the uncertainty associated with sampling a non-uniform pattern with a few circumferentially scattered rakes. To this end, we argue that our data-centric framework can offer a more rigorous characterization of this uncertainty. Our paper proposes two new uncertainty metrics: one for characterizing spatial sampling uncertainty and another for capturing the impact of measurement imprecision in individual probes. These metrics are rigorously derived in our paper and their ease in computation permits them to be widely adopted by the turbomachinery community for carrying out uncertainty assessments.

Repeatability imprecision from analysis of duplicates of patient samples and control materials

Measurement imprecision is usually calculated from measurement results of the same stabilized control material(s) obtained over time, and is therefore, principally, only valid at the concentration(s) of the selected control material(s). The resulting uncertainty has been obtained under reproducibility conditions and corresponds to the conventional analytical goals. Furthermore, the commutability of the control materials used determines whether the imprecision calculated from the control materials reflects the imprecision of measuring patient samples. Imprecision estimated by measurements of patient samples uses fully commutable samples, freely available in the laboratories. It is commonly performed by calculating the results of routine patient samples measured twice each. Since the duplicates are usually analysed throughout the entire concentration interval of the patient samples processed in the laboratory, the result will be a weighted average of the repeatability imprecision measured in the chosen measurement intervals or throughout the entire interval of concentrations encountered in patient care. In contrast, the uncertainty derived from many measurements of control materials over periods of weeks is usually made under reproducibility conditions. Consequently, the repeatability and reproducibility imprecision play different roles in the inference of results in clinical medicine. The purpose of the present review is to detail the properties of the imprecision calculated by duplicates of natural samples, to explain how it differs from imprecision calculated from single concentrations of control materials, and to elucidate what precautions need to be taken in case of bias, e.g. due to carry-over effects.

Virtual synchronous machines with fast current loop

Virtual synchronous machines (VSM) are inverters that behave towards the power grid like synchronous generators. One popular way to realize such inverters are synchronverters, whose control algorithm has evolved over time, but both theoretical analysis and practical observations show that the output currents of a synchronverter are very sensitive to grid voltage measurement errors and processing delay, as well imprecisions in the PWM process. To overcome this problem (of excessive sensitivity), we propose in this paper to use a different type of control to realize a VSM, that includes a fast current controller as the internal control loop of the inverter. Our simulations and experiments show that this results in a dramatic reduction of the sensitivity of the VSM to various kinds of measurement errors, noise and imprecision, and hence to the proper operation of such inverters. In particular, it leads to a large reduction of the total harmonic distortion of the grid currents.

Does Emphasizing Management Bias Decrease Auditors’ Sensitivity to Measurement Imprecision?

Does Emphasizing Management Bias Decrease Auditors’ Sensitivity to Measurement Imprecision?