Measurement Imprecision Research Articles

Imprecision of Breslow thickness measurements in melanoma around AJCC staging cutoffs and their implications for patient management

Imprecision of Breslow thickness measurements in melanoma around AJCC staging cutoffs and their implications for patient management

Breslow Thickness Measurements of Melanomas Around American Joint Committee on Cancer Staging Cut-Off Points: Imprecision and Terminal Digit Bias Have Important Implications for Staging and Patient Management.

Breslow thickness is the most important prognostic factor in patients with clinically localized primary cutaneous melanomas, and its accuracy has important implications for staging and management. A review of the Melanoma Institute Australia database and population-based data for the state of New South Wales, Australia, found an unexpectedly large number of melanomas reported as being exactly 1.0mm thick. We sought to determine possible causes for this biologically implausible finding. The tumor thickness of 125 invasive cutaneous melanomas with a recorded Breslow thickness of 0.9-1.1mm was remeasured and recorded by two pathologists. Concordance of measurements between the two pathologists was high (intraclass correlation coefficient 0.816, 95% CI 0.733-0.873). The original measurements showed clustering at 0.9, 1.0, and 1.1mm, whereas the review measurements did not. The original measurements staged 84 cases (72%) as T1 and 33 (28%) as T2, while the reviewed measurements staged 58 cases (50%) as T1 and 59 (50%) as T2 (p<0.001). Our study demonstrated imprecision in Breslow thickness measurements and its significant impact on staging. Two potential sources of imprecision are failure to follow standardized thickness measurement guidelines and the phenomenon of terminal digit bias, not previously identified as a problem in this field. Educating pathologists about this phenomenon and the importance of utilizing ocular micrometers may improve the precision of melanoma thickness measurements around critical staging cut-off points. Clinicians must also be educated to appreciate that there is an inevitable margin of error with Breslow thickness measurements that should be considered when making management decisions.

Multianalyte Conventional Reference Material (MacRM): A Useful Tool for Nationwide Standardization of Laboratory Measurements for Medical Care-A Model Study in Japan.

The Japanese Committee for Clinical Laboratory Standards (JCCLS) has developed a multianalyte conventional reference material (MacRM) for nationwide standardization of laboratory measurements. To prepare the MacRM, pooled sera were obtained from healthy Japanese individuals. Target values of the pooled sera for 30 analytes were assigned on the basis of the measurement results of 45 certified clinical laboratories whose calibration was verified by measuring certified reference materials (CRMs) provided by the National Institute of Standards and Technology, the Institute for Reference Materials and Measurements, and JCCLS. Commutability of MacRM was assessed by comparison with results for 150 individual inpatients at Fukuoka University Chikushi Hospital. Survey samples were prepared by essentially the same method for MacRM but without target values. The survey samples were used to assess agreement among 165 laboratories that used various assay kits and platforms calibrated with the MacRM. The commutability of MacRM was confirmed for 30 analytes with sera from 150 individual patients. The imprecision (CV) of measurements of survey samples (high and low concentrations) among the 165 laboratories was 0.4%-10.0%. Twenty-six of 30 analytes were within the goals for interinstitutional allowable bias. An aliquot of MacRM stored frozen at -80 °C remained stable for ≥4 years. The MacRM was successfully applied as a calibrator to achieve nationwide standardization for 30 analytes measured by 165 laboratories that used various methods from different manufacturers.

Overwhelming Thermomechanical Motion with Microwave Radiation Pressure Shot Noise.

We measure the fundamental noise processes associated with a continuous linear position measurement of a micromechanical membrane incorporated in a microwave cavity optomechanical circuit. We observe the trade-off between the two fundamental sources of noise that enforce the standard quantum limit: the measurement imprecision and radiation pressure backaction from photon shot noise. We demonstrate that the quantum backaction of the measurement can overwhelm the intrinsic thermal motion by 24dB, entering a new regime for cavity optomechanical systems.

Descent of the fetal head (station) during the first stage of labor

High station at specific points in the first stage of labor, such as a floating head on admission, or at 4-cm dilation or when arrest of dilation occurs, is associated with higher rates of failure to deliver vaginally. Therefore it could be useful to know if station is within an expected range at a given dilation during first stage. Arrest of descent disorders have been defined thus far on criteria applicable in the second stage. Statistical modeling is an attractive methodology to characterize the relationship between station and dilation because the resulting mathematical expressions could be used as a reference for comparison in the future. In addition, they can be used to produce a finely graded assessment of descent using numerical terms such as percentile rankings. A 2-step approach to potentially improving the assessment of station could be to develop a statistical model that describes the general relationship between station and dilation in the first stage of uncomplicated births and then determine if such a model would have identified births with complications related to poor labor progress. Given the complex nature of labor data, especially the imprecision of dilation and station measurement, it is not immediately evident that such a model is identifiable or what its precision would be. We sought to characterize in mathematical terms the relationship of station to dilation during the first stage of labor for nulliparous and multiparous women with spontaneous vaginal births. This retrospective cohort study included 28,121 exams from 5555 women with singleton cephalic presentations at ≥37 weeks' gestation with electronic fetal monitoring tracings, who delivered vaginally without instrumentation and had 5-minute Apgar scores >6 at 2 academic community referral hospitals in 2012 through 2013. Women with a previous cesarean birth were excluded. We used longitudinal statistical techniques suitable to biological data that were irregularly sampled with repeated measures over time. A linear relationship was observed between station and dilation. For both nulliparous and multiparous women the final model was a linear regression with random effects for intercept and slope and a first-order autoregressive correlation structure. The 5th-95th range of station at any given dilation spanned about 3-4 cm. Our results demonstrate a general trend of increasing descent of the presenting part as dilation advances during the first stage of labor in women who delivered vaginally without instrumentation. We propose that the mathematical expressions describing this relationship may be valuable in the assessment of first-stage labor progression.

Relative contribution of biological variation and technical variables to zone diameter variations of disc diffusion susceptibility testing.

Disc diffusion is still largely based on manual procedures. Technical variations originate from inoculum preparation, variations in materials, individual operator plate streaking and reading accuracy. Resulting measurement imprecision contributes to categorization errors. Biological variation resembles the natural fluctuation of a measured parameter such as antibiotic susceptibility around a mean value. It is deemed to originate from factors such as genetic background or metabolic state. This study analysed the relative contribution of different technical and biological factors to total disc diffusion variation. For calculation of relative error factor contribution to disc diffusion variability, five experiments were designed keeping different combinations of error factors constant. A mathematical model was developed to analyse the individual error factor contribution to disc diffusion variation for each of the tested drug-species combinations. The contribution of biological variation to total diameter variance ranged from 10.4% to 98.8% for different drug-species combinations. Highest biological variation was found for Enterococcus faecalis WT and vancomycin (98.8%) and for penicillinase-producing Staphylococcus aureus and penicillin G (96.0%). Average imprecision of automated zone reading revealed that 1.4%-5.3% of total imprecision was due to technical variation, while materials, i.e. antibiotic discs and agar plates, contributed between 2.6% and 3.9%. Inoculum preparation and manual plate streaking contributed 6.8%-24.8% and 6.6%-24.3%, respectively, to total imprecision. This study illustrates the relative contributions of technical factors that account for a significant part of total variance in disc diffusion. The highest relative contribution originated from the operator, i.e. manual inoculum preparation and plate streaking. Further standardization of inoculum preparation and plate streaking by automation could potentially increase the precision of disc diffusion and improve the correlation of susceptibility reports with clinical outcome.

Intra- and inter-examination repeatability of magnetic resonance spectroscopy, magnitude-based MRI, and complex-based MRI for estimation of hepatic proton density fat fraction in overweight and obese children and adults.

Determine intra- and inter-examination repeatability of magnitude-based magnetic resonance imaging (MRI-M), complex-based magnetic resonance imaging (MRI-C), and magnetic resonance spectroscopy (MRS) at 3T for estimating hepatic proton density fat fraction (PDFF), and using MRS as a reference, confirm MRI-M and MRI-C accuracy. Twenty-nine overweight and obese pediatric (n = 20) and adult (n = 9) subjects (23 male, 6 female) underwent three same-day 3T MR examinations. In each examination MRI-M, MRI-C, and single-voxel MRS were acquired three times. For each MRI acquisition, hepatic PDFF was estimated at the MRS voxel location. Intra- and inter-examination repeatability were assessed by computing standard deviations (SDs) and intra-class correlation coefficients (ICCs). Aggregate SD was computed for each method as the square root of the average of first repeat variances. MRI-M and MRI-C PDFF estimation accuracy was assessed using linear regression with MRS as a reference. For MRI-M, MRI-C, and MRS acquisitions, respectively, mean intra-examination SDs were 0.25%, 0.42%, and 0.49%; mean intra-examination ICCs were 0.999, 0.997, and 0.995; mean inter-examination SDs were 0.42%, 0.45%, and 0.46%; and inter-examination ICCs were 0.995, 0.992, and 0.990. Aggregate SD for each method was <0.9%. Using MRS as a reference, regression slope, intercept, average bias, and R (2), respectively, for MRI-M were 0.99%, 1.73%, 1.61%, and 0.986, and for MRI-C were 0.96%, 0.43%, 0.40%, and 0.991. MRI-M, MRI-C, and MRS showed high intra- and inter-examination hepatic PDFF estimation repeatability in overweight and obese subjects. Longitudinal hepatic PDFF change >1.8% (twice the maximum aggregate SD) may represent real change rather than measurement imprecision. Further research is needed to assess whether examinations performed on different days or with different MR technologists affect repeatability of MRS voxel placement and MRS-based PDFF measurements.

ESTIMATION OF GEOGRAPHICAL DATABASES CAPTURE SCALE BASED ON INTER-VERTICES DISTANCES EXPLORATION

Abstract. This article presents a method to estimate the capture scale of a geographical database based on the characterization of its level of detail. This contribution fits in a larger research, dealing with the development of a general model to estimate the imprecision of length and area measurements computed from the geometry of objects of weakly informed geographical databases. In order to parameterize automatically a digitizing error simulation model, the characteristic capture scale is required. Thus, after a definition of the different notions of scales in geographical databases, the proposed method is presented. The goal of the method is to model the relation between the level of detail of a geographical database, by exploring inter-vertices distances, and its characteristic capture scale. To calibrate the model, a digitizing test experiment is provided, showing a clear relation between median intervertices distance and characteristic capture scale. The proposed knowledge extraction method proves to be the usefull in order to parameterize the measurement imprecision estimation model, and more generally to inform the database user when the capture scale is unknown. Nevertheless, further experiments need to be provided to improve the method, and model the relation between level of detail and capture scale with more efficiency.

Critical appraisal of the role of ruxolitinib in myeloproliferative neoplasm-associated myelofibrosis.

The recent approval of molecular-targeted therapies for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF) has dramatically changed its therapeutic landscape. Ruxolitinib, a JAK1/JAK2 tyrosine kinase inhibitor, is now widely used for first- and second-line therapy in persons with MPN-MF, especially those with disease-related splenomegaly, intermediate- or high-risk disease, and constitutional symptoms. The goal of this work is to critically analyze data supporting use of ruxolitinib in the clinical settings approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). We systematically reviewed the literature and analyzed the risk of biases in the two randomized studies (COMFORT I and COMFORT II) on which FDA and EMA approval was based. Our strategy was to apply the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach by evaluating five dimensions of evidence: (1) overall risk of bias, (2) imprecision, (3) inconsistency, (4) indirectness, and (5) publication bias. Based on these criteria, we downgraded the evidence from the COMFORT I and COMFORT II trials for performance, attrition, and publication bias. In the disease-associated splenomegaly sphere, we upgraded the quality of evidence because of large effect size but downgraded it because of comparator choice and outcome indirectness (quality of evidence, low). In the sphere of treating persons with intermediate- or high-risk disease, we downgraded the evidence because of imprecision in effect size measurement and population indirectness. In the sphere of disease-associated symptoms, we upgraded the evidence because of the large effect size, but downgraded it because of comparator indirectness (quality of evidence, moderate). In conclusion, using the GRADE technique, we identified factors affecting the quality of evidence that were otherwise unstated. Identifying and evaluating these factors should influence the confidence with which physicians use ruxolitinib in persons with MPN-MF.

Review of Thirteen Years of CTS Winery Laboratory Collaborative Data

Data from 13 years (78 wines) of wine industry laboratory proficiency testing were reviewed. After outlier removal, within-laboratory precision (repeatability) and across-laboratory precision (reproducibility) were determined for measurements of alcohol, titratable acidity, volatile acidity, total SO₂, free SO₂, malic acid, specific gravity, pH, residual sugar, glucose plus fructose, and absorbance at 420 and 520 nm. Reproducibility was 3.6 to 57.8 times higher than repeatability. Reproducibility was evaluated with Horwitz ratios (HorRat); only alcohol, titratable acid, and total SO₂ had acceptable values (mean HorRat &lt;2). Measurement z scores demonstrated non-normal distributions, particularly for specific gravity, likely due to confounding with density. Reproducibility did not vary significantly over time, with exceptions: imprecision of ethanol measurements decreased (improved) by 0.0084% v/v per year, while the imprecision of titratable acidity, pH, and malic acid measurements increased by 0.0089 g/L as tartaric, 0.0008 pH units, and 0.13 g malic acid/L per year, respectively. The imprecision of reproducibility and repeatability generally increased with analyte concentration, with notable exceptions for alcohol (both), volatile acidity (reproducibility), and total SO₂ (repeatability). The methods or instruments used to determine alcohol, titratable acidity, free and total SO₂, and volatile acidity changed significantly over time. Significant differences were observed among techniques for many analytes, which can be rationalized by attribution to well-known matrix effects manageable in a properly run method; e.g., higher apparent concentrations of alcohol by boiling point methods in high-sugar matrices. Evaluation of method accuracy was not possible due to the lack of wine reference materials with known true values. Results demonstrate the need for industry-wide improvement in analytical performance for some assays, and the potential benefit of adopting criteria guidelines for method performance.

Does neighbourhood deprivation cause poor health? Within-individual analysis of movers in a prospective cohort study

Neighbourhood deprivation has been associated with poor health. The evidence for social causation, however, remains scarce because selective residential mobility may also create neighbourhood differences. The present study examined whether individuals had poorer health when they were living in a deprived neighbourhood compared to another time when the same individuals were living in a less deprived neighbourhood. Participants were from the British Household Panel Survey prospective cohort study with 18 annual measurements of residential location and self-reported health outcomes between 1991 and 2009 (n=137 884 person-observations of 17 001 persons in England). Neighbourhood deprivation was assessed concurrently with health outcomes using the Index of Multiple Deprivation at the geographically detailed level of Lower Layer Super Output Areas. The main analyses were replicated in subsamples from Scotland (n=4897) and Wales (n=4442). Multilevel regression was used to separate within-individual and between-individuals associations. Neighbourhood deprivation was associated with poorer self-rated health, and with higher psychological distress, functional health limitations and number of health problems. These associations were almost exclusively due to differences between different individuals rather than within-individual variations related to different neighbourhoods. By contrast, poorer health was associated with lower odds of moving to less deprived neighbourhoods among movers. The analysis was limited by the restricted within-individual variation and measurement imprecision of neighbourhood deprivation. Individuals living in deprived neighbourhoods have poorer health, but it appears that neighbourhood deprivation is not causing poorer health of adults. Instead, neighbourhood health differentials may reflect the more fundamental social inequalities that determine health and ability to move between deprived and non-deprived neighbourhoods.

Functional and Structural Methods With Mixed Measurement Error and Misclassification in Covariates

Covariate measurement imprecision or errors arise frequently in many areas. It is well known that ignoring such errors can substantially degrade the quality of inference or even yield erroneous results. Although in practice both covariates subject to measurement error and covariates subject to misclassification can occur, research attention in the literature has mainly focused on addressing either one of these problems separately. To fill this gap, we develop estimation and inference methods that accommodate both characteristics simultaneously. Specifically, we consider measurement error and misclassification in generalized linear models under the scenario that an external validation study is available, and systematically develop a number of effective functional and structural methods. Our methods can be applied to different situations to meet various objectives.

On Designing Resilient Location-Privacy Obfuscators

The success of location-based services is growing together with the diffusion of GPS-equipped smart devices. As a consequence, privacy concerns are raising year by year. Location privacy is becoming a major interest in research and industry world, and many solutions have been proposed for it. One of the simplest and most flexible approaches is obfuscation, in which the precision of location data is artificially degraded before disclosing it. In this paper, we present an obfuscation approach capable of dealing with measurement imprecision, multiple levels of privacy, untrusted servers and adversarial knowledge of the map. We estimate its resistance against statistical-based deobfuscation attacks, and we improve it by means of three techniques, namely extreme vectors, enlarge-and-scale and hybrid vectors.

The impact of measurement frequency on the domains of glycemic control in the critically ill--a Monte Carlo simulation.

The role of blood glucose (BG) measurement frequency on the domains of glycemic control is not well defined. This Monte Carlo mathematical simulation of glycemic control in a cohort of critically ill patients modeled sets of 100 patients with simulated BG-measuring devices having 5 levels of measurement imprecision, using 2 published insulin infusion protocols, for 200 hours, with 3 different BG-measurement intervals-15 minutes (Q15'), 1 hour (Q1h), and 2 hours (Q2h)-resulting in 1,100,000 BG measurements for 3000 simulated patients. The model varied insulin sensitivity, initial BG value and rate of gluconeogenesis. The primary outcomes included rates of hyperglycemia (BG > 180 mg/dL), hypoglycemia (BG < 70 and 40 mg/dL), proportion of patients with elevated glucose variability (within-patient coefficient of variation [CV] > 20%), and time in range (BG ranges 80-150 mg/dL and 80-180 mg/dL). Percentages of hyperglycemia, hypoglycemia at both thresholds, and patients with elevated glucose variability as well as time outside glycemic targets were substantially higher in simulations with measurement interval Q2h compared to those with measurement interval Q1h and moderately higher in simulations with Q1h than in those with Q15'. Higher measurement frequency mitigated the deleterious effect of high measurement imprecision, defined as CV ≥ 15%. This Monte Carlo simulation suggests that glycemic control in critically ill patients is more optimal with a BG measurement interval no longer than 1h, with further benefit obtained with use of measurement interval of 15'. These findings have important implications for the development of glycemic control standards.

Flux and Position Observer of Permanent Magnet Synchronous Motors with Relaxed Persistency of Excitation Conditions

In this paper we propose a flux and position observer for permanent magnet synchronous motors when voltages, currents and rotor speed are available for measurement. We prove that this observer converges under weaker assumptions than the classical persistence of excitation condition. Simulations confirm the eficacy of the proposed observer and show that it can cope with imprecision in rotor speed measurement, which allows to use an estimator when the speed cannot be measured directly.

ADVANCING RESEARCH BY CLEARLY LABELING MEASURES OF PHYSICAL FUNCTION: EXTRACTING AMBULATION AND STAIR-CLIMBING FROM “MOBILITY DISABILITY”

The term “mobility disability” is used in different academic disciplines to discuss conceptualizations of physical movement. Inadequate attention has been paid to how this umbrella term refers to various forms of measurements on both hypothetical and enacted function. Refining what is meant by mobility disability may impact clinical practice by providing more specific information to clinicians. Less ambiguous labeling may have the potential to advance research by lowering measurement imprecision. We complement discussion by presenting empirical analysis on 5,995 participants (aged &gt; 65) from National Health and Aging Trends Study (NHATS-2011). Ambiguous labeling of mobility may unintentionally obscure what is known about perceived capacity for ambulation and stair-climbing. Because creating low-cost and readily-available measures of health in the population has the potential to advance public health knowledge, efforts should continue to standardize and clarify measures of mobility.

Utility of ketone measurement in the prevention, diagnosis and management of diabetic ketoacidosis.

Ketone measurement is advocated for the diagnosis of diabetic ketoacidosis and assessment of its severity. Assessing the evidence base for ketone measurement in clinical practice is challenging because multiple methods are available but there is a lack of consensus about which is preferable. Evaluating the utility of ketone measurement is additionally problematic because of variability in the biochemical definition of ketoacidosis internationally and in the proposed thresholds for ketone measures. This has led to conflicting guidance from expert bodies on how ketone measurement should be used in the management of ketoacidosis. The development of point-of-care devices that can reliably measure the capillary blood ketone β-hydroxybutyrate (BOHB) has widened the spectrum of applications of ketone measurement, but whether the evidence base supporting these applications is robust enough to warrant their incorporation into routine clinical practice remains unclear. The imprecision of capillary blood ketone measures at higher values, the lack of availability of routine laboratory-based assays for BOHB and the continued cost-effectiveness of urine ketone assessment prompt further discussion on the role of capillary blood ketone assessment in ketoacidosis. In the present article, we review the various existing methods of ketone measurement, the precision of capillary blood ketone as compared with other measures, its diagnostic accuracy in predicting ketoacidosis and other clinical applications including prevention, assessment of severity and resolution of ketoacidosis.

Estimation of birthweight by measurement of fetal thigh soft-tissue thickness improves the detection of macrosomic fetuses.

The accuracy of sonographic estimation of birthweight in suspected macrosomic fetuses is compromised by the imprecision of the biometrical measurements. This prospective study evaluated the performance of an equation based on linear measurement of the soft tissue above the external side of the fetal femur. The performance of this algorithm was compared with two classical algorithms. Sonographic measurements were taken within 48 h before of delivery. Sixty-two patients with fetuses with suspected macrosomia were enrolled. The studied formulas were compared between them and showed a significant correlation with birthweight (p < 0.0001) and satisfactory statistical performances (r > 0.9). The new formula showed a reduced standard deviation that means a lower internal error in the prediction. This study supports the potential of this new approach for the estimation of birthweight in large fetuses based on sonographic linear measurements only.

Selecting proper uncertainty model for steady-state data reconciliation – Application to mineral and metal processing industries

Data reconciliation is widely applied in mineral and metal processing plants to improve information quality. Imprecision, unreliability and incompleteness of measurements are common problems motivating the implementation of the technique. Current practices rely on mass and energy conservation constraints to estimate the underlying steady-state values of process variables. Typically, the Gaussian context is assumed and a Maximum-Likelihood estimator is selected. The performance of such an estimator depends on the covariance matrices used to characterize model and measurement uncertainties. In practice, determining these covariance matrices is a challenging task that is often overlooked. Using inappropriate uncertainty models, based on simplistic or improper hypotheses, can lead to unexpected underperformances. The objective of the paper is to illustrate the impact of correctly selecting uncertainty covariance matrices for steady-state data reconciliation. Different case-studies involving a combustion chamber, a hydrocyclone, a flotation circuit, and a separation unit are used for investigating the sensitivity of the algorithm to the structure of covariance matrices. An example based on Monte-Carlo simulations is presented to assess the importance of assigning right values to variance terms. Simulation results show that the adjustment of uncertainty covariance matrices has a significant influence on the precision of estimates and reveal that some common tuning practices can have detrimental effects.

The function of neurocognitive networks: Comment on “Understanding brain networks and brain organization” by Pessoa

Pessoa [5] has performed a valuable service by reviewing the extant literature on brain networks and making a number of interesting proposals about their cognitive function. The term function is at the core of understanding the brain networks of cognition, or neurocognitive networks (NCNs) [1]. The great Russian neuropsychologist, Luria [4], defined brain function as the common task executed by a distributed brain network of complex dynamic structures united by the demands of cognition. Casting Luria in a modern light, we can say that function emerges from the interactions of brain regions in NCNs as they dynamically self-organize according to cognitive demands. Pessoa rightly details the mapping between brain function and structure, emphasizing both its pluripotency (one structure having multiple functions) and degeneracy (many structures having the same function). However, he fails to consider the potential importance of a one-to-one mapping between NCNs and function. If NCNs are uniquely composed of specific collections of brain areas, then each NCN has a unique function determined by that composition. Luria’s definition implies that NCNs are highly versatile: by dynamically uniting brain areas in a large number of different combinations as demanded by a broad range of cognitive demands, they perform a wide variety of functions. However, the attribution of function to an NCN may not always be straightforward given the limited repertoire of available behavioral paradigms, the lack of knowledge of the cognitive demands required, and the imprecision of NCN measurement. As an example of this difficulty, the function “face recognition” may be attributed to a distributed set of ventral occipital and temporal regions that are active when subjects recognize faces, but “face recognition” may not adequately describe all the functions of the various NCNs that involve these areas. The composition, and hence the function, of NCNs may be idiosyncratic, changing with the cognitive demands imposed by a particular behavior performed by a given individual. Finally, for Pessoa, functional connectivity is largely undirected and measured by correlation. This emphasis ignores the directedness of structural connectivity in the brain: the axons of neurons in the brain leave the soma, travel