The COVID-19 pandemic has put unprecedented pressure on public health resources around the world. From adversity, opportunities have arisen to measure the state and dynamics of human disease at a ...scale not seen before. In the United Kingdom, the evidence that wastewater could be used to monitor the SARS-CoV-2 virus prompted the development of National wastewater surveillance programmes. The scale and pace of this work has proven to be unique in monitoring of virus dynamics at a national level, demonstrating the importance of wastewater-based epidemiology (WBE) for public health protection. Beyond COVID-19, it can provide additional value for monitoring and informing on a range of biological and chemical markers of human health. A discussion of measurement uncertainty associated with surveillance of wastewater, focusing on lessons-learned from the UK programmes monitoring COVID-19 is presented, showing that sources of uncertainty impacting measurement quality and interpretation of data for public health decision-making, are varied and complex. While some factors remain poorly understood, we present approaches taken by the UK programmes to manage and mitigate the more tractable sources of uncertainty. This work provides a platform to integrate uncertainty management into WBE activities as part of global One Health initiatives beyond the pandemic.
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•Wastewater is a relatively unbiased medium transporting multiple markers of human health.•Biological- and chemical-based Wastewater-Based Epidemiology provides flexibility and resilience for public health security.•Measurements of target analytes in wastewater are subject to variability and uncertainty.•Identifying and mitigating uncertainty requires multi-disciplinary collaboration.•UK wastewater monitoring programmes have generated a substantial data resource to derive better understanding of uncertainty.
Background
On‐site deferral for low hemoglobin (Hb) is common in most countries and deferral rates commonly vary between 1% and 20%. Blood banks continuously strive to reduce deferral rates as these ...imply an immediate loss of products, a waste of materials, a waste of staff and donor time, and potential loss of donors. Despite many efforts, the main cause of donor deferral—the variability in hemoglobin measurement outcomes—remains largely unaddressed.
Study Design and Methods
Repeated hemoglobin measurements obtained at donor intake were used to estimate the variability in measurement outcomes (measurement variability). This information is incorporated in a new algorithm for donor deferral where the mean hemoglobin level of a donor is used to determine both donor eligibility and the deviance of individual measurement outcomes. The algorithm was tested on a cohort of new Dutch donors that started between 2012 and 2022 to evaluate its impact on the donor deferral rate.
Results
Historical data from 439,376 new donors with a deferral rate of 5.3% were analyzed by applying the new donor deferral algorithm. It was found that 92% of all deferrals were unnecessary as Hb levels were within the range of expected measurement variability. Contrarily, it appeared that 460 donors (0.10%) made 704 donations (0.06%) whilst not complying with donor eligibility criteria.
Discussion
Not accounting for measurement variability can be shown to not only result in unnecessary on‐site deferrals but also results in donations by donors that can be shown not to comply with the legally required minimum Hb levels.
Background
Margin distance contributes to survival and recurrence during wedge resections for early‐stage non‐small cell lung cancer. The Initiative for Early Lung Cancer Research on Treatment sought ...to standardize a surgeon‐measured margin intraoperatively.
Methods
Lung cancer patients who underwent wedge resection were reviewed. Margins were measured by the surgeon twice as per a standardized protocol. Intraobserver variability as well as surgeon–pathologist variability were compared.
Results
Forty‐five patients underwent wedge resection. Same‐surgeon measurement analysis indicated good reliability with a small mean difference and narrow limit of agreement for the two measures. The median surgeon‐measured margin was 18.0 mm, median pathologist‐measured margin was 16.0 mm and the median difference between the surgeon–pathologist margin was −1.0 mm, ranging from −18.0 to 12.0 mm. Bland–Altman analysis for margin measurements demonstrated a mean difference of 0.65 mm. The limit of agreement for the two approaches were wide, with the difference lying between −16.25 and 14.96 mm.
Conclusions
A novel protocol of surgeon‐measured margin was evaluated and compared with pathologist‐measured margin. High intraobserver agreement for repeat surgeon measurements yet low‐to‐moderate correlation or directionality between surgeon and pathologic measurements were found.
Discussion
A standardized protocol may reduce variability in pathologic assessment. These findings have critical implications considering the impact of margin distance on outcomes.
The upcoming Fluorescence Explorer (FLEX) satellite mission aims to provide high quality radiometric measurements for subsequent retrieval of sun-induced chlorophyll fluorescence (SIF). The ...combination of SIF with other observations stemming from the FLEX/Sentinel-3 tandem mission holds the potential to assess complex ecosystem processes. The calibration and validation (cal/val) of these radiometric measurements and derived products are central but challenging components of the mission. This contribution outlines strategies for the assessment of in situ radiometric measurements and retrieved SIF. We demonstrate how in situ spectrometer measurements can be analysed in terms of radiometric, spectral and spatial uncertainties. The analysis of more than 200 k spectra yields an average bias between two radiometric measurements by two individual spectrometers of 8%, with a larger variability in measurements of downwelling radiance (25%) compared to upwelling radiance (6%). Spectral shifts in the spectrometer relevant for SIF retrievals are consistently below 1 spectral pixel (up to 0.75). Found spectral shifts appear to be mostly dependent on temperature (as measured by a temperature probe in the instrument). Retrieved SIF shows a low variability of 1.8% compared with a noise reduced SIF estimate based on APAR. A combination of airborne imaging and in situ non-imaging fluorescence spectroscopy highlights the importance of a homogenous sampling surface and holds the potential to further uncover SIF retrieval issues as here shown for early evening acquisitions. Our experiments clearly indicate the need for careful site selection, measurement protocols, as well as the need for harmonized processing. This work thus contributes to guiding cal/val activities for the upcoming FLEX mission.
•Spectral, radiometric and SIF retrieval-related uncertainties are explored.•The investigated sources of uncertainty are relevant for SIF cal/val activities.•This work contributes to the design and implementation of SIF cal/val networks.•A thorough design of site infrastructure and analysis capability is important.•Spatial heterogeneity is a crucial aspect in SIF mission cal/val.
Precis: In a trio of prospective studies, the iCare rebound tonometer demonstrated significantly lower test-retest variability than Goldmann tonometry with good interoperator and interdevice ...reproducibility, supporting its value in monitoring intraocular pressure (IOP) changes over time. Purpose: The purpose of this study was to characterize intraoperator and interoperator and interdevice reliability of IOP measurements with rebound tonometry (RT, ic100). Methods: Three prospective cross-sectional studies were conducted in distinct sample of adult patients with established glaucoma, suspected glaucoma, or no glaucoma at the West Virginia University Eye Institute. Participants in study 1 underwent 5 RT measurements in one randomly selected eye and 5 Goldmann tonometry measurements in the fellow eye by 1 operator; intraoperator variability was compared using the F test. In study 2, 3 operators each obtained 3 RT measurements in participants in randomized operator order. In study 3, a single operator collected 3 measurements each with 3 RTs in randomized device order. Between-operator and between-device reproducibility were characterized using intraclass correlation coefficients (ICCs). Results: Overall, 28, 19, and 25 subjects participated in the 3 respective studies. Within-subject variance across subjects was 0.757 in RT measurements and 2.471 in Goldmann measurements ( P =0.0035). Interoperator reproducibility of RT measurements was good in both eyes ICC for right eyes 0.78, 95% confidence interval (CI): 0.60-0.85; ICC for left eyes 0.75, 95% CI: 0.50-0.83. Interdevice reproducibility of RT measurements was good approaching excellent (ICC for right eyes 0.87, 95% CI: 0.83-0.90; ICC for left eyes 0.89, 95% CI: 0.86-0.91). Conclusions: The RT’s lower measurement variability and good interoperator and interdevice reproducibility suggest that it can characterize IOP changes over time more robustly than Goldmann tonometry, aiding clinicians in assessing the effectiveness of glaucoma therapy and the consistency of IOP control.
The nociceptive flexion reflex (NFR) and its threshold are frequently used to investigate spinal nociception in humans. Since this threshold (NFRT) is a probabilistic measure, specific algorithms are ...used for NFRT estimation based on the stochastic occurrence of reflexes at different stimulus intensities. We used a validated simulation model of the NFR to investigate the amount of NFRT measurement variability induced by different estimation algorithms in a steady setting of reduced external influences.
We simulated the behavior of different estimation algorithms in subjects with an artificially steady baseline NFRT variability (standard deviation: 0 mA) or low baseline NFRT variability (standard deviation: 0.156 mA), equaling a quiet experimental setting. The obtained data were analyzed for NFRT measurement variability caused by the algorithms compared to the baseline variability reflecting other physiological influences.
The standard deviation of the NFRT estimated by the different algorithms ranged between 0.381 and 3.464 mA with 96.8% to 99.6% of the measurement variability attributed to the algorithm used. Out of the investigated algorithms the dynamic staircase algorithm was most precise.
The NFRT measurement variability observed during quiet and steady experimental sessions is mostly caused by the properties of the estimation algorithms, due to the probabilistic nature of the reflex occurrence. Our results give reference for choosing the optimal estimation algorithm to improve measurement precision.
•Presented the workflow for the application of a geochemically informed leak detection (GILD) model to an idealized carbon storage site on the Gulf Coast.•Illustrated a method for characterizing ...measurement variability from background data.•Constructed and fitted Bayesian belief network (BBN) models to predict the probability of CO2 leak detection as a function of the size of the leak and the magnitude of measurement variability.•Quantified the effect of measurement variability on leak detection capabilities of monitoring parameters.
The Gulf Coast region possesses great potential for CO2 enhanced oil recovery (EOR) and CO2 storage. A geochemically informed leak detection (GILD) model has been applied to CO2 injection sites on the Gulf Coast with considerations of measurement variability. The Jasper aquifer in Montgomery County, Texas, was chosen to demonstrate the method. Based on background data from wells in the area, combinations of mineral and fluid compositions were used to create 23 scenarios for the geochemical model. The output from the geochemical model was used to identify sensitive monitoring species, and response functions were generated for these as a function of the CO2 leakage concentration. The sources of measurement variability for background conditions were characterized from the Jasper aquifer background data, and then normalized using the coefficient of variation of each species across the monitoring wells. Bayesian belief network (BBN) models were constructed, and measurement variability of different levels were added to compare leak detection probabilities. Increasing measurement variability decreased the power to detect a leak of a given size. For a moderately high CO2 concentration of 0.2 mol/kg, the probability of detecting this leakage effect using pH as the monitoring variable in an aquifer with calcite decreases from 98% (no measurement variability) to 61% (medium variability) to 33% (high variability). The loss in power of the sampling protocol with increasing measurement variability is similar in magnitude when Ca2+ or HCO3− is used as the monitoring parameter, but only for aquifers with calcite.
OBJECTIVESThe aims of this study were to analyze the effect of dual-energy computed tomography (DECT) scanners and fluid characteristics on iodine quantification and to calculate the measurement ...variability range induced by those variables.
METHODSWe performed an experimental phantom study with 4 mediastinal iodine phantoms. Each phantom contained 6 tubes of different iodine concentrations (0, 1.0, 2.5, 5.0, 10.0, and 20.0 mg/mL) diluted in a specific solvent, which was water, 10% amino acid solution, 20% lipid emulsion, or 18% calcium solution, respectively. Mediastinal phantoms were inserted into an anthropomorphic chest phantom and were scanned with 3 different DECT scanners from 3 vendors using 2 radiation dosage settings. Iodine density (IoD) and computed tomography (CT) attenuation at virtual monoenergetic 70-keV images and virtual nonenhanced images were measured for the iodine phantoms. The effects of DECT scanners, solvents, and radiation dosage on the absolute measurement error of IoD and on the CT attenuation profiles were investigated using linear mixed-effects models. Measurement variability range of IoD was also determined.
RESULTSAbsolute error of IoD was not significantly affected by the DECT systems, kind of solvents, and radiation dosage settings. However, CT attenuation profiles were significantly different among the DECT vendors and simulated body fluids. Measurement variability range of IoD was from −0.6 to 0.4 mg/mL for the true iodine concentration 0 mg/mL.
CONCLUSIONSDual-energy CT systems and fluid characteristics did not have a significant effect on the IoD measurement accuracy. A cutoff of IoD for the determination of a truly enhancing lesion on DECT would be 0.4 mg/mL.
The goal of the present research study was to investigate possible differences in nasalance scores between different Nasometer headgears. Frequency response characteristics of microphone pairs in a ...Nasometer model 6200, a model 6450 and two model 6500 headsets were compared using long-term average spectra of white noise and multi-speaker babble signals. Prerecorded sound files from a male and a female speaker were used to record nasalance scores with the four Nasometer headsets and to calculate cumulative absolute differences within and between the headsets. The main outcome measures were the cumulative absolute differences between the decibel (dB) values in the frequency bins from 300 to 750 Hz for the nasal and oral channels of each microphone pair. Cumulative absolute differences between nasalance scores of repeated stimuli within and across Nasometer headsets were tabulated. Results showed that cumulative absolute differences for the frequency range 300-750 Hz were between 6.58 and 7.68 dB. Within headsets, 95.6% to 100% of measurements of all four Nasometer headsets were within 3 nasalance points, although test-retest differences of up to 6 nasalance points were found. Between headsets, 56.1% to 98.9% of measurements were within 3 nasalance points, with the single largest difference of 8 nasalance points. In conclusion, differences between repeated nasalance scores obtained with the same and different headsets were noted. Clinicians should allow a margin of error of ±6 to 8 nasalance points when interpreting scores from different Nasometer headsets.
OBJECTIVES: Carotid Doppler ultrasound is used as a measure of fluid responsiveness, however, assessing change with statistical confidence requires an adequate beat sample size. The coefficient of ...variation helps quantify the number of cardiac cycles needed to adequately detect change during functional hemodynamic monitoring. DESIGN: Prospective, observational, human model of hemorrhage and resuscitation. SETTING: Human physiology laboratory at Mayo Clinic. SUBJECTS: Healthy volunteers. INTERVENTIONS: Lower body negative pressure. MEASUREMENTS AND MAIN RESULTS: We measured the coefficient of variation of the carotid artery velocity time integral and corrected flow time during significant cardiac preload changes. Seventeen-thousand eight-hundred twenty-two cardiac cycles were analyzed. The median coefficient of variation of the carotid velocity time integral was 8.7% at baseline and 11.9% during lowest-tolerated lower body negative pressure stage. These values were 3.6% and 4.6%, respectively, for the corrected flow time. CONCLUSIONS: The median coefficient of variation values measured in this large dataset indicates that at least 6 cardiac cycles should be averaged before and after an intervention when using the carotid artery as a functional hemodynamic measure.
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