Lower Relative Variability Research Articles

Improving the Reliability of Peer Review Without a Gold Standard

Peer review plays a crucial role in accreditation and credentialing processes as it can identify outliers and foster a peer learning approach, facilitating error analysis and knowledge sharing. However, traditional peer review methods may fall short in effectively addressing the interpretive variability among reviewing and primary reading radiologists, hindering scalability and effectiveness. Reducing this variability is key to enhancing the reliability of results and instilling confidence in the review process. In this paper, we propose a novel statistical approach called “Bayesian Inter-Reviewer Agreement Rate” (BIRAR) that integrates radiologist variability. By doing so, BIRAR aims to enhance the accuracy and consistency of peer review assessments, providing physicians involved in quality improvement and peer learning programs with valuable and reliable insights. A computer simulation was designed to assign predefined interpretive error rates to hypothetical interpreting and peer-reviewing radiologists. The Monte Carlo simulation then sampled (100 samples per experiment) the data that would be generated by peer reviews. The performances of BIRAR and four other peer review methods for measuring interpretive error rates were then evaluated, including a method that uses a gold standard diagnosis. Application of the BIRAR method resulted in 93% and 79% higher relative accuracy and 43% and 66% lower relative variability, compared to “Single/Standard” and “Majority Panel” peer review methods, respectively. Accuracy was defined by the median difference of Monte Carlo simulations between measured and pre-defined “actual” interpretive error rates. Variability was defined by the 95% CI around the median difference of Monte Carlo simulations between measured and pre-defined “actual” interpretive error rates. BIRAR is a practical and scalable peer review method that produces more accurate and less variable assessments of interpretive quality by accounting for variability within the group’s radiologists, implicitly applying a standard derived from the level of consensus within the group across various types of interpretive findings.

Using continuous electrical conductivity measurements to derive major solute concentrations in karst systems

AbstractHydrochemical data of karst springs provide valuable insights into the internal hydrodynamical functioning of karst systems and support model structure identification. However, the collection of high‐frequency time series of major solute species is limited by analysis costs. In this study, we develop a method to retrieve the individual solute concentration time series and their uncertainty at high temporal resolution for karst springs by using continuous observations of electrical conductivity () and low‐frequency ionic measurements. Due to the large ion content and non‐negligible concentrations of aqueous complexes in karst systems, the concentration of each solute species occurring as free ion and as part of aqueous complexes are computed separately. The concentration of species occurring as free ions are computed considering their contributions to the total , whereas the concentration of the species as part of complexes are obtained from speciation calculations. The pivotal role of the complexation processes for the reconstruction of solute concentration time series starting from the signal is investigated in two karstic catchments with different geologies and temporal resolution of the available hydrochemical datasets, that is the Kerschbaum dolostone system in Austria and the Baget limestone system in France. The results show that complexation processes are significant and should be considered for the estimation of the total solute concentration in case of SO4, Ca, Mg and HCO3. The signal of a karst spring can be used to interpolate and quantify the dynamics of those solutes characterized by large contribution (approximately >6%) to the total and low relative variability, that is HCO3, Ca and Mg. Moreover, the presented method can be used to estimate concentrations of solutes when applied to karst systems with stationary and hydrogeochemical homogeneous contributing area. On the contrary, the method is affected by large uncertainty in case of dynamic systems characterized by varying contributions of water from different geological areas. This study aims to contribute to the problem of hydrogeochemical data availability and to support future works on karst systems conceptualization.

Large-Scale Assessment of Scan-Time Variability and Multiple-Procedure Efficiency for Cross-Sectional Neuroradiological Exams in Clinical Practice.

Scheduling of CT and MR exams requires reasonable estimates for expected scan duration. However, scan-time variability and efficiency gains from combining multiple exams are not quantitatively well characterized. In this work, we developed an informatics approach to quantify typical duration, duration variability, and multiple-procedure efficiency on a large scale, and used the approach to analyze 48,766 CT- and MR-based neuroradiological exams performed over one year. We found MR exam durations demonstrated higher absolute variability, but lower relative variability and lower multiple-procedure efficiency, compared to CT exams (p < 0.001). Our approach enables quantification of real-world operational performance and variability to inform optimal patient scheduling, efficient resource utilization, and sustainable service planning.

Abstract 580: A method for estimating mutation load from tumor research samples using a targeted next-generation sequencing panel

Abstract Introduction: Tumor mutation load predicts durable benefit from immune checkpoint inhibitors in several cancer types. Existing methods to estimate tumor mutation load have large input DNA and extensive infrastructure requirements and are associated with delays due to shipping precious biopsy samples to central laboratories. Herein, we demonstrate the ability of a targeted panel with fast turn-around time to estimate mutation load from tumor research samples using low input. Methods: We developed a single sample analysis workflow to estimate mutation load (mutation count per megabase) from FFPE and fresh frozen tumor research samples. The assay utilizes a PCR-based target enrichment panel that covers 409 genes and 1.7 Mb of genomic regions. The workflow requires only 10 ng of input DNA, and enables a 2.5-day turn-around time from sample to the final report. The workflow enables &amp;lt; 60 minutes of hands-on time for automated library preparation and templating on a batch of 8 samples. Sequencing is performed on high throughput semiconductor sequencing platform to achieve sufficient depth (~500x coverage) and accuracy. Our analysis pipeline calls variants at ≥5% allelic frequency with parameters optimized for high accuracy. The workflow is tumor sample only, with no matched normal sample required, and germ-line variants, along with background noise, are removed through application of filters based on variants prevalent in population databases. Results: In-silico analysis demonstrated that the predicted mutation counts associated with the covered regions of the targeted panel could effectively stratify responders and non-responders to immune checkpoint inhibitors in 3 separate cohorts with high statistical significance. The assay was applied to colorectal specimens previously typed for microsatellite instability (MSI) and distinguished samples that were MSI-H (median mutation count 94.5) and MSS (median mutation count 17.8). Matched tumor-normal analyses on 7 colorectal tumor samples showed that the single tumor analysis workflow detected somatic mutations with strong correlation (r = 0.97) with tumor-normal analysis. To assess reproducibility, we compared somatic mutation count in 6 library replicates of breast cancer cell line HCC1143 and observed low relative variability (CV=9.57%) with 19.17 average mutation count. The analysis report characterizes substitution type and context of somatic mutations, and highlights mutation signatures consistent with UV damage and spontaneous deamination of 5-methyl-cytosine, as well as FFPE deamination. Conclusions: We developed a simple analysis workflow on the Ion Torrent sequencing platform with an AmpliSeq panel to estimate mutation load from FFPE and fresh frozen tumor research samples. This solution will advance research in immuno-oncology. Citation Format: Ruchi Chaudhary, Dinesh Cyanam, Vinay Mittal, Warren Tom, Janice Au-Young, Seth Sadis, Fiona Hyland. A method for estimating mutation load from tumor research samples using a targeted next-generation sequencing panel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 580.

Task-Oriented Control of Muscle Coordination during Cycling

This study investigated the effects of different biomechanical constraints on the variability of muscle activation during cycling. Fifteen male athletes cycled at a power of 150 and 300 W. Surface EMG was recorded from seven lower limb muscles. Wavelet transformed EMG signals of all muscles were subjected to a principal component analysis to study the variability of the EMG. The full vector space was reduced to the first principal components that explained 90% of the variance. The input data of each cycle revolution were projected onto these principal component vectors. Means and SD of the projections were calculated across all cycles and summed across all time points. The relative variability (RV) was expressed as the ratio between the SD and the mean of the summed projections. The principal angle was calculated between the principal components used for the 150-W condition and those used for the 300-W condition. The RV could be split into low- and high-variability components. The variability was smaller for the lower ordered eigenvectors compared with the higher ordered ones (P < 0.001) independent of the loading condition. Overall, the 300-W condition showed lower RV compared with the 150-W condition (P < 0.01). The average principal angle between the 150- and 300-W subspaces was 0.4, respectively. Structured aspects of variability were found in the muscle activation of lower leg muscles during cycling. In the context of the minimum intervention principal, this might be interpreted as a transition into a regime that requires specific necessary muscles where the increased constraints of the task specify the muscle coordination pattern in a more precise way.

High usual dietary vitamin K intake is associated with low relative variability in vitamin K intake: implications for anticoagulant therapy

High usual dietary vitamin K intake is associated with low relative variability in vitamin K intake: implications for anticoagulant therapy

Road‐Based Surveys for Estimating Wild Turkey Density in the Texas Rolling Plains

Abstract: Line‐transect‐based distance sampling has been used to estimate density of several wild bird species including wild turkeys (Meleagris gallopavo). We used inflatable turkey decoys during autumn (Aug‐Nov) and winter (Dec‐Mar) 2003‐2005 at study sites in the Texas Rolling Plains, USA, to simulate Rio Grande wild turkey (M. g. intermedia) flocks. We evaluated detectability of flocks using logistic regression models. Our modeling effort suggested that distance to a flock and flock size played important roles in flock detectability. We also conducted surveys from roads for wild turkeys during November 2004‐January 2006. The detection probability of decoy flocks was similar to wild turkey flocks during winter (decoy flock, 69.3 ± 6.2% [x̄ ± 95% CI]; wild turkey flock, 62.2 ± 18.3%) and autumn (decoy flock, 44.1 ± 5.1%; wild turkey flock, 44.7 ± 25.6%), which suggested that using decoys was appropriate for evaluating detectability of wild turkey flocks from roads. We conducted computer simulations to evaluate the performance of line‐transect‐based distance sampling and examined the power to detect trends in population change. Simulations suggested that population density may be underestimated by 12% during inter and 29% during autumn. Such bias occurred because of incomplete detectability of flocks near roads. Winter surveys tended to have less bias, lower relative variability, and greater power than did autumn surveys. During winter surveys, power was sufficient (≥0.80) to detect a 10‐25% change in population density in 8‐12 years using ≥100 16‐km transects or ≥80 32‐km transects. We concluded line‐transect‐based distance sampling from roads is an efficient, effective, and inexpensive technique for monitoring Rio Grande wild turkey populations across large scales.

Degree of Throat Deposition Can Explain the Variability in Lung Deposition of Inhaled Drugs

Inhalation is a mainstay for treatment of asthma, and lung deposition can be seen as a surrogate marker for the ensuing clinical effects. Not only absolute lung deposition, but also its variability is of interest, as it indicates the range of expected lung deposition in an individual patient when prescribing the drug and the expected day-to-day variability when using it. A literature survey found 71 studies with relevant information on lung deposition and its variability. Further characteristics of the studies, such as if the subjects were healthy or asthmatics, adults or children, and what device that was used, were noted. In all, 187 data points were included. Variability in lung deposition was depicted as a function of mean lung deposition; for the entire data set and for subsets thereof. Independent of device type or subject category high lung deposition was associated with low relative variability and vice versa. Using a published throat deposition model, the observed correlation of lung deposition variability to mean lung deposition could be explained as being determined largely by the extent of and variability in throat deposition. We hypothesize that throat deposition is the major determinant for lung deposition of an inhaled aerosol, and its absolute variability will largely be determined by the absolute variability in throat deposition. The relative variability in lung deposition will therefore tend to be high for low lung deposition and low for high lung deposition. Consequently, low relative variability in lung deposition can only be attained if high lung deposition is achieved.

Growth analysis and canopy architecture of velvetleaf grown under light conditions representative of irrigated Mediterranean-type agroecosystems

Velvetleaf growth and canopy architecture were compared under a range of light conditions representative of competitive and noncompetitive environments typical of irrigated Mediterranean-type agroecosystems. Velvetleaf biomass and seed production exceeded those reported in the literature. Plants grown in full light produced 1,370 g dry weight and 44,200 seeds per plant and showed low relative variability. Velvetleaf grown with corn was reduced to 21 g dry weight and 349 seeds per plant, and had high relative variability for biomass and seed numbers. Velvetleaf grown with kidney bean, intraspecific neighbors, or under shadecloth had dry weights and seed numbers that were intermediate to plants grown in full light or with corn. Relative growth rate (RGR), net assimilation rate (NAR), and leaf area ratio (LAR) were assessed utilizing Richards functions, which were fitted to the primary biomass and leaf area data by weighted regression. RGR was highest for all plants early in the season, but declined later. Dynamics of NAR and LAR appeared to be correlated with increased self-shading, shading by neighbors, leaf age, and shedding of lower canopy leaves. Dynamics of specific leaf area corresponded with light availability such that the leaves exposed to full light were thicker than those exposed to shade. The branches of plants in all treatments had random azimuths and the foliage area density was concentrated along the perimeter of the plant's canopy. Velvetleaf increased the canopy radius through extensive branching when exposed to full sunlight. Leaf area distribution and branching patterns resulted in leaf area indices of less than 1.0. Leaves maintained a perpendicular angle to the sun throughout the day, but this depended on whether leaves received a consistent directional signal from the sun and not necessarily on whether they received a high-intensity signal. When shaded, the allocation of dry matter went primarily to the stem tissue, which increased the height rather than the girth of the plants. There was a 10- to 20-d delay for allocations to seed in the case of shaded plants relative to those grown in full sunlight. In brief, velvetleaf had a wide range of growth and canopy responses to a variety of light availabilities and it should have little difficulty in becoming fully established in the irrigated agroecosystems of Mediterranean-type regions.