Intraclass correlation coefficients (ICC) are recommended for the assessment of the reliability of measurement scales. However, the ICC is subject to a variety of statistical assumptions such as ...normality and stable variance, which are rarely considered in health applications.
A Bayesian approach using hierarchical regression and variance-function modeling is proposed to estimate the ICC with emphasis on accounting for heterogeneous variances across a measurement scale. As an application, we review the implementation of using an ICC to evaluate the reliability of Observer OPTION
, an instrument which used trained raters to evaluate the level of Shared Decision Making between clinicians and patients. The study used two raters to evaluate recordings of 311 clinical encounters across three studies to evaluate the impact of using a Personal Decision Aid over usual care. We particularly focus on deriving an estimate for the ICC when multiple studies are being considered as part of the data.
The results demonstrate that ICC varies substantially across studies and patient-physician encounters within studies. Using the new framework we developed, the study-specific ICCs were estimated to be 0.821, 0.295, and 0.644. If the within- and between-encounter variances were assumed to be the same across studies, the estimated within-study ICC was 0.609. If heteroscedasticity is not properly adjusted for, the within-study ICC estimate was inflated to be as high as 0.640. Finally, if the data were pooled across studies without accounting for the variability between studies then ICC estimates were further inflated by approximately 0.02 while formerly allowing for between study variation in the ICC inflated its estimated value by approximately 0.066 to 0.072 depending on the model.
We demonstrated that misuse of the ICC statistics under common assumption violations leads to misleading and likely inflated estimates of interrater reliability. A statistical analysis that overcomes these violations by expanding the standard statistical model to account for them leads to estimates that are a better reflection of a measurement scale's reliability while maintaining ease of interpretation. Bayesian methods are particularly well suited to estimating the expanded statistical model.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To dissect the tumor ecosystem following immune checkpoint blockades (ICBs) in intrahepatic cholangiocarcinoma (ICC) at a single-cell level.
Single-cell RNA sequencing (scRNA-seq) data of 10 ICC ...patients for the ICB clinical trial were extracted from GSE125449 and systematically reanalyzed. Bulk RNA-seq data of 255 ICC patients were analyzed. Infiltration levels of SPP1
CD68
tumor-associated macrophages (TAMs) were examined by dual immunofluorescence (IF) staining in 264 resected ICC samples. The correlation between SPP1
TAMs and clinicopathological features as well as their prognostic significance was evaluated.
Among the 10 patients, five received biopsy at baseline, and others were biopsied at different timings following ICBs. Single-cell transcriptomes for 5,931 cells were obtained. A tighter cellular communication network was observed in ICB-treated ICC. We found a newly emerging VEGF signaling mediated by PGF-VEGFR1 between cancer-associated fibroblasts (CAFs) and endothelial cells in ICC following ICBs. SPP1 expression was dramatically upregulated, and SPP1
TAM gene signatures were enriched in TAMs receiving ICB therapy. We also identified SPP1
TAMs as an independent adverse prognostic indicator for survival in ICC.
Our analyses provide an overview of the altered tumor ecosystem in ICC treated with ICBs and highlight the potential role of targeting CAFs and SPP1
TAMs in developing a more rational checkpoint blockade-based therapy for ICC.
Background & Aims Chronic unexplained nausea and vomiting (CUNV) is a debilitating disease of unknown cause. Symptoms of CUNV substantially overlap with those of gastroparesis, therefore the diseases ...may share pathophysiologic features. We investigated this hypothesis by quantifying densities of interstitial cells of Cajal (ICCs) and mapping slow-wave abnormalities in patients with CUNV vs controls. Methods Clinical data and gastric biopsy specimens were collected from 9 consecutive patients with at least 6 months of continuous symptoms of CUNV but normal gastric emptying who were treated at the University of Mississippi Medical Center, and from 9 controls (individuals free of gastrointestinal disease or diabetes). ICCs were counted and ultrastructural analyses were performed on tissue samples. Slow-wave propagation profiles were defined by high-resolution electrical mapping (256 electrodes; 36 cm2 ). Results from patients with CUNV were compared with those of controls as well as patients with gastroparesis who were studied previously by identical methods. Results Patients with CUNV had fewer ICCs than controls (mean, 3.5 vs 5.6 bodies/field, respectively; P < .05), with mild ultrastructural abnormalities in the remaining ICCs. Slow-wave dysrhythmias were identified in all 9 subjects with CUNV vs only 1 of 9 controls. Dysrhythmias included abnormalities of initiation (stable ectopic pacemakers, unstable focal activities) and conduction (retrograde propagation, wavefront collisions, conduction blocks, and re-entry), operating across bradygastric, normal (range, 2.4–3.7 cycles/min), and tachygastric frequencies; dysrhythmias showed velocity anisotropy (mean, 3.3 mm/s longitudinal vs 7.6 mm/s circumferential; P < .01). ICCs were less depleted in patients with CUNV than in those with gastroparesis (mean, 3.5 vs 2.3 bodies/field, respectively; P < .05), but slow-wave dysrhythmias were similar between groups. Conclusions This study defined cellular and bioelectrical abnormalities in patients with CUNV, including the identification of slow-wave re-entry. Pathophysiologic features of CUNV were observed to be similar to those of gastroparesis, indicating that they could be spectra of the same disorder. These findings offer new insights into the pathogenesis of CUNV and may help to inform future treatments.
Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer products, which contributes to widespread exposure of humans. OPE diester metabolites in urine have been ...used as biomarkers of human exposure to these chemicals. Little is known, however, about occurrence and temporal variability in urinary concentrations of OPE metabolites in humans. In this study, 11 OPE metabolites were measured in 213 urine samples collected from 19 volunteers from Albany, New York, United States, at 3-day intervals for five weeks to investigate temporal variability in urinary concentrations. Diphenyl phosphate (DPHP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the major OPE metabolites, detected in all urine samples at specific gravity (SG)-adjusted concentrations (geometric mean, GM) of 1060 and 414 pg/mL and creatinine (Cr)-adjusted concentration (GM) of 404 and 156 ng/g, respectively. Inter-day variability in urinary OPE metabolite concentrations in 19 individuals was evaluated by intraclass correlation coefficients (ICCs). The inter-day variability in Cr-adjusted OPE metabolite concentrations (ICC: 0.31–0.67) was lower than those of SG-adjusted (ICC: 0.19–0.71) and unadjusted urinary concentrations (ICC: 0.24–0.74). BDCIPP (ICC: 0.68) and bis(2-chloroethyl) phosphate (BCEP) (ICC: 0.67) concentrations showed a moderate-to-high reliability over the sampling period, whereas the other nine OPE metabolites exhibited a moderate reliability (ICC: 0.31–0.55). Urine samples were further stratified by gender, age, ethnicity, and body mass index (BMI). The concentrations of BDCIPP and DPHP were significantly lower in males with normal BMI (BMI: 18.5–25 kg/m2) than in females and other BMI categories (p < 0.01). Relatively high ICCs, indicating low inter-day variability, were observed for males (ICC: 0.35–0.71) of 30–40 years of age (ICC: 0.34–0.87) with normal BMI (ICC: 0.28–0.64). The daily exposure doses to OPEs were estimated from urinary concentrations of corresponding OPE metabolites. The estimated doses of triphenyl phosphate (TPHP) and triethyl phosphate (TEP), based on median urinary concentrations of their metabolites, were 19.4 and 24.0 ng/kg bw/day, and the exposure dose to ∑OPEs was estimated at 65.3 ng/kg bw/day. Overall, our results indicate a high ICC for Cr-adjusted urinary concentrations of 11 OPE metabolites in urine.
•Interday variability in urinary concentrations of OPE metabolites was studied.•Diphenyl phosphate and bis(1,3-dichloro-2-propyl) phosphate were the major OPE metabolites in urine.•Urine collected longitudinally for five weeks from volunteers showed moderate variability.•Creatinine adjustment of urinary OPE metabolite levels improved ICC and increased reproducibility.•Age, gender, race and BMI had some effects on ICC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite their known carcinogenic potential, primary aromatic amines (AAs) continue to be used in various consumer products. Human exposure to AAs is a subject of current concern. Although urinary ...measurements are used in the assessment of exposure, little is known about within- and between-individual temporal variability in urinary concentrations of AAs. In this study, we determined the concentrations of 30 AAs, nicotine and cotinine in 213 first morning void (FMV) urine samples collected longitudinally for over a five-week period from 15 participants residing in the Albany area of New York State, USA. Eight AAs, namely, aniline, 2-naphthylamine (2-NA), p-cresidine (p-CD), p-toluidine (p-TD), o/m-toluidine (o/m-TD), 4-chloroaniline (4-CA), 4,4′-methylenedi-o-toluidine (4,4’-MDA), and 2,6-dimethylaniline (2,6-DMA) were found in urine at a detection frequency (DF) in the range of 68–100%. Aniline and 2,6-DMA were the predominant compounds found at median concentrations of 6.0 and 3.81 ng/mL, respectively. Intraclass correlation coefficients (ICCs) of all urinary AA concentrations, except for 4-CA, showed moderate to poor predictability (ICC values ranged 0.248–0.697). Gender and ethnicity-related variations in ∑8AA concentrations were significant. Spearman's correlations among AA concentrations suggested that the sources of exposure were not related to tobacco smoke. No significant correlations existed between AAs concentrations and oxidative stress biomarkers (OSBs). The estimated daily intakes of AAs calculated based on urinary concentrations were several orders of magnitude below the tolerable daily intakes.
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•Temporal variability in urinary concentrations of aromatic amines was studied.•30 AAs were measured in urine collected longitudinally for 5 weeks from 15 participants.•Aniline and 2,6-dimethylaniline were the major AAs found in urine.•ICC values of AAs showed moderate to poor predictability.•Estimated daily intakes of AAs were several orders of magnitude below TDI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Radiomics research is rapidly growing in recent years, but more concerns on radiomics reliability are also raised. This review attempts to update and overview the current status of radiomics ...reliability research in the ever expanding medical literature from the perspective of a single reliability metric of intraclass correlation coefficient (ICC). To conduct this systematic review, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. After literature search and selection, a total of 481 radiomics studies using CT, PET, or MRI, covering a wide range of subject and disease types, were included for review. In these highly heterogeneous studies, feature reliability to image segmentation was much more investigated than reliability to other factors, such as image acquisition, reconstruction, post-processing, and feature quantification. The reported ICCs also suggested high radiomics feature reliability to image segmentation. Image acquisition was found to introduce much more feature variability than image segmentation, in particular for MRI, based on the reported ICC values. Image post-processing and feature quantification yielded different levels of radiomics reliability and might be used to mitigate image acquisition-induced variability. Some common flaws and pitfalls in ICC use were identified, and suggestions on better ICC use were given. Due to the extremely high study heterogeneities and possible risks of bias, the degree of radiomics feature reliability that has been achieved could not yet be safely synthesized or derived in this review. More future researches on radiomics reliability are warranted.
Despite dramatic improvements in water treatment technologies in developed countries, waterborne viruses are still associated with many of cases of illness each year. These illnesses include ...gastroenteritis, meningitis, encephalitis, and respiratory infections. Importantly, outbreaks of viral disease from waters deemed compliant from bacterial indicator testing still occur, which highlights the need to monitor the virological quality of water. Human adenoviruses are often used as a viral indicator of water quality (faecal contamination), as this pathogen has high UV-resistance and is prevalent in untreated domestic wastewater all year round, unlike enteroviruses and noroviruses that are often only detected in certain seasons. Standard methods for recovering and measuring adenovirus numbers in water are lacking, and there are many variations in published methods. Since viral numbers are likely under-estimated when optimal methods are not used, a comprehensive review of these methods is both timely and important. This review critically evaluates how estimates of adenovirus numbers in water are impacted by technical manipulations, such as during adenovirus concentration and detection (including culturing and polymerase-chain reaction). An understanding of the implications of these issues is fundamental to obtaining reliable estimation of adenovirus numbers in water. Reliable estimation of HAdV numbers is critical to enable improved monitoring of the efficacy of water treatment processes, accurate quantitative microbial risk assessment, and to ensure microbiological safety of water.
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•Concentration and detection methods for human adenovirus (HAdV) are evaluated.•Methods chosen affect the accuracy of enumerating HAdV in water.•HAdV culture analyses using non-permissive lines are underestimating numbers.•HAdV qPCR performs favourably for water quality monitoring and risk assessment.•Quantitative PCR provides capacity for early notification of water contamination.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Public health is threatened by deteriorated water quality due to bacterial regrowth and uncontrolled growth-related problems in drinking water distribution systems (DWDSs). To investigate the scope ...of this problem, a two-year field study was conducted in south China. The amount of assimilable organic carbon (AOC), total cell concentrations (TCC), and intact cell concentrations (ICC) of water samples were determined by flow cytometry. The results indicated that ICC was significantly correlated to AOC concentration when the chlorine concentration was less than 0.15 mg/L, and ICC was lower at chlorine concentrations greater than 0.15 mg/L, suggesting that free chlorine level had effect on AOC and ICC. To further analyze the effect of disinfectant on AOC and bacterial growth, we designed an orthogonal experiment with different dosages of two commonly used disinfectants, chlorine and chloramine. The results demonstrated that high concentrations of free chlorine (＞0.15 mg/L) and chloramine (＞0.4 mg/L) were associated with relatively low proportions of intact cells and cultivable bacteria. Compared with chlorine, chloramine tended to cause lower AOC level and intact cells, likely because the chlorinated disinfection byproducts (DBPs) were more easily absorbed by bacteria than the chloraminated DBPs. Based on the statistical analysis of 240 water samples, ICC was limited when AOC concentration was less than 135 μg/L, while temperature and the number of small-size particles showed positive effects on ICC (P＜0.05). We conclude that the use of chloramine and controlling particle numbers should be suitable strategies to limit bacterial regrowth.
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•Only with chlorine less than 0.15 mg/L, ICC was significantly correlated to AOC.•Cl2 above 0.15 mg/L or NH2Cl above 0.4 mg/L was associated with low ICC proportion.•Chloramine tended to cause lower AOC level and intact cells proportions.•ICC was found to be limited when AOC was less than 135 μg/L.•Particles control and use of chloramine were proper ways to limit bacterial growth.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We report on a terrestrial gamma ray flash (TGF) that occurred on 15 August 2014 coincident with an altitude‐triggered lightning at the International Center for Lightning Research and Testing (ICLRT) ...in North Central Florida. The TGF was observed by a ground‐level network of gamma ray, close electric field, distant magnetic field, Lightning Mapping Array (LMA), optical, and radar measurements. Simultaneous gamma ray and LMA data indicate that the upward positive leader of the triggered lightning flash induced relativistic runaway electron avalanches when the leader tip was at about 3.5 km altitude, resulting in the observed TGF. Channel luminosity and electric field data show that there was an initial continuous current (ICC) pulse in the lightning channel to ground during the time of the TGF. Modeling of the observed ICC pulse electric fields measured at close range (100–200 m) indicates that the ICC pulse current had both a slow and fast component (full widths at half maximum of 235 μs and 59 μs) and that the fast component was more or less coincident with the TGF, suggesting a physical association between the relativistic runaway electron avalanches and the ICC pulse observed at ground. Our ICC pulse model reproduces moderately well the measured close electric fields at the ICLRT as well as three independent magnetic field measurements made about 250 km away. Radar and LMA data suggest that there was negative charge near the region in which the TGF was initiated.
Key Points
Best documented TGF observed at ground
Second TGF induced by triggered lightning
An ICC pulse occurred simultaneously (within 20 μs) of the TGF
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
To evaluate the ability of volumetric quantitative apparent diffusion coefficient (ADC) histogram parameters and LI-RADS categorization to distinguish hepatocellular carcinoma (HCC) from ...other primary liver cancers intrahepatic cholangiocarcinoma (ICC) and combined HCC-ICC.
Methods
Sixty-three consecutive patients (44 M/19F; mean age 62 years) with primary liver cancers and pre-treatment MRI including diffusion-weighted imaging (DWI) were included in this IRB-approved single-center retrospective study. Tumor type was categorized pathologically. Qualitative tumor features and LI-RADS categorization were assessed by 2 independent observers. Lesion volume of interest measurements (VOIs) were placed on ADC maps to extract first-order radiomics (histogram) features. ADC histogram metrics and qualitative findings were compared. Binary logistic regression and AUROC were used to assess performance for distinction of HCC from ICC and combined tumors.
Results
Sixty-five lesions (HCC,
n
= 36; ICC,
n
= 17; and combined tumor,
n
= 12) were assessed. Only enhancement pattern (
p
< 0.015) and capsule were useful for tumor diagnosis (
p
< 0.014). ADC 5th/10th/95th percentiles were significant for discrimination between each tumor types (all
p
values < 0.05). Accuracy of LI-RADS for HCC diagnosis was 76.9% (
p
< 0.0001) and 69.2% (
p
= 0.001) for both observers. The combination of male gender, LI-RADS, and ADC 5th percentile yielded an AUROC/sensitivity/specificity/accuracy of 0.90/79.3%/88.9%/81.5% and 0.89/86.2%/77.8%/80.0% (all
p
values < 0.027) for the diagnosis of HCC compared to ICC and combined tumors for both observers, respectively.
Conclusion
The combination of quantitative ADC histogram parameters and LI-RADS categorization yielded the best prediction accuracy for distinction of HCC compared to ICC and combined HCC-ICC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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