Dermoscopy of Small Diameter Melanomas with the Diagnostic Feasibility of Selected Algorithms—A Clinical Retrospective Multicenter Study

Objective: The aim of the study was to verify two hypotheses. The first concerned the possibility of diagnostic dermoscopic differentiation between cutaneous melanomas of the histopathological category in situ (pTis) and thin melanomas (pT1a) in terms of their diameter. The second assessed the diagnostic feasibility of two dermoscopic algorithms aiming to detect ≤ 5.0 mm-sized melanomas histopathologically confirmed as pTis and pT1a. Methods: Dermoscopic images of consecutive cases of histopathologically confirmed melanomas were evaluated by three independent investigators for the presence of the predefined criteria. The melanomas were subdivided according to their diameter into small melanomas, so-called micromelanomas (microM)—sized ≤ 5.0 mm and >5.0 mm, according to published definitions of small melanocytic lesions. The Triage Amalgamated Dermoscopic Algorithm (TADA) and the revisited 7-point checklist of dermoscopy (7-point) algorithm were chosen for the diagnostic feasibility. Odds ratios and corresponding 95% confidence limits (CL) were calculated using the logistic regression adjusted for age for the melanoma-specific dermoscopic structures, the dermoscopic patterns and the diagnostic feasibility of the 7-point checklist and TADA algorithms. The p-values of the results were corrected using the Bonferroni method. Results: In total, 106 patients with 109 melanomas, 50 sized ≤ 5.0 mm and 59 exceeding the diameter of 5.0 mm, were retrospectively analyzed. The prevalent general pattern of microM was the spitzoid one (48% vs. 11.86%, p = 0.0013). Furthermore, 40% of microM vs. 6.78% melanomas sized > 5.0 mm (p = 0.0023) did not present melanoma-specific patterns. The asymmetric multicomponent pattern was present in 64.41% melanomas sized > 5.0 mm and in 26.00% microM (p = 0.0034). The asymmetry of structures or colors was detected in 56% microM vs. 89.83% (p = 0.0020) and 56% microM and 94.92% (p = 0.000034) melanoma sized > 5.0 mm, respectively. The differences in frequency of the detected dermoscopic structures specific to melanomas revealed that microM are almost deprived of negative networks (p = 0.04), shiny white structures (p = 0.0027) and regression features (p = 0.00003). Neither prominent skin markings nor angulated lines were found in the entire study group. Out of the vascular structures, microM presented only dotted (32%) or polymorphous (28%) vessels, although more rarely than melanomas sized > 5.0 mm (66.1% p = 0.017 and 49% p > 0.05, respectively). The diagnostic feasibility revealed a score ≥ 3 of the 7-point algorithm (indicative for malignancy) in 60% microM and 98.31% melanomas sized > 5.0 mm (p = 0.000006). The TADA algorithm revealed melanoma-specific patterns in 64% microM and 96.61% > 5.0 mm-sized melanomas (p = 0.00006) and melanoma-specific structures in 72% and 91.53% (p > 0.05), respectively. Conclusion: In the dermoscopy, 40% of micromelanomas histopathologically staged as pTis and pT1a did not reveal melanoma-specific patterns. Among the general melanocytic patterns, the spitzoid one was the most frequently found in melanomas sized ≤ 5.0 mm. The 7-point checklist and TADA dermoscopic algorithms were helpful in the identification of the majority of melanomas sized ≤ 5.0 mm.

Determination of a Treatment Response Threshold for the Eosinophilic Esophagitis Endoscopic Reference Score

Background and study aims: While endoscopic features of eosinophilic esophagitis (EoE) are measured using the validated EoE Endoscopic Reference Score (EREFS), a threshold for treatment response has not been defined. We aimed to determine a cut-point for endoscopic response as measured by EREFS. Patients and Methods: We performed a secondary analysis of a randomized clinical trial comparing budesonide slurry to swallowed fluticasone multidose inhaler for initial treatment of EoE. In the parent trial, EREFS was determined before and after treatment (score range 0-9), as were histologic findings and dysphagia symptoms. We performed tabular, flexible trend, and dependent mixture analyses of measures of treatment response to select the best clinical EREFS threshold. Results: In the 111 included subjects (mean age 39 years; 67% male; 96% white), an EREFS threshold of ≤2 was 80% sensitive (95% confidence limits 69 - 88%) and 83% specific (95% confidence limits 67 - 94%) for histologic response (peak of <15 eosinophils per high-power field). Flexible trend analysis and dependent mixture modeling similarly suggested a threshold of ≤2 best captured the correlation of EREFS with histologic and symptomatic measures. Dependent mixture modeling found near total membership in the response class at EREFS of 0 or 1 and >75% at EREFS of 2 or 3. Conclusions: An EREFS of ≤2 was the best clinical threshold for endoscopic response to topical steroid treatment and was consistent with clinical and histologic response. Therefore, future studies can report a binary outcome of endoscopic response when EREFS is two or less.

Probability Analysis and Prevention of Offshore Oil and Gas Accidents: Fire as a Cause and a Consequence

Failures during the drilling and exploitation of hydrocarbons that result in catastrophic offshore oil and gas accidents are relatively rare but if they occur the consequences can be catastrophic in terms of loss of life and environmental damage. Therefore, to gain insight into their prevention, the largest major offshore oil and gas accidents, those with more than 10 fatalities or with a large environmental impact, are analyzed in this article. Special attention is placed on fire as a cause and a consequence. Relevant technological and legislative changes and updates regarding safety that have followed such accidents and that can prevent potential future similar misfortunes are evaluated. Two main approaches to safety are compared: (1) the American prescriptive vs. (2) the European goal-oriented approach. The main causes of accidents are tested statistically in respect of failure probability, where the exact confidence limits for the estimated probabilities are computed. The results of the statistical test based on exact confidence intervals show that there is no significant difference between the analysed factors, which describe the main causes of offshore oil and gas accidents. Based on the small but carefully chosen group of 24 of the largest accidents, it can be concluded that there is no evidence of a difference between the categories of the main causes of accidents.

Fast and accurate bootstrap confidence limits on genome-scale phylogenies using little bootstraps

Felsenstein's bootstrap resampling approach, applied in thousands of research articles, imposes a high computational burden for very long sequence alignments. We show that the bootstrapping of a collection of little subsamples, coupled with median bagging of subsample confidence limits, produces accurate bootstrap confidence for phylogenetic relationships in a fraction of time and memory. The little bootstraps approach will enhance rigor, efficiency, and parallelization of big data phylogenomic analyses.

A stochastic fuzzy multi-criteria group decision-making for sustainable vendor selection in Indian petroleum refining sector

PurposeThis paper aims to select key criteria for sustainable vendor assessment and spare-parts supplies in the Indian petroleum refining sector using stochastic fuzzy technique for order of preference by similarity to ideal solution (SFTOPSIS).Design/methodology/approachThe criteria for sustainable vendor evaluation and selection are identified from the review of the literature and further; it is finalized using the Delphi method. Eight supply chain (SC) experts from the Indian petro refining sector were identified as having more than five years of experience and agreed to participate in this study (known as decision-makers (DM)). Five vendors supplying spare-parts are shortlisted from the market with the discussion and consent of procurement experts from petroleum refineries. Subsequently, criteria and vendors are rated based on relative importance in linguistic terms from the group of eight DMs. As ratings involve uncertainties in the decision-making, the SFTOPSIS method is applied to determine criteria weight and vendor ranking at a distinct significance level (α). The ranking of the vendors is obtained for sustainable supply of spare-parts in the Indian petro refining sector using the SFTOPSIS method.FindingsThe ranking of sustainable vendors is obtained through the integrated application of the fuzzy and stochastic approach to capture the uncertainties in the ratings of DMs. The sensitivity analysis is carried out at distinct confidence limits of a normal distribution to obtain a robust ranking of the vendors. In this paper, a case application of SFTOPSIS in the Indian petro refining sector is presented in which key criteria and the vendor ranking are found to be changing with confidence limit for sustainable vendor evaluation.Practical implicationsThe fuzziness and randomness in relative ratings collects from a group of DMs are taken in the proposed methodology. The distinct approaches are compared with changing significance-level under stochastic, fuzzy and deterministic TOPSIS to acquire robustness in the ranking. The proposed SFTOPSIS model can be useful to practitioners from the petroleum sector.Originality/valueThe originality of the paper contributes to an application of the SFTOPSIS method that is the extension of FTOPSIS in the petro refining sector of a developing country. The sensitivity analysis with distinct significance-level shows the uncertainties in the collected ratings from the DMs that supports robustness in the ranking. It might be helpful for SC professionals from the petro refining sector, who assess the rank of the vendors at different confidence limits for sustainable supply of spare-parts. Further research in the petroleum industry from emerging economies needs to be undertaken to broaden its scope and applicability.

P–650 Body weight is the main determinant of systemic follicle stimulating hormone (FSH) concentrations during controlled ovarian stimulation with follitropin delta

Study question Which individual subject characteristics affect systemic FSH concentrations in women undergoing controlled ovarian stimulation with follitropin delta? Summary answer Body weight is the main determinant of systemic FSH concentrations. Renal function, Asian race, country/region, hepatic function and age have at most a small influence. What is known already After administration of FSH, systemic FSH concentrations are inversely related to body weight. It has been observed that the impact of body weight on ovarian response is clinically relevant at low doses but not at high doses. In patients with anti-Müllerian hormone (AMH) ≥15 pmol/L, follitropin delta is dosed according to each patient’s body weight, which influences systemic FSH concentrations, and her AMH level which predicts ovarian response. Study design, size, duration Serum FSH concentrations were assessed in five randomised, controlled, assessor-blinded, multicentre trials of follitropin delta in women undergoing an assisted reproductive technology programme. The trials were conducted in Europe, America and Asia. In all, 1.665 women treated with follitropin delta contributed to the evaluation with 4052 serum FSH concentrations, measured at steady state by an immunoassay. Participants/materials, setting, methods FSH concentrations were described with a pre-specified one-compartment population pharmacokinetic model. The key model parameters were the apparent total clearance (CL/F) of follitropin delta, the interindividual variability herein and the effects of baseline values of body weight, age, race, country/region, renal and hepatic function on CL/F. Renal function was assessed using the estimated glomerular filtration rate (eGFR) and hepatic function by alanine transaminase (ALT) and bilirubin levels. Main results and the role of chance The area under the FSH concentration-time curve during a dosing interval (AUC) was derived from dose and CL/F. Body weight was the covariate with the most pronounced effect on AUC, both in terms of the effect magnitude and statistical significance. AUC was 1.51-fold higher (90% confidence limits: 1.48; 1.54) in women with the lowest observed body weight of 40 kg compared to women with a typical body weight of 58 kg. The effect of renal function on AUC was small and in the same order of magnitude as the bioequivalence limits (0.8; 1.25). AUC was 1.28-fold higher (90% confidence limits: 1.23; 1.33) in women with the lowest observed eGFR value of 44 mL/min/1.73m2, compared to women with a typical eGFR value of 98 mL/min/1.73m2. The effects of Asian race and country/region (Japan, China, Other Asian) were confounded with each other and well within the bioequivalence limits when evaluated independently. The effects of age and the hepatic function markers ALT and bilirubin were well within the bioequivalence limits. Limitations, reasons for caution The women participating in the trials were generally healthy and the results cannot be transferred to women with renal or hepatic disease. A limited number of Black women contributed to the present analysis but the trend was similar. Data is forthcoming from ongoing trials including larger numbers of Black women. Wider implications of the findings: The findings support dosing follitropin delta by body weight and without adjustment for renal function, hepatic function, race, age or country/region. Trial registration number NCT01426386, NCT02309671, NCT01956110, NCT03228680 and NCT03296527

Statistical control charts to assess the incidence of presumably infectious diarrhea reported between 2009 and 2019 in children under 4 years of age in the macro regions of Araçatuba, Marília and Presidente Prudente, São Paulo, Brazil.

Objective: To evaluate the monthly rates of hospitalizations for childhood diarrhea in macro-regions of Araçatuba, Marília and Presidente Prudente, SP, between 2019 -June Between June 2009. Methods: The average rates and their standard deviations for admission of diarrhea in the target population were obtained from DATASUS and standardized for cases x 100,000 inhabitants. Confidence limits were established, occurrences above confidence limits were considered epidemic events. The normality of the data and serial autocorrelation were tested using the Shapiro-Wilk and Durbin-Watson method. Results: All methods detected epidemic occurrences in the three regions. Araçatuba and Marília, the peaks were concentrated in the first half of the decade and Presidente Prudente, close to the middle. The CUSUM method was more sensitive to detect epidemic periods, however the normality data and assumptions have been violated by serial autocorrelation in a few months. The EWMA method was considered the most appropriate. Conclusions: Statistical process control charts can be used to monitor and compare disease incidence between different regions.

Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system

Objectives The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. Methods Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. Results Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. Conclusions Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.