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This review covers the various new markers in the literature, highlights their advantages and limitations, and suggests morphology/site specific combinations that can produce sensitivities in the 80% to 90% (and perhaps higher) range. At present only BRCA-1 related protein-1 and methylthioadenosine phosphorylase IHC, and cyclin-dependent kinase inhibitor 2A (p16) FISH have sufficient publications and reproducibility of results to be considered as established markers. CPI-455 in vitro 5-Hydroxymethyl cytosine, enhancer of zeste homolog 2, cyclin D1, and programmed death-ligand 1 IHC, and NF2 FISH are all potentially useful but need further study. The newly described entity of malignant mesothelioma in situ sits at the interface of benign and malignant mesothelial process; criteria for this diagnosis are reviewed.Vulvar high-grade neuroendocrine carcinomas (HGNECs) are rare and primarily thought to represent Merkel cell carcinoma (MCC). We present the clinicopathologic features of 16 such cases, the largest series to date. Patients were most often White, postmenopausal, and symptomatic from a palpable vulvar mass/nodule. Tumors ranged from 0.7 to 6 cm and most commonly involved the labium majus. Majority of the cases were pure HGNECs (15/16) with small cell (SC) morphology (14/16); 2 were large cell neuroendocrine carcinomas, of which 1 was combined with moderately differentiated adenocarcinoma. All tumors expressed synaptophysin. Of the 14 HGNECs with SC morphology, 6 were CK20-positive MCCs with characteristic CAM5.2 and neurofilament (NF) expression. Five of these MCCs were positive for Merkel cell polyoma virus large T-antigen (MCPyVLTAg). In contrast, 6 HGNECs with SC morphology were negative for CK20, NF, and MCPyVLTAg and classified as SCNECs. High-risk human papilloma virus was positive in all SCNECs and negatper identification of vulvar HGNECs is critical for patient management.Observational data are increasingly used with the aim of estimating causal effects of treatments, through careful control for confounding. Marginal structural models estimated using inverse probability weighting (MSMs-IPW), like other methods to control for confounding, assume that confounding variables are measured without error. The average treatment effect in an MSM-IPW may however be biased when a confounding variable is error prone. Using the potential outcome framework, we derive expressions for the bias due to confounder misclassification in analyses that aim to estimate the average treatment effect using an marginal structural model estimated using inverse probability weighting (MSM-IPW). We compare this bias with the bias due to confounder misclassification in analyses based on a conditional regression model. Focus is on a point-treatment study with a continuous outcome. Compared with bias in the average treatment effect in a conditional model, the bias in an MSM-IPW can be different in magnitude but is equal in sign. Also, we use a simulation study to investigate the finite sample performance of MSM-IPW and conditional models when a confounding variable is misclassified. Simulation results indicate that confidence intervals of the treatment effect obtained from MSM-IPW are generally wider, and coverage of the true treatment effect is higher compared with a conditional model, ranging from overcoverage if there is no confounder misclassification to undercoverage when there is confounder misclassification. Further, we illustrate in a study of blood pressure-lowering therapy, how the bias expressions can be used to inform a quantitative bias analysis to study the impact of confounder misclassification, supported by an online tool.

Animal experiment findings suggest that high doses of ionizing radiation exposure (>1.0 Gy) may cause genetic and epigenetic effects in offspring. However, epidemiological studies of offspring of radiation-exposed parents did not find increased risks of any health effects. Findings of cellular/experimental investigations and studies of human health effects are contradicting, and further investigations are needed to help resolve ambiguities using updated and/or improved data. This paper provides a detailed description of a database of families of workers of the first Russian nuclear facility, Mayak Production Association, located in the Southern Urals in the Chelyabinsk region close to Ozyorsk city, which started its operation in 1948 and today consists of reactors, radiochemical and plutonium production plants, and auxiliary facilities. The Mayak worker cohort includes 22,377 individuals (25% females) who were hired at one of the main Mayak PA facilities between 1948 and 1982 and were externally or intercteristics are presented in this paper. Examples of potential applications of the database for investigations of non-targeted and transgenerational radiation effects in offspring of exposed parents are discussed.Gallium-68 (Ga)-PSMA and F-Choline are two radionuclides that have already shown high potential for the detection of prostate cancer. The comparison between these two radionuclides has several advantages in radiation protection. The aim of this prospective study was to identify which of these two radionuclides can help in predicting the equivalent dose using the maximum standard uptake value (SUVmax) of normal organs, the kidneys. Two groups of 40 patients (total n = 80) who underwent PET/CT using Ga or F for diagnosis of prostate cancer between April 2018 and December 2018 at the American University of Beirut Medical Center were included. First, the dose rates were measured after 1 h of radionuclide uptake at 1 m distance with background of 0.015 μSv h. Then, SUVmax for kidneys were determined from images obtained with PET/CT 1 h after injection of both radionuclides. The ratios of the equivalent doses to the SUVmax for kidneys were compared for both Ga-PSMA and F-Choline. There is a positive moderate relationship between the SUVmax for kidneys and the Ga dose rate after 1 h of injection at 1 m distance from the abdomen (p-value = 0.023 0.05). This relationship is not statistically significant. This leads to the suggestion that we can predict the equivalent dose due to Ga by indicating the SUVmax from the PET/CT images.

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