Re-evaluation of histological diagnoses of malignant mesothelioma by immunohistochemistry

<p>Abstract</p> <p>Background</p> <p>In order to provide reliable tissue material for malignant mesothelioma (MM) studies, we re-evaluated biopsies and autopsy material from 61 patients with a diagnosis of MM from the period of 1980-2002.</p> <p>Methods</p> <p>Basic positive (Calretinin, EMA, Podoplanin, Mesothelin) and negative (CEA, Ber-Ep4) immunohistochemical (IHC) marker reactions were determined. If needed, more markers were used. Histological diagnoses were made by three pathologists. Survival data were calculated.</p> <p>Results</p> <p>49 cases (80%) were considered being MM by a high degree of likelihood, five more cases possible MM. Of the remaining seven cases, three were diagnosed as adenocarcinoma, three as pleomorphic lung carcinoma, in one peritoneal case a clear entity diagnosis could not be given. One of the possible MM cases and two of the lung carcinoma cases had this already as primary diagnoses, but were registered as MM.</p> <p>With a sensitivity of 100%, Calretinin and CEA were the most reliable single markers. The amount of MM cells with positive immunoreactivity (IR) for Podoplanin and Mesothelin showed most reliable inverse relation to the degree of atypia.</p> <p>In the confirmed MM cases, there had been applied either no IHC or between one and 18 markers.</p> <p>The cases not confirmed by us had either lacked IHC (n = 1), non-specific markers were used (n = 4), IR was different (n = 1), or specific markers had not shown positive IR in the right part of the tumour cells (n = 3).</p> <p>46 of the 49 confirmed and three of the not confirmed cases had been diagnosed by us as most likely MM before IHC was carried out.</p> <p>Conclusions</p> <p>In order to use archival tissue material with an earlier MM diagnosis for studies, histopathological re-evaluation is important. In possible sarcomatous MM cases without any positive IR for positive MM markers, radiology and clinical picture are essential parts of diagnostics. IHC based on a panel of two positive and two negative MM markers has to be adapted to the differential diagnostic needs in each single case. New diagnostic tools and techniques are desirable for cases where IHC and other established methods cannot provide a clear entity diagnosis, and in order to improve MM treatment.</p

The EC-Earth3 Earth system model for the Coupled Model Intercomparison Project 6

The Earth system model EC-Earth3 for contributions to CMIP6 is documented here, with its flexible coupling framework, major model configurations, a methodology for ensuring the simulations are comparable across different high-performance computing (HPC) systems, and with the physical performance of base configurations over the historical period. The variety of possible configurations and sub-models reflects the broad interests in the EC-Earth community. EC-Earth3 key performance metrics demonstrate physical behavior and biases well within the frame known from recent CMIP models. With improved physical and dynamic features, new Earth system model (ESM) components, community tools, and largely improved physical performance compared to the CMIP5 version, EC-Earth3 represents a clear step forward for the only European community ESM. We demonstrate here that EC-Earth3 is suited for a range of tasks in CMIP6 and beyond

Quantitative responses of lake phytoplankton to eutrophication in Northern Europe

Based on the currently largest available dataset of phytoplankton in lakes in northern Europe, we quantified the responses of three major phytoplankton classes to eutrophication. Responses were quantified by modelling the proportional biovolumes of a given group along the eutrophication gradient, using generalized additive models. Chlorophyll-a (Chl-a) was chosen as a proxy for eutrophication because all classes showed more consistent responses to Chl-a than to total phosphorus. Chrysophytes often dominate in (ultra-) oligotrophic lakes, and showed a clear decrease along the eutrophication gradient. Pennate diatoms were found to be most abundant at moderate eutrophication level (spring-samples). Cyanobacteria often dominate under eutrophic conditions, especially in clearwater lakes at Chl-a levels >10 μg l−1 (late summer samples). We compare the relationships among types of lakes, based on the lake typology of the northern geographic intercalibration group, and among countries sharing common lake types. Significant differences were found especially between humic and clearwater lakes, and between low- and moderately alkaline lakes, but we could not identify significant differences between shallow and deep lakes. Country-specific differences in response curves were especially pronounced between lakes in Norway and Finland, while Swedish lakes showed an intermediate pattern, indicating that country-specific differences reflect large-scale geographic and climatic differences in the study area

Tumor angiogenesis and prognosis in squamous cell carcinoma of the head and neck

BACKGROUND: The progression of tumor growth requires the recruitment of new blood vessels. It has been suggested that the degree of neovascularization would correlate with clinical prognosis. The purpose of the present study was to ascertain whether tumor vascularization correlated with clinical outcome in cases of primary squamous cell carcinoma of the head and neck (SCCHN).METHODS: In tumor biopsies from 48 patients, microvessel density was determined by immunohistochemistry based on polyclonal antibodies against factor VIII related endothelial antigen. Computerized image analysis was used to evaluate the staining intensity per histologic area. The degree of staining was quantitated and expressed as microvessel density, low and high microvessel density subgroups being compared with regard to survival.RESULTS: Median survival was 10 months in the subgroup with very low microvessel density scores, as contrasted to 69 months in the remainder with high scores (p = 0.08). Neither the patient's age, TNM status, clinical stage, nor histologic grade was related to microvessel density. Among the patients who eventually died of SCCHN (n = 23), there was a subgroup of patients with complete response to radiotherapy. This subgroup had significantly higher microvessel density and longer survival than did the patients who responded poorly or not at all to radiotherapy.CONCLUSION: The findings suggest that in SCCHN the degree of vascularization might be used as a predictor of response to radiotherapy

Comparing ERA-Interim clouds with satellite observations using a simplified satellite simulator

An evaluation of the ERA-Interim clouds using satellite observations is presented. To facilitate such an evaluation in a proper way, a simplified satellite simulator has been developed and applied to 6-hourly ERA-Interim reanalysis data covering the period of 1982 to 2014. The simulator converts modelled cloud fields, for example those of the ERA-Interim reanalysis, to simulated cloud fields by accounting for specific characteristics of passive imaging satellite sensors such as the Advanced Very High Resolution Radiometer (AVHRR), which form the basis of many long-term observational datasets of cloud properties. It is attempted to keep the simulated cloud fields close to the original modelled cloud fields to allow a quality assessment of the latter based on comparisons of the simulated clouds fields with the observations. Applying the simulator to ERA-Interim data, this study firstly focuses on the spatial distribution and frequency of clouds (total cloud fraction) and on their vertical position, using cloud-top pressure to express the cloud fraction of high-level, mid-level and low-level clouds. Furthermore, the cloud-top thermodynamic phase is investigated. All comparisons incorporate knowledge of systematic uncertainties in the satellite observations and are further stratified by accounting for the limited sensitivity of the observations to clouds with very low cloud optical thickness (COT). The comparisons show that ERA-Interim cloud fraction is generally too low nearly everywhere on the globe except in the polar regions. This underestimation is caused by a lack of mid-level and/or low-level clouds, for which the comparisons only show a minor sensitivity to the cloud optical thickness thresholds applied. The amount of ERA-Interim high-level clouds, being higher than in the observations, agrees with the observations within their estimated uncertainties. Removing the optically very thin clouds (COT&thinsp;&lt;0.15) from the model fields improves the agreement with the observations for high-level cloud fraction locally (e.g. in the tropics), while for the mid-latitude regions, the best agreement for high-level cloud fraction is found when removing all clouds with COT&thinsp;&lt;1.0. Comparisons of the cloud thermodynamic phase at the cloud top reveal a too high relative ice cloud frequency in ERA-Interim, being most pronounced in the higher latitudes. Indications are found that this is due to the suppression of liquid cloud occurrence for temperatures below −23&thinsp;∘C in ERA-Interim. The application of this simulator facilitates a more effective use of passive satellite observations of clouds in the evaluation of modelled cloudiness, for example in reanalyses.</p