Validation and improvement of Risk-UE LM2 capacity curves for URM buildings with stiff floors and RC shear walls buildings

This paper addresses seismic vulnerability assessment at an urban scale and more specifically the capacity curves involved for building damage prediction. Standard capacity curves are a function of predefined building typology and are proposed in the Risk-UE LM2 method for computation of the corresponding damage grades. However, these capacity curves have been mainly developed for building stock of southern European cities and the accuracy of their application with different building features, such as the ones of cities of northern Europe should be assessed. A recent research project of seismic scenarios for the cities of Sion and Martigny in Switzerland provided the opportunity to check the capacity curves of Risk-UE LM2 method. Within the framework of this project, a detailed analysis was achieved for more than 500 buildings. These buildings were typical Swiss buildings and were composed of both unreinforced masonry buildings with stiff floors and reinforced concrete buildings. The construction drawings of each building were collected in order to have the most accurate information about their main structural characteristics. The typological classification that has been adopted was developed in a recent research project. Based on the individual features of the buildings, individual capacity curves were defined. Results of the seismic assessment applied to the 500 buildings compare very well with those obtained by using Risk-UE LM2 method for unreinforced masonry buildings with stiff floors. A slight improvement may be proposed for buildings with three stories through their introduction to the category of low-rise instead of mid-rise buildings. By contrast, accuracy for reinforced concrete buildings with shear walls is very poor. Damage prediction using related capacity curves of Risk-UE LM2 method does not correspond to reality. Prediction is too pessimistic and moreover damage grades increase with the height category (low-rise, mid-rise and high-rise) of these buildings which is in contradiction with the observed damages for this type of buildings. Improvements are proposed to increase the accuracy of the seismic vulnerability assessment for northern European building stock. For unreinforced masonry buildings, a slight modification of the limits of the height category of buildings using the ones defined for RC buildings improves the damage prediction. For reinforced concrete buildings with shear walls improved capacity curves derived from the typological curves of the specific typology C are proposed

MiR-21 up-regulation in ampullary adenocarcinoma and its pre-invasive lesions

Poor information is available on the molecular landscape characterizing the carcinogenetic process leading to ampullary carcinoma. MiR-21 is one of the most frequently up-regulated miRNAs in pancreatic adenocarcinoma, a tumor sharing similar molecular features with ampullary adenocarcinomas (AVCs), above all with the pancreatic-biliary type. We profiled, by in situ hybridization (ISH), miR-21 expression in a series of 26 AVCs, 50 ampullary dysplastic lesions (35 low-grade [LG-IEN] and 15 high-grade [HG-IEN]) and 10 normal duodenal mucosa samples. The same series was investigated by immunohistochemistry for β-catenin, p53 and HER2 expression. HER2 gene amplification was evaluated by chromogenic in situ hybridization. To validate miR-21 ISH results we performed miR-21 qRT-PCR analysis in a series of 10 AVCs and their matched normal samples. All the normal control samples showed a negative or faint miR-21 expression, whereas a significant miR-21 up-regulation was observed during the carcinogenetic cascade (p < 0.001), with 21/26 (80.8%) of cancer samples showing a miR-21 overexpression. In comparison to control samples, a significant overexpression was found in samples of LG-IEN (p = .0003), HG-IEN (p = .0001), and AVCs (p < 0.0001). No significant difference in miR-21 overexpression was observed between LG-IEN, HG-IEN and AVCs. By qRT-PCR analysis, AVCs showed a 1.7-fold increase over the controls (p = .003). P53 was frequently dysregulated in both dysplastic and carcinoma samples (44 out of 76; 57.9%). A 20% (10/50) of dysplastic lesions and 11% (3/26) of carcinomas were characterized by a nuclear localization of β-catenin. Only 2 AVCs (7.7%; both intestinal-type) showed a HER2 overexpression (both 2+), which corresponded to a HER2 gene amplification at CISH analysis. This is the first study demonstrating a miRNA dysregulation in the whole spectrum of ampullary carcinogenesis. MiR-21 overexpression is an early molecular event during ampullary carcinogenesis and its levels increase with the neoplastic progression

The Italian Rare Pancreatic Exocrine Cancer Initiative

INTRODUCTION: Exocrine pancreatic cancers include common type pancreatic ductal adenocarcinoma and cystic neoplasms, which account for 85% and 10% of cases, respectively. The remaining 5% are rare histotypes, comprising adenosquamous carcinoma, acinar cell carcinoma, signet ring cell carcinoma, medullary carcinoma, pancreatoblastoma, hepatoid carcinoma, undifferentiated carcinoma and its variant with osteoclast-like giant cells, solid pseudopapillary carcinoma, and carcinosarcoma. Due to their low incidence, little knowledge is available on their clinical and molecular features as well as on treatment choices. The national initiative presented here aims at the molecular characterization of series of rare histotypes for which therapeutic and follow-up data are available. METHODS: A nationwide Italian Rare Pancreatic Cancer (IRaPaCa) task force whose first initiative is a multicentric retrospective study involving 21 Italian cancer centers to retrieve histologic material and clinical and treatment data of at least 100 patients with rare exocrine pancreatic cancers has been created. After histologic revision by a panel of expert pathologists, DNA and RNA from paraffin tissues will be investigated by next-generation sequencing using molecular pathway-oriented and immune-oriented mutational and expression profiling panels constructed availing of the information from the International Cancer Genome Consortium. Bioinformatic analysis of data will drive validation studies by immunohistochemistry and in situ hybridization, as well as nanostring assays. CONCLUSIONS: We expect to gather novel data on rare pancreatic cancer types that will be useful to inform the design of therapeutic choices