The Restoration Interventions of “Forte Marghera” in Venice

In the framework of the Strategic Masterplan Cultural Heritage 2014-2018 of the Italian Ministry of Culture, a specific attention for the strengthening and constitution of relevant urban cultural centers is sought through the restoration and re-use of structural complexes of great architectural and historic value such as the case of Forte Marghera (Marghera Fort) of Venice. The need to build a fortress at the point where the mainland approached Venice was understood, after the fall of the “Serenissima” Republic (1797), by the Austrian Empire. The fort was therefore built in a marshy area on the edge of the Venice lagoon, crossed by a maze of canals. The works started in 1805. On the area there was already the old village of Malghera, home to warehouses and customs, which was incorporated into the Fort. However, the return of Napoleon's troops in 1806 surprised the works still in a early stage. The fortified work was then revised according to the plans of the French architect Marescò and conducted under the guidance of the general and military engineer François-Joseph Chaussegros de Léry and later the Chasseloup. The most significant buildings still present in the fortress – object of the current restoration works - are the two French barracks (1805-1814), located on the front near the dock. They are two-storey brickwork masonry structures with a 83x15 m rectangular plan and perimeter walls reaching a 3 m thickness, provided with decorative elements made of Istria stone. Visible decay is present in both two massive buildings, due to differential settlements mainly visible the long sides of both buildings, especially affecting the West one, also partially subjected to local collapse. A wide investigation campaign, aiming to the adequate characterization of the constituting materials and building techniques, was carried out in order to properly feed the design of conservative restoration interventions. Results indicate the use of good quality materials and proper layout also in the foundation system, indicating in the poor soil mechanical characteristics the main structural deficiency leading to the visible settlements. To date, the detailed design stage was reached for just one of the three buildings involved in the restoration, while the two remaining buildings are still in a preliminary design phase

Serum DU-PAN-2 in the differential diagnosis of pancreatic cancer: influence of jaundice and liver dysfunction.

The usefulness of serum DU-PAN-2 in diagnosing pancreatic cancer and in distinguishing between this cancer and other benign and malignant diseases, and to assess the role of liver dysfunction in altering the serum levels of this marker were investigated. DU-PAN-2 was measured in the sera of 31 patients with pancreatic cancer, 32 with chronic pancreatitis, 20 with benign and 21 with malignant extra-pancreatic diseases. DU-PAN-2 was found to be above 300 U ml-1 in 21/31 patients with pancreatic cancer (sensitivity 68%). Only 3/32 patients with chronic pancreatitis had abnormal values. A substantial number of patients with both benign and malignant extra-pancreatic diseases had an elevated serum DU-PAN-2 (9/20 and 15/21, respectively). Correlations were found between DU-PAN-2 and (1) total bilirubin, (2) alanine-amino-transferase and (3) alkaline phosphatase. Of the patients with high DU-PAN-2 values, jaundice was found in: 2/3 with chronic pancreatitis, 9/10 with benign and 12/14 with malignant extra-pancreatic diseases. In conclusion, the serum DU-PAN-2 test for pancreatic malignancy is not completely satisfactory, because it is not sensitive enough. While the test for chronic pancreatitis has an acceptable specificity, the assay cannot distinguish between pancreatic cancer and other extra-pancreatic diseases, mainly of the liver and biliary tract. Liver dysfunction as well as jaundice seem to considerable affect the levels of this marker, as reported elsewhere for CA 19-9

Alteration of the serum levels of the epidermal growth factor receptor and its ligands in patients with non-small cell lung cancer and head and neck carcinoma

Serum levels of the soluble epidermal growth factor receptor (sEGFR) and its ligands epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and amphiregulin (AR) were measured in healthy donors and patients with non-small cell lung cancer (NSCLC) and head and neck carcinoma (HNC). In NSCLC, we found sEGFR and EGF levels significantly lowered in patients with respect to healthy donors. In HNC patients, significantly diminished levels were found in the case of sEGFR, EGF and also AR. In both malignancies, no significant association was found between the serum levels of the molecules and the patients' gender, age or smoking habit. Only a significant association was found between the decrease of sEGFR and the absence of distant metastasis in NSCLC and the tumour stage in HNC. The most interesting result was that combining sEGFR and EGF, sensitivities of 88% in NSCLC and 100% in HNC were reached without losing specificity (97.8% in both cases). The use of discriminant analysis and logistic regression improved the sensitivity for NSCLC and the specificity for HNC. These data demonstrate a potentially interesting value of the serum levels of sEGFR and EGF, especially when combined, as markers for NSCLC and HNC

Migration rules: tumours are conglomerates of self-metastases

Tumours are heterogeneous populations composed of different cells types: stem cells with the capacity for self-renewal and more differentiated cells lacking such ability. The overall growth behaviour of a developing neoplasm is determined largely by the combined kinetic interactions of these cells. By tracking the fate of individual cancer cells using agent-based methods in silico, we apply basic rules for cell proliferation, migration and cell death to show how these kinetic parameters interact to control, and perhaps dictate defining spatial and temporal tumour growth dynamics in tumour development. When the migration rate is small, a single cancer stem cell can only generate a small, self-limited clone because of the finite life span of progeny and spatial constraints. By contrast, a high migration rate can break this equilibrium, seeding new clones at sites outside the expanse of older clones. In this manner, the tumour continually ‘self-metastasises'. Counterintuitively, when the proliferation capacity is low and the rate of cell death is high, tumour growth is accelerated because of the freeing up of space for self-metastatic expansion. Changes to proliferation and cell death that increase the rate at which cells migrate benefit tumour growth as a whole. The dominating influence of migration on tumour growth leads to unexpected dependencies of tumour growth on proliferation capacity and cell death. These dependencies stand to inform standard therapeutic approaches, which anticipate a positive response to cell killing and mitotic arrest

Neurotensin Receptor 1 Is Expressed in Gastrointestinal Stromal Tumors but Not in Interstitial Cells of Cajal

Gastrointestinal stromal tumors (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the KIT or PDGFRA receptor tyrosine kinases are present in the majority of GIST, leading to ligand-independent activation of the intracellular signal transduction pathways. We previously investigated the gene expression profile in the murine KitK641E GIST model and identified Ntsr1 mRNA, encoding the Neurotensin receptor 1, amongst the upregulated genes. Here we characterized Ntsr1 mRNA and protein expression in the murine KitK641E GIST model and in tissue microarrays of human GIST. Ntsr1 mRNA upregulation in KitK641E animals was confirmed by quantitative PCR. Ntsr1 immunoreactivity was not detected in the Kit positive ICC of WT mice, but was present in the Kit positive hyperplasia of KitK641E mice. In the normal human gut, NTSR1 immunoreactivity was detected in myenteric neurons but not in KIT positive ICC. Two independent tissue microarrays, including a total of 97 GIST, revealed NTSR1 immunoreactivity in all specimens, including the KIT negative GIST with PDGFRA mutation. NTSR1 immunoreactivity exhibited nuclear, cytoplasmic or mixed patterns, which might relate to variable levels of NTSR1 activation. As studies using radio-labeled NTSR1 ligand analogues for whole body tumor imaging and for targeted therapeutic interventions have already been reported, this study opens new perspectives for similar approaches in GIST

Recalling pain experienced during a colonoscopy: Pain expectation and variability

Objectives. This study investigated the relationship between participants\u2019 expected levels of pain intensity before a colonoscopy, pain intensity experienced while they were undergoing this medical procedure (real-time pain), and their retrospective evaluation of this experience. Design. Correlational design. Regression analyses were performed and mediational models were tested. Methods. Ninety patients who were about to undergo a colonoscopy were asked to report the pain intensity on a scale ranging from 0 (no pain) to 10 (extreme pain). They reported the expected intensity of pain before the examination, their real-time intensity of pain every 60 s during the colonoscopy, and their global retrospective evaluation of the pain experienced when the procedure was over. Results. Results confirmed that, regardless of participants\u2019 gender, the variability of the real-time pain distribution was a significant predictor of the accuracy of recall (i.e. the discrepancy between recalled pain and mean real-time pain). Moreover, participants\u2019 pain expectations preceding the examination were a significant predictor of the accuracy of recall. It was further demonstrated that the effect of patients\u2019 expectations on the discrepancy was mediated by the real-time pain variability. Conclusions. The results of the present study provide useful indications about what the target of interventions aimed at reducing the bias in pain recall should be