Effective metropolitan governance is not an outcome just from a law making process. The Italian case

The Delrio law has been ruling in Italy since the beginning of 2015, and it defines the boundaries of the ex Italian provinces, as metropolitan perimeters. Consequently, numerous problems have arisen from the resulting spatial configuration, both in terms of governance and metropolitan visioning, since only in very few cities the newly established metropolitan boundaries are coherent with urban systems’ dynamics and changes. The analysis of the Italian case helps to demonstrate that effective metropolitan governance does not stem only from a Government-driven and top down provision, and confirms that metropolitan development and governance require the development and strengthening of no-statutory and voluntary approaches, with a strong involvement of the business community. In order to illustrate and critically evaluate the recent Italian experience, this paper presents the results of a comparative analysis of a range of European polycentric metropolitan and industrial areas: Amsterdam (NL), Rotterdam-Den Haag (NL), Lille (FR), Barcelona (ES), Ruhrgebeit (DE). After a dramatic crisis caused by deindustrialisation and economic restructuring, they are all focusing on innovation, the establishment of new high-quality local services, and greater orientation to international competitiveness. These strategies do not stem directly from Government-driven regulation for local authorities, but are, to a large extent, dependent upon cooperative and nostatutory efforts. Moreover, the spatial scales of these initiatives are not always coincident with previous administrative boundaries. As a result, both in case of institutionalized metropolitan authorities as formal level of government, and in case of the absence of formal metropolitan institutions, this paper demonstrates that territorial cooperation is the essential basis for any metropolitan process, that often imply associations of municipalities and other local actors, sharing a common vision, and implementing strategic development projects

Analysis of KRAS, NRAS and BRAF mutational profile by combination of in-tube hybridization and universal tag-microarray in tumor tissue and plasma of colorectal cancer patients.

Microarray technology fails in detecting point mutations present in a small fraction of cells from heterogeneous tissue samples or in plasma in a background of wild-type cell-free circulating tumor DNA (ctDNA). The aim of this study is to overcome the lack of sensitivity and specificity of current microarray approaches introducing a rapid and sensitive microarray-based assay for the multiplex detection of minority mutations of oncogenes (KRAS, NRAS and BRAF) with relevant diagnostics implications in tissue biopsies and plasma samples in metastatic colorectal cancer patients. In our approach, either wild-type or mutated PCR fragments are hybridized in solution, in a temperature gradient, with a set of reporters with a 5' domain, complementary to the target sequences and a 3' domain complementary to a surface immobilized probe. Upon specific hybridization in solution, which occurs specifically thanks to the temperature gradients, wild-type and mutated samples are captured at specific location on the surface by hybridization of the 3' reporter domain with its complementary immobilized probe sequence. The most common mutations in KRAS, NRAS and BRAF genes were detected in less than 90 minutes in tissue biopsies and plasma samples of metastatic colorectal cancer patients. Moreover, the method was able to reveal mutant alleles representing less than 0,3% of total DNA. We demonstrated detection limits superior to those provided by many current technologies in the detection of RAS and BRAF gene superfamily mutations, a level of sensitivity compatible with the analysis of cell free circulating tumor DNA in liquid biopsy