Metropolitan Governance for Territorial Cohesion

This paper proposes and defines new metropolitan governance strategies for territorial cohesion between inland and urban areas. Different reflections are here presented to comprehend how is it possible to implement cities’ ability to understand and manage metropolitan dynamics. In Europe, urbanisation and land abandonment is a widespread phenomenon compared to many other parts of the world. According to research carried out by the European Union it is estimated that four out of five European citizens will be living in urban areas abandoning villages and rural areas. Many European metropolitan areas are character-rized by overpopulated centres, degraded suburbs and different abandoned or almost abandoned inland areas. These areas, if well connected among them and to the main metropolitan centre, can contribute to solving many urban challenges. There is the necessity to image metropolitan areas as a single entity to increase the cohesion of lands. The latent capital of inland areas can be considered as driving factor behind territorial cohesion and development. This paper analyses in deep the case of the Italian Metropolitan Cities proposing a new governance approach to increase the capacity of urban systems to adapt to natural and man-made changes, considering the hinterland as a strong point rather than a disadvantage. Strategic and Spatial Plans drive the growth of metropolitan areas in a competitive space-economy and support sustainable development policy by ensuring a balance between urban areas with strong competitiveness and inland area

Gastric cancer is the leading cause of death in Italian adult patients with common variable immunodeficiency

An increased prevalence of malignant lymphoma and of gastric cancer has been observed in large cohorts of patients with common variable immunodeficiency (CVID), the most frequently symptomatic primary immunodeficiency. Surveillance strategies for cancers in CVID should be defined based on epidemiological data. Risks and mortality for cancers among 455 Italian patients with CVID were compared to cancer incidence data from the Italian Cancer Registry database. CVID patients showed an increased cancer incidence for all sites combined (Obs = 133, SIR = 2.4; 95%CI = 1.7\u20133.5), due to an excess of non-Hodgkin lymphoma (Obs = 33, SIR = 14.3; 95%CI = 8.4\u201322.6) and of gastric cancer (Obs = 25; SIR = 6.4; 95%CI = 3.2\u201312.5). CVID patients with gastric cancer and lymphoma had a worse survival in comparison to cancer-free CVID (HR: 4.8, 95%CI: 4.2\u201344.4 and HR: 4.2, 95%CI: 2.8\u201344.4). Similar to what observed in other series, CVID-associated lymphomas were more likely to be of B cell origin and often occurred at extra-nodal sites. We collected the largest case-series of gastric cancers in CVID subjects. In contrast to other reports, gastric cancer was the leading cause of death in CVID. Standardized mortality ratio indicated a 10.1-fold excess mortality among CVID patients with gastric cancer. CVID developed gastric cancer 15 years earlier than the normative population, but they had a similar overall survival. Only CVID diagnosed at early stage gastric cancer survived >24 months. Stomach histology from upper endoscopy performed before cancer onset showed areas of atrophic gastritis, intestinal metaplasia or dysplasia. CVID patients might progress rapidly to an advanced cancer stage as shown by patients developing a III-IV stage gastric cancer within 1 year from an endoscopy without signs of dysplasia. Based on high rate of mortality due to gastric cancer in Italian CVID patients, we hereby suggest a strategy aimed at early diagnosis, based on regular upper endoscopy and on Helicobacter pylori infection treatment, recommending an implementation of national guidelines

A non-conserved amino acid variant regulates differential signalling between human and mouse CD28

CD28 superagonistic antibodies (CD28SAb) can preferentially activate and expand immunosuppressive regulatory T cells (Treg) in mice. However, pre-clinical trials assessing CD28SAbs for the therapy of autoimmune diseases reveal severe systemic inflammatory response syndrome in humans, thereby implying the existence of distinct signalling abilities between human and mouse CD28. Here, we show that a single amino acid variant within the C-terminal proline-rich motif of human and mouse CD28 (P212 in human vs. A210 in mouse) regulates CD28-induced NF-κB activation and pro-inflammatory cytokine gene expression. Moreover, this Y209APP212 sequence in humans is crucial for the association of CD28 with the Nck adaptor protein for actin cytoskeleton reorganisation events necessary for CD28 autonomous signalling. This study thus unveils different outcomes between human and mouse CD28 signalling to underscore the importance of species difference when transferring results from preclinical models to the bedside

A sharp quantitative Alexandrov inequality and applications to volume preserving geometric flows in 3D

We study the asymptotic behavior of the volume preserving mean curvature and the Mullins-Sekerka flat flow in three dimensional space. Motivated by this we establish a 3D sharp quantitative version of the Alexandrov inequality for $C^2$-regular sets with a perimeter bound

Participatory Mapping for Enhancing Flood Risk Resilient and Sustainable Urban Drainage: A Collaborative Approach for the Genoa Case Study

Abstract: Planning for resilient cities requires an evidence-based understanding of flood risk and the involvement of stakeholders and local actors. The paper addresses research developed within the URCA!—Urban Resilience to Climate Change: to activate the participatory mapping and decision support tool for enhancing sustainable urban drainage—project. A top-down/bottom-up participatory and flexible methodology for the conception of participatory mapping aimed at the planning and installation of sustainable urban drainage systems (SUDS) on the territory is then developed. The innovative methodology is applied and tested in the case study of the Sampierdarena district in Genoa, northern Italy. This research paper illustrates the development of a participatory map (Pmap) that can support the implementation of SUDS as mitigation/adaptation strategies, integrating technical assessment and containing community visions and expectations. Findings concerning the connections between proposed SUDS locations and their frequencies confirm the relevance of the commercial area and the main traffic lanes along, confirming that all zones characterized by intense vehicular and pedestrian flow are suitable for SUDS as a solution to contribute to urban flood resilience. The georeferenced and intergenerational Pmap may be integrated into a decision support system to be developed as a guidance tool for the public administration

Trogocytosis in innate immunity to cancer is an intimate relationship with unexpected outcomes

Trogocytosis is a cellular process whereby a cell acquires a membrane fragment from a donor cell in a contact-dependent manner allowing for the transfer of surface proteins with functional integrity. It is involved in various biological processes, including cell-cell communication, immune regulation, and response to pathogens and cancer cells, with poorly defined molecular mechanisms. With the exception of eosinophils, trogocytosis has been reported in most immune cells and plays diverse roles in the modulation of anti-tumor immune responses. Here, we report that eosinophils acquire membrane fragments from tumor cells early after contact through the CD11b/CD18 integrin complex. We discuss the impact of trogocytosis in innate immune cells on cancer progression in the context of the evidence that eosinophils can engage in trogocytosis with tumor cells. We also discuss shared and cell-specific mechanisms underlying this process based on in silico modeling and provide a hypothetical molecular model for the stabilization of the immunological synapse operating in granulocytes and possibly other innate immune cells that enables trogocytosis