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Maple syrup urine disease (MSUD) is a rare recessively inherited metabolic disorder causing accumulation of branched chain amino acids leading to neonatal death, if untreated. Treatment for MSUD represents an unmet need because the current treatment with life-long low-protein diet is challenging to maintain, and despite treatment the risk of acute decompensations and neuropsychiatric symptoms remains. Here, based on significant liver contribution to the catabolism of the branched chain amino acid leucine, we develop a liver-directed adeno-associated virus (AAV8) gene therapy for MSUD. We establish and characterize the Bckdha ( branched chain keto acid dehydrogenase a ) −/− mouse that exhibits a lethal neonatal phenotype mimicking human MSUD. Animals were treated at P0 with intravenous human BCKDHA AAV8 vectors under the control of either a ubiquitous or a liver-specific promoter. BCKDHA gene transfer rescued the lethal phenotype. While the use of a ubiquitous promoter fully and sustainably rescued the disease (long-term survival, normal phenotype and correction of biochemical abnormalities), liver-specific expression of BCKDHA led to partial, though sustained rescue. Here we show efficacy of gene therapy for MSUD demonstrating its potential for clinical translation. Maple syrup urine disease (MSUD) is a rare inborn error of metabolism, which is currently treated with life-long low-protein diet that can be challenging to maintain. Here the authors develop an AAV8-directed gene therapy providing sustainable disease rescue in a mouse model of MSUD.

Seryl‐tRNA synthetase 1 (SARS1) deficiency is a rare autosomal recessive disorder presenting with neurodevelopmental delay, deafness, cardiomyopathy, and fatal metabolic decompensation triggered by febrile episodes. While amino acid chronic supplementation is established, no guidelines exist for acute management. We report the case of a 9‐year‐old male of Turkish origin with genetically confirmed SARS1 deficiency, admitted with fever, vomiting, hypotonia, and seizures. The clinical course rapidly progressed to metabolic decompensation and severe acute cardiac failure, characterised by a left ventricular ejection fraction of 20%, necessitating mechanical ventilation and vasopressor support. Notably, the patient's family history included the death of three siblings during similar febrile episodes. During hospitalisation, the patient's specific L‐serine supplementation dosage was progressively tripled concurrently with standard supportive care. Unlike the fatal outcomes observed in his siblings, untreated by L‐serine, the patient survived and recovered following this high‐dose regimen. Cardiac biomarkers normalised within 20 days, and follow‐up echocardiography at 1 month demonstrated complete resolution of myocardial oedema. However, a year later, the patient presented with another febrile crisis at 10 years old, and despite an emergency protocol, the patient developed severe biventricular dysfunction progressing to fatal cardiogenic shock. This constitutes the first documented survival of a SARS1‐related metabolic crisis managed with high‐dose L‐serine. The findings strongly suggest that early, aggressive escalation of L‐serine dosage can be a viable therapeutic strategy for acute decompensation in SARS1 deficiency. Highlights This case reports the first documented survival of acute metabolic decompensation in SARS1 deficiency, achieved by tripling the patient's baseline L‐serine supplementation alongside standard supportive care during a febrile crisis. The outcome, contrasted with the fatal course in three untreated siblings, supports early aggressive L‐serine escalation as a potentially life‐saving strategy in this ultra‐rare disorder.

The pandemic crisis has definitively exposed the limits of a development model that the crisis of the new millennium had already amply demonstrated. Urban commerce has been heavily affected by the polycrisis, requiring innovative solutions to overcome it. In Saint-Germain-en-Laye (SGL), the problem was addressed through a relaunch project aimed at transforming the city centre of SGL into an open-air urban market through the pedestrianisation of selected areas and encouraging multimodality and multifunctionality of spaces and services assisted by digital technologies. The goal was pursued by leveraging the sense of community of the inhabitants and the ability to interpret their needs by a team made up of planners and designers from the municipal administration of Saint Germain-en-Laye and researchers in several different disciplines from the Politecnico di Milano. Overall, the experience was configured as a co-design activity aimed at experimenting with new ways of urban resilience for citizens and business keepers particularly affected by the effects of the pandemic.

The researches of Adger (2000), Martini (2015) and Malcevschi et al. (2017) suggest that there is an indissoluble relationship between society, territory and economy, factors which have reciprocal influence on each other in the creation of a specific ecosystem. The connection between these three elements feeds the built environment processes, predisposing its life cycle to various types of resilience. By analysing certain case studies, this paper aims to illustrate various forms of social resilience comforted by the anticipatory approach. The solutions proposed are presented together with details of the process models adopted and subsequently linked to different project and management methodologies which can be connected to the specifics of the technological project.

This article provides insights on the urban regeneration project conduced in the densely populated centre of the “Costanzo Ciano” neighbourhood of Piacenza. Financed by MIBAC - Ministry of Heritage and Culture through the Creative Living Lab programme, the project is configured as a participatory urban regeneration action (Placemaking) aimed at testing various possible solutions for a more structured future renewal intervention. The organisational formula adopted distinguishes through the active involvement of the inhabitants at both the design and realisation stages. The output consists in the product to which the inhabitants have contributed but also, and most importantly, in the social relationships which have been formed, through which, the functional plan for the future renewal intervention has been laid out. The experience coherently follows the URBACT method principles while its cultural and practical implications refer to both the “dilemmas” theme1 posed by the current European debate regarding the strategic development of public spaces and the Placemaking tool in the Living Labs 2.0 formula2, for an innovative governance straddling theory and practice.

This paper refers to the theme of urban regeneration in the long term perspective, studying the particular intersection area between the future studies and the processes defining the contemporary design culture. The goal is to propose a first delimitation of the core of a research field that could be called ‘project anticipation’ and possible competitive areas of interest for technological and environmental design. This investigation is motivated by the belief that the actual profound transformations impose a fast and strong cultural maturation of the technologist who has to advance from the role of technical director to the one of main actor of change. The resumption of long-term project and the ability to create perspective visions leading institutions and social and economic players in the present complexity result as indispensable requirements which determine the integration of the new dimension of project on the temporary scale of ideas. 

This contribution contains an analysis of the relationship between theory and practice in architecture, started from the particular similarity between scientific and design research and intended to nurture the debate around the possible evolution of the disciplinary tools of Architectural Technology. The contents are organized as follows: In the first section, there are investigated the affinities that supported the constitution of the methodological and instrumental apparatus of the technological culture of design. The second part is introducing the relationship between technological culture of design and post-normal sciences as a possible answer to the particular conditions of complexity and uncertainty of the moment. The third section is emphasizing the analogy between the instrumentations of several research areas that operate between environmental sustainability, futures studies and technological and environmental design as a starting point for further operational insights.

Technology, mobility and the large availability of data have dramatically changed values, expectations, approaches and jobs as well as the ways of understanding, interacting, living and working of individuals and communities. Therefore a more comprehensive perspective and new ways of thinking, designing, planning and managing cities are urgently needed. Confronted with increased exigencies in the conditions of reduced resources and ever growing levels of complexity and instability, public administrations are desperately calling for help. Based on the innovations developed, tested and promoted in the framework of Civitas PROSPERITY European project (focused on enhancing the adoption and efficiency of Sustainable Urban Mobility Plans), the present contribution is extrapolating this experience offering insights on public capacity building and on the sustainable preparation and implementation of various urban policies and measures and especially of the ones regarding energy efficiency. The latter are being regarded from a comprehensive, integrated and inclusive perspective, being considered essential for the wealth of a city and of its inhabitants.

Today, the environmental sustainability and development model are linked to culture, urban regeneration and new economy. Conceptualized in the 90s, cultural industry has flourished with the affirmation of the creative economy and new systemic economic theories and is now advancing towards models of creative cities and regions representing the spatial expression of the post-industrial economy. The territorial dimension has a fundamental role in the development of creative environments, while the space of the creative class represents the new urban work-environment. The qualitative analysis of those places in terms of requests and performance distinguishes it as a motivating field for the application of the technological project.

The researches of Adger (2000), Martini (2015) and Malcevschi et al. (2017) suggest that there is an indissoluble relationship between society, territory and economy, factors which have reciprocal influence on each other in the creation of a specific ecosystem. The connection between these three elements feeds the built environment processes, predisposing its life cycle to various types of resilience. By analysing certain case studies, this paper aims to illustrate various forms of social resilience comforted by the anticipatory approach. The solutions proposed are presented together with details of the process models adopted and subsequently linked to different project and management methodologies which can be connected to the specifics of the technological project.