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Veno-venous Extracorporeal Membrane Oxygenation (ECMO) is used in the most severe cases of respiratory failure and further exacerbates the patients’ inflammatory status. Antithrombin is supplemented during ECMO for its anticoagulant effects, but it also deploys anti-inflammatory properties. In this pre-specified ancillary study of the GATRA trial [NCT03208270] we aimed to evaluate the relationship between antithrombin and inflammation during ECMO. Forty-six patients were included in the study, 23 were randomized to receive antithrombin to maintain a level of 80–120% (study group) and 23 were randomized not to be supplemented (control group). Anticoagulation was provided in both groups with heparin infusion. Six cytokines were measured at 5 timepoints from prior to ECMO start to 7 days after ECMO removal. Cytokines decreased during the study but overall were not very different in the two groups. Testing the interaction between the study group and timepoints suggests that the administration of antithrombin led to a more rapid decrease over time of IL-6, IL-1β, TNF-⍺ and Pro-ADM. Plasma levels of antithrombin (either endogenous or exogenous) were negatively associated with all cytokines. Inflammation decreases during ECMO but a causal effect of antithrombin administration on the reduction of inflammation (and its clinical relevance) must be confirmed by appropriately powered studies.

La divisione internazionale dei comparti produttivi, produce differenti collocazioni all'interno della geografia della competizione globale. Descrizione dei casi studio.

Il contributo riporta la sintesi di un'attività di ricerca triennale svolta nell'ambito di un progetto finanziato dal Ministero dello Sviluppo Economico. L'obiettivo del lavoro è verificare l'influenza di configurazioni topologiche delle imprese, in forma clusterizzata o indipendente, e tipologiche in termini di diverso settore industriale di loro afferenza, sui determinanti di scelta localizzativa in ambito urbano. L'analisi empirica ha riguardato l'area urbana di Napoli e il campione di imprese analizzate è stato selezionato in ottica della strategia regionale di sviluppo aziendale RIS3 (Research Innovation Smart Specialization Strategy) della Regione Campania per la piena conformità tra le linee di intervento ministeriali e quelle regionali.

Small and Medium Enterprises (SMEs) in urban areas are increasingly relevant, with a consistent impact on various territories. This research explores the re-territorialization processes, contextualized by the post-Fordism era, in urban areas. The objective of this work is to verify a hypothesis assumed at the base of the research relating to the presence of a uniformity of orientation regarding the settlement determinants of companies that are co-located in specific areas of the cities. This hypothesis is tested in relation to various industrial sectors. The availability of these survey elements constitutes a useful driver of awareness to be then translated into specific actions in urban planning in terms of policies, services and infrastructures to be dedicated to these urban spaces characterized by clusters of firms. From a methodological point of view, the followed approach is based on two aspects relating both to a cartographic comparison and both to a statistical comparison between the answers provided by the service companies of different sectors of some European cities selected for the sample survey.

EnglishA geographical analysis of the territorial impact of the University by identifying spatial clusters. The case of the Naples area - Globalization and the perennial hyper-connection due to the diffusion of communications technologies more and more apparently capable of annihilating geographical proximity, has aimed the recent scientific debate on the topic of network externalities, especially when these concern the relation relative to activities of research between universities and businesses located in the territory of reference. It makes sense, therefore, to critically reflect about the significance of spatial cluster configuration of the subjects who entertain such relationships, investigating their nature and intensity. This contribution, through the synthesis of a research activity developed as part of a multi-year project financed by the Italian Ministry of Economic Development, proposes an inductive approach starting from a concrete case study that has been analyzed. Even with the awareness of the conceptual complexity related to the enormous variety of configurations that the system of university-business and intra-companies relations and the related modeling assume, the proposed inductive methodological approach, based on the determination of thematic clusters and the subsequent analysis of nature of the typology of the exchanged relationships, it is functional to argue a critical answer to the question posed. italianoLa globalizzazione e l'iper-connessione perenne ad opera della diffusione di tecnologie per le comunicazioni, apparentemente sempre piu in grado di annichilire la prossimita geografica, hanno riacceso il recente dibattito scientifico sul tema delle esternalita di rete, soprattutto quando queste riguardano il nesso relativo ad attivita di ricerca tra universita ed imprese localizzate nel territorio di afferenza. Ha senso, pertanto, interrogarsi circa la valenza di configurazione di cluster spaziali dei soggetti che intrattengono tali relazioni, investigandone la loro natura e intensita. Tale contributo, attraverso la sintesi di una attivita di ricerca sviluppata nell'ambito di un progetto pluriennale finanziato dal Ministero dello Sviluppo Economico italiano, propone un approccio induttivo a partire da un caso studio concreto che e stato oggetto di analisi. L'approccio metodologico induttivo proposto, basato sulla determinazione di cluster tematici e sulla successiva analisi della natura e della tipologia delle relazioni scambiate, pur nella consapevolezza della complessita concettuale relativa alla enorme varieta di configurazioni che il sistema di relazioni universita-impresa ed intra-imprese e le relative modellazioni assumono, si rivela funzionale ad argomentare una risposta critica all'interrogativo posto.

The clinical outcome of the disease provoked by the SARS-CoV-2 infection, COVID-19, is largely due to the development of interstitial pneumonia accompanied by an Acute Respiratory Distress Syndrome (ARDS), often requiring ventilatory support therapy in Intensive Care Units (ICUs). Current epidemiologic evidence is demonstrating that the COVID-19 prognosis is significantly influenced by its acute complications. Among these, delirium figures as one of the most frequent and severe, especially in the emergency setting, where it shows a significantly negative prognostic impact. In this regard, the aim of our study is to identify clinical severity factors of delirium complicating COVID-19 related-ARDS. We performed a comparative and correlation analysis using demographics, comorbidities, multisystemic and delirium severity scores and anti-delirium therapy in two cohorts of ARDS patients with delirium, respectively, due to COVID-19 (n = 40) or other medical conditions (n = 39). Our results indicate that delirium in COVID-19-related ARDS is more severe since its onset despite a relatively less severe systemic condition at the point of ICU admission and required higher dosages of antipsychotic and non-benzodiazepinic sedative therapy respect to non-COVID patients. Finally, the correlation analysis showed a direct association between the male gender and maximum dosage of anti-delirium medications needed within the COVID-19 group, which was taken as a surrogate of delirium severity. Overall, our results seem to indicate that pathogenetic factors specifically associated to severe COVID-19 are responsible for the high severity of delirium, paving the way for future research focused on the mechanisms of the cognitive alterations associated with COVID-19.

OBJECTIVES: Extracorporeal carbon dioxide removal is used to treat patients suffering from acute respiratory failure. However, the procedure is hampered by the high blood flow required to achieve a significant CO2clearance. We aimed to develop an ultralow blood flow device to effectively remove CO2combined with continuous renal replacement therapy (CRRT). DESIGN: Preclinical, proof-of-concept study. SETTING: An extracorporeal circuit where 200 mL/min of blood flowed through a hemofilter connected to a closed-loop dialysate circuit. An ion-exchange resin acidified the dialysate upstream, a membrane lung to increase Pco2and promote CO2removal. PATIENTS: Six, 38.7 ± 2.0-kg female pigs. INTERVENTIONS: Different levels of acidification were tested (from 0 to 5 mEq/min). Two l/hr of postdilution CRRT were performed continuously. The respiratory rate was modified at each step to maintain arterial Pco2at 50 mm Hg. MEASUREMENTS AND MAIN RESULTS: Increasing acidification enhanced CO2removal efficiency of the membrane lung from 30 ± 5 (0 mEq/min) up to 145 ± 8 mL/min (5 mEq/min), with a 483% increase, representing the 73% ± 7% of the total body CO2production. Minute ventilation decreased accordingly from 6.5 ± 0.7 to 1.7 ± 0.5 L/min. No major side effects occurred, except for transient tachycardia episodes. As expected from the alveolar gas equation, the natural lung Pao2dropped at increasing acidification steps, given the high dissociation between the oxygenation and CO2removal capability of the device, thus Pao2decreased. CONCLUSIONS: This new extracorporeal ion-exchange resin-based multiple-organ support device proved extremely high efficiency in CO2removal and continuous renal support in a preclinical setting. Further studies are required before clinical implementation.

This paper examines the transboundary water resources conflict resolution mechanisms. Although different research perspectives, including social planner, water market, game theory, static and dynamic systems engineering model, have already provided conflict resolution mechanisms that could be used to analyze transboundary water conflicts, here an ecosystemic approach based on an analytical model, is proposed. For this aim the case of GERD "Grand Ethiopian Renaissance Dam" on Nile Azzurro, is analyzed. The scenario of the GERD dam, besides being current and interesting in the water dispute between Egypt, Sudan and Ethiopia, is suitable for the application of the proposed analytical model. This model could permit researchers and practitioners to develop more comprehensive mechanisms, complementary to political strategies, with stronger analytical capacity to analyze the different elements of the process of transboundary water dispute resolution.

Urban dynamics in recent years show a tendency that cannot be ignored in terms of the impacts that they induce, with regard to many companies, especially big companies, that are settled in the downtown districts of the main cities, where economic spaces are blended with urban spaces. This study, therefore, aims to investigate the sustainability of cities by using the specific perspective of their relationship with the companies’ urban settlements. Some questions in the present work are discussed: What advantages derive from the firms’ settlements in downtown areas? What is the impact on urban geographies? What role does urban policy play in this process? How do cities perceive this large business settlement? To answer to these questions, a model of dynamic equilibrium, referred to as the public–private relationship, is provided. The analysis starts from the context of the city as a commercial space, then identifies the determinants of the establishment of businesses in the city centers and the mediating function of politics in this urban morphogenesis. Case studies from the USA on large companies returning to urban centers complete the analysis.

Background In ICU patients, digestive tract colonization by multidrug-resistant (MDR) Gram-negative (G−) bacteria is a significant risk factor for the development of infections. In patients undergoing extracorporeal membrane oxygenation (ECMO), colonization by MDR bacteria and risk of subsequent nosocomial infections (NIs) have not been studied yet. The aim of this study is to evaluate the incidence, etiology, risk factors, impact on outcome of gastrointestinal colonization by MDR G− bacteria, and risk of subsequent infections in patients undergoing ECMO. Methods This is a retrospective analysis of prospectively collected data: 105 consecutive patients, treated with ECMO, were admitted to the ICU of an Italian tertiary referral center (San Gerardo Hospital, Monza, Italy) from January 2010 to November 2015. Rectal swabs for MDR G− bacteria were cultured at admission and twice a week. Only colonization and NIs by MDR G− bacteria were analyzed. Results Ninety-one included patients [48.5 (37–56) years old, 63% male, simplified acute physiology score II 37 (32–47)] underwent peripheral ECMO (87% veno-venous) for medical indications (79% ARDS). Nineteen (21%) patients were colonized by MDR G− bacteria. Male gender (OR 4.03, p = 0.029) and duration of mechanical ventilation (MV) before ECMO > 3 days (OR 3.57, p = 0.014) were associated with increased risk of colonization. Colonized patients had increased odds of infections by the colonizing germs (84% vs. 29%, p p = 0.002), MV (50 vs. 22 days, p p p = 0.480, OR 0.68). Infected patients had almost halved ICU survival (46% vs. 78%, p Conclusions In patients undergoing ECMO for respiratory and/or circulatory failure, colonization by MDR G− bacteria is frequent and associated with more the tenfold odds for subsequent infection. Those infections are associated with an increased risk of death.

A dichotomy often frequent in the context of geographic studies concerns the dualism between propagation and induction models-based phenomena, inherent in variables and factors characterizing contiguous areas, and research relating to homogeneity between geographically not closed areas. In the wake of the latter research, this contribution proposes a model that exploits the potential of graph theory for the evaluation of common dynamics relating to non-contiguous areas. The assumption underlying the model envisages configuring the reality being studied in terms of a network whose nodes and branches are respectively representative of entities distant from each other and of their related affinities. The proposed approach focuses on some Italian industrial districts. The value of the proposed approach is twofold, on the one hand regarding the specific industrial district topic with both scientific and practical implications, and on the other hand it aims to provide a method that can be replicated in similar scenarios in which it is interesting to evaluate the similarity between neighboring areas analytically.

In this paper a sensor data fusion approach for characteristics field monitoring, based on time variance control model, is proposed. Distributed sensing and remote processing are the basic features of the employed architecture. In fact, in order to obtain meaningful information about the temporal and spatial variations, which characterize the field levels of some characteristics (electromagnetic, air pollution, seismic, etc), a distributed network of wireless and mobile smart-sensors has been designed.Starting from the partitioned configuration of a monitored geographic areas, this model allows to take into account the different levels of degradation over time in the sensors' performances associated with the different geographic partitions, progressively increasing the severity of the control. To this end, through the introduction of a reliability curve, a revised traditional control chart for variables is proposed.The proposed approach, further constituting an element of the scientific debate, aims to be a useful operational tool for professionals and managers employed in the environment control.

For several years, the themes concerning agglomeration economies have been approached from different perspectives in the scientific debate, as capable of triggering various positive features. The present research starts precisely where many others arrive, that is, given the value of these externalities, analyzing the spatial distribution of the geographical concentration of economic activities and the related influencing factors. To this end, in this contribution an explanatory investigation is carried out into the spatial dynamics deriving from main productive sectors’ concentration in some Italian regions. The proposed methodological approach is based respectively on the LISA spatial autocorrelation models and on the analysis of non-neighboring clusters to understand if the geographical area of reference and / or the particular production sector are influencing variables. The empirical investigation confirms the presence of a parametric interaction between factors related in some cases on the geographical context and in others on the productive sector.

This paper asks what is the relationship between critical raw materials and cities within the European Union (EU)? To answer this question, this study seeks to categorise research findings on critical raw materials through a literature review. For this purpose, publications about critical raw materials have been systematically searched using a multidisciplinary scientific bibliographic database. Several screening criteria were applied to ensure the utmost accuracy and specificity in the development of research. During the review, the papers and the other publications found were systematised by dividing them into three thematic sections according to the focus adopted: critical raw materials as pollutants; their recycling; and the new technologies that can be applied to them. The results of the review show that the development of cities and their regeneration will increasingly depend on critical raw materials. Moreover, these findings suggest that soon the professionals who deal with urban regeneration and renewal will have to manage more and more issues related to critical raw materials. Furthermore, a correct understanding of the relationship between critical raw materials and cities is essential to avoid manipulation by populist parties which could use these strategic materials to support their autarchic rhetoric.

Typical of the 1990s, the global cities phenomenon preceded the past decade’s massive spread of smart cities. Yet the question of how the two phenomena currently coincide remains to be considered, ...

A fundamental objective for the effectiveness and, above all, for the efficiency of the dynamics of environmental sustainability is related to the correct directing of project actions towards those areas that need them most. This contribution intends to verify whether the spatial distribution of eco-innovation projects in some regions of Southern Italy affects areas characterized by greater environmental fragility. The proposed approach highlights a centrality of the spatial perspective, thus underlining how important and necessary it is for political actors to evaluate the goodness of projects not in absolute terms but in relation to their relationship with the territory in which they are implemented. To this end, the methodology used envisages two actions, a cartographic comparison between the distribution of environmental projects and that of environmental fragility and an analytical evaluation of the spatial autocorrelation between contiguous areas to detect any geographical determinisms. The results show a “positive” independence regarding the presence of eco-innovation even in the absence of environmental fragility but not vice versa.

To approach, in a scientific form, the issue of the analysis of the innovative character of the city of Naples, is a delicate and risky operation: positive and negative consolidated city representation paradigms represent a cumbersome burden which physiologically should be taken in charge. Any approach to the "Naples" issue, from the landscape, historical, artistic, cultural, economic, social, up to sports, has a boundless and ever growing evolution upon previous literature. In this article, there is neither presumption nor the aim of wanting one; in fact it provides an overview of the many different features of the Neapolitan territory that are as a result of an algorithm starting from assumptions, determined by the statement of the theorem that Naples is an innovative city. The aim, in a particularly happy and creative time for Naples, (Apple and Deloit have settled in the east area of Naples, while Cisco might invest in the area as well; Dolce & Gabbana recently organized a global event), is to try to check the validity of the "Florida's theorem" for this city, leaving, however, the reader the chance, the opportunity, and perhaps the pleasure, to judge the true and complete paradigm that governs the "Vesuvius Valley" and so answer this question: Are the famous folk icons of the city of Naples, such as Vesuvius, pizza and coffee, urban factors that help to create and to facilitate the urban creativity and innovation, or hinder them, because they obscure the part of science and scientific culture of the city? This aim will be reached, less as a scientific theorem and more as a proposal supported by objective elements to be "delivered" to the reader, through the following statement complex: I) it is true that in the Vesuvius valley people live in a creative climate; II) the creative climate of the Vesuvius valley is not generated "by necessity" caused by the absence of industries because Naples, in the past, was a Fordist city; III) Vesuvius valley is a post-Fordist urban area where a major effort is being made to enhance the knowledge economy and where Florida's third T, or Technology, is very present within Universities, research centers and the most technological companies in the world (Apple's settlement is an example).

In the last few decades, the tourism sector in Europe has been facing growing demands from travellers who want better access in hotels, at holiday destinations and tourist attractions. The number of European travellers in the 55+ age group is increasing and, together with disabled people and their families, these customers are looking for travel options where basic accessibility features are standard. The so-called accessible tourism for all is not about providing separate services for separate targets or niche tourist markets. It aims at full integration or rather the inclusion of people with special needs (age, size, disability) in the tourism sector. Its long-term goal is the creation of a tourist environment in which all tourists can participate actively. Viewed from the perspective of accessible tourism for all, tourism policy in the European Union can be said to unite accessibility targets that are part of the otherwise trade-related aspects of tourism policy and a disability policy that, based on the United Nations’ Standard Rules, support goals and specific measures at various levels that are designed to enhance accessibility in connection with tourism policy. Within this framework, the main purpose of this research is to investigate strategies and actions to which the European Commission is committed to increase accessibility in tourism. Using a qualitative methodology, the paper explores objectives and activities of some initiatives that are helping to make travel and tourism accessible for everyone. Therefore, it offers an overview of some projects and good practices taking place in European countries.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region.MethodsThis survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2–positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher’s exact tests for dichotomous answers and χ2 test for trends relative to the questions with 3 or more options.ResultsThis is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2–positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients’ planned treatment approach). The results from responders in Campania did not differ significantly from the national ones.ConclusionOur study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.

The scientific debate on Special Economic Zones (SEZ) shows many contributions, however the present work intends to offer an original perspective to this theme based on a comparison, through a systemic approach, between the sociourban variables, that make up the symbiotic relationships between SEZ, and urban society. A focus on the SEZ settled in the east of Naples, Italy, is also proposed, which well allows to highlight the investigated socio-urban aspects.

Il contributo si propone di indagare sul ruolo che le grandi aree urbane meridionali ricoprono all’interno dello spazio europeo, cercando di comprendere le dinamiche demografiche ed economiche in atto, e guardando con particolare attenzione al ridisegno delle gerarchie urbane e al ruolo e alle funzioni che le differenti tipologie di città rivestono nel network meridionale e nazionale, nonchè nello scenario europeo. L’analisi dei trend della popolazione residente mostra come l’armatura urbana del Paese riveli, anche nelle fasi di più intensi mutamenti economico-sociali, un forte carattere di resilienza nel dato macroregionale, che si traduce in una struttura tendenzialmente policentrica nelle regioni Centro-settentrionali, e in una maggiore presenza di città primaziali nelle regioni del Mezzogiorno. Alla sostanziale stabilità della tendenza macroregionale si affianca un quadro fortemente articolato alle scale inferiori. In particolare, si rileva un processo di spopolamento particolarmente rapido nei comuni delle aree interne con meno di 10.000 abitanti. Meno accentuata si presenta invece la dinamica dei comuni medi, mentre per i centri maggiori di 50.000 abitanti, dopo il picco della contrazione, particolarmente evidente negli anni 2009-2012, si registra un recupero demografico seguito da un successivo calo che riporta la situazione ai livelli precedenti. Obiettivo del lavoro è, dunque, in primis fornire un quadro di insieme che consenta di comprendere la situazione e l’evoluzione della rete urbana del Mezzogiorno e successivamente valutare se, a fronte delle perdite demografiche registrate dalle aree metropolitane meridionali, queste ultime possano ancora costituire dei poli di riferimento per il territorio. A tal fine verrà anche dedicato un focus al ruolo delle città medie in crescita, per verificare una eventuale trasferibilità di strategie virtuose di crescita e sviluppo.

The relationship between university and city over time has been subject to alternating phases, often also very controversial. In recent years, the theme relating to the push of the academic reality towards the territory has enriched the scientific debate making it now mature on this aspect. This paper explores the particular declination of this theme in the case of university decentralization in the suburban area, focusing critical analysis on local impacts and dynamics in relation to the glocal characteristics of the universities. The evaluation of the territorial impacts is developed in a Lefebvrerian perspective, epistemologically able to hold the city as an “urban society”, therefore, rich in social contradictions that the university must internalize, negotiating them in the best way. The characteristic of mediation, proposed by Lefebvre, is emphasized in the methodological proposed approach, firstly, on the basis of a review of the literature, identifying the most critical areas of the suburban areas that need regeneration and strengthening actions, and then placing the results in relation to the glocal characteristics of the university, defined according to national and international standards. The theoretical approach has also been declined and characterized in the specific case of the eastern suburban area of Naples, site of a recent university decentralization and of a consequent establishment of Academy of the main multinationals in the high-tech sector, which lends itself to being a perfect real laboratory for analyzing the discussed phenomena and paradigms., Bollettino della Società Geografica Italiana, Series 14 Vol 2 No 1 (2019)

Ex-situ machine perfusion (MP) techniques are increasingly used in clinical settings, especially on grafts derived from donors after cardiac death (DCD). However, comprehension of biological effects elicited during MP are largely unknown and a substantial number of animal studies are presently focused on this topic. The aim of the present study was to describe a model of DCD based on ex-situ perfusion of liver grafts derived from animals dedicated to food production. Procurement took place within a slaughterhouse facility. A clinically fashioned closed circuit normothermic MP (NMP) was built up. Autologous blood-enriched perfusion fluid was adopted. Perfusate and tissue samples were collected to asses NMP functionality. Grafts were classified as transplantable (LT-G) or not (n-LT) according to clinical criteria, while histopathological analysis was used to confirm graft viability. After cold storage, the liver grafts were connected to the NMP. During the rewarming phase, temperature and flows were progressively increased to reach target values. At the end of NMP, 4 grafts were classified as LT-G and 3 nLT-G. Histology confirmed absence of major damage in LT-G, while diffuse necrosis appeared in nLT-G. Interestingly, in nLT-G an early impairment of hepatocyte respiratory chain, leading to cell necrosis and graft non-viability, was documented for the first time. These parameters, together with indocyanine-green dye and citrate clearance could contribute to graft evaluation in clinical settings. In conclusion, this model provides a promising and reproducible method to replace dedicated experimental animals in DCD and MP research, in line with the 3Rs principles.

Background Normal levels of plasma antithrombin (AT) activity might decrease heparin requirements to achieve an adequate level of anticoagulation during treatment with extracorporeal membrane oxygenation (ECMO). Acquired AT deficiency during ECMO is common, but formal recommendations on target, timing, and rate of AT supplementation are lacking. Thus, we conceived a pilot trial to evaluate the feasibility and safety of prolonged AT supplementation in patients requiring veno-venous ECMO for respiratory failure. Methods Grifols Antithrombin Research Awards (GATRA) is a prospective, randomized, single blinded, multicenter, controlled two-arm trial. Patients undergoing veno-venous ECMO will be randomized to either receive AT supplementation to maintain a functional AT level between 80 and 120% (AT supplementation group) or not (control group) for the entire ECMO course. In both study groups, anticoagulation will be provided with unfractionated heparin following a standardized protocol. The primary endpoint will be the dose of heparin required to maintain the ratio of activated partial thromboplastin time between 1.5 and 2. Secondary endpoints will be the adequacy of anticoagulation and the incidence of hemorrhagic and thrombotic complications. Discussion GATRA is a pilot trial that will test the efficacy of a protocol of AT supplementation in decreasing the heparin dose and improving anticoagulation adequacy during ECMO. If positive, it might provide the basis for a future larger trial aimed at verifying the impact of AT supplementation on a composite outcome endpoint including hemorrhagic events, transfusion requirements, and mortality. Trial registration ClinicalTrials.gov, NCT03208270. Registered on 5 July 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3386-4) contains supplementary material, which is available to authorized users.

This is the era of the fourth industrial revolution. It is characterized by new, digital spaces in which individuals, especially digital natives, operate. It is in this new framework that digital spaces and physical urban spaces either mutually and constructively reinforce each other or destructively exclude each other. A conceptual reflection regarding Urban Constructive Interference and Urban Destructive Interference is thus explored in this work. These respective relationships between spaces consequentially affect urban transformations, particularly in consumption-based and entertainment-based places. These germinal relationships will become intrinsic in the fast-paced transformations of society and urban phenomena. This paper does not linger on comprehensive coverage of case studies or an exhaustive mapping of geographic relationships between digital and urban spaces. However, it does aim to provide a critical framework concerning the drive towards a future where urban spaces are governed by digital technology.

In Africa today there is a real startup explosion of remarkable value. There are several research and innovation hubs in the African continent, such as Silicon Cape, South Africa, and Silicon Savannah, Kenya. How are these initiatives autonomous and how can the more globally famous valley of innovation, Silicon Valley, inspire them? Above all, which paradigms are driving, and will continue to drive in the foreseeable future, the African continent in its development, moving from a continent with some areas still lacking electricity to another which is innovative and overcomes its barriers and internal obstacles? In response to these questions, this article aims to bring useful reflections and provide two parallel paths for innovation: one, a cultural roadmap, based on the development and the diffusion of knowledge and the other, a technological track, consequent to the first and based on technology. Statistical analysis complements the proposed reflections.

The “smart city” has risen to global prominence over the past two decades as an urban planning and development strategy. As a broad but contested toolkit of technological services and policy interventions aimed at improving the efficacy and efficiency of urban systems, the “smart city” is subject to several pressing critiques. This paper acknowledges these concerns, but recognizes the potential of “urban intelligence” to enhance the resiliency of metropolitan areas. As such, we focus on an under-researched dimension of smart city urbanism: its application in peripheral urban areas. The paper introduces a threefold typology of: (a) geographic (spatial); (b) hard (material); and (c) soft (social) urban peripherality. Second, it reviews the concept of urban resilience and considers how its central characteristics can inform the objectives and implementation of “smart city” infrastructures and planning. Six European smart city plans are assessed via a qualitative content analysis, to identify the target of smart city actions; the characteristics of urban resilience mobilized; and the spatial focus of planned interventions. The comparative analysis reveals a variegated set of smart-city approaches. Notably, “smart” actions aimed at enhancing social innovation are the most common type of intervention, while overall there remains a strong tendency for smart urbanism to focus on the urban core. We conclude by calling for a research agenda addressing smartness in, of, and for, peripheral urban spaces and communities.

The proportion of patients with metastatic colorectal cancer (mCRC) receiving second or further lines of treatment has not been widely studied. To shed light on this issue, we retrospectively analysed the treatments administered for metastatic disease, and investigated prognostic factors after a diagnosis of metastases, in a consecutive cohort of mCRC patients. Three hundred forty-six mCRC patients were enrolled: 173 were stage II or III (metachronous group), and 173 stage IV (synchronous group) at diagnosis. Survival was calculated between the date of metastatic disease and the date of death or last follow-up. Patients with synchronous lesions more frequently had multiple disease sites, peritoneal carcinomatosis and massive liver deposits, whereas significantly more patients with metachronous lesions developed lung metastases as the sole disease site. 97.4% patients received at least one, 62.4% two, 41.9% three and 23.7% four treatment lines. Patients with metachronous metastases more frequently underwent surgery of metastases in first-line treatment (48.5 versus 24.8%), and more of them were progression-free at the time of the analysis (44 versus 34.9%). At univariate analysis, age > 70 years, multiple disease sites and peritoneal carcinomatosis were associated with significantly decreased survival, whereas surgery of metastases and isolated lung metastases predicted better survival. At multivariate analysis, only peritoneal carcinomatosis and surgery of metastases independently affected survival. The percentage of patients who received an active treatment decreased going from first- to fourth-line treatment. However, the proportion of patients who received efficacious treatment in advanced line remained high. Surgery of metastases was the most important prognostic factors.

Sebbene molti studi considerino i processi di sviluppo urbano basati sulla conoscenza, le molteplici funzioni che le universita possono svolgere nelle aree suburbane sono raramente prese in considerazione all’interno del dibattito scientifico. Il presente contributo fornisce una visione sistemica delle caratteristiche delle universita che interessano le aree suburbane, e propone un caso di studio, relativo alla citta di Napoli, nel quale sono evidenziate le diverse esternalita del recente decentramento universitario nell’area suburbana orientale.

L’integrazione nell’area dell’Unione Europea ha significativamente contribuito, in un primo tempo a stabilizzare e, successivamente, a sostenere la crescita economica della Polonia che, a differenza di molti altri paesi del Continente è riuscita a riassorbire lo shock della crisi del 2008 in tempi molto brevi. Infatti, già con il 2010, pur subendo l’effetto della lenta crescita di tutta la compagine europea, il paese è riuscito a restituire vigore alla propria economia sino a riposizionarsi, stabilmente, su di un livello d’incremento del proprio PIL intorno a tassi del 4% annui. La ricerca che si presenta in questa sede intende, in primo luogo, dimostrare come l’adesione all’UE, attraverso investimenti mirati, gestiti a livello centralizzato in funzione di ben calibrati obiettivi di sviluppo, abbia consentito al paese di migliorare le condizioni di vita della propria popolazione e stabilire valide premesse per il suo inserimento in un contesto di internazionalizzazione dell’apparato produttivo e del modello dei consumi interni. Il contributo, inoltre, affronta la delicata questione della coesione territoriale dello sviluppo regionale evidenziando come, a fronte di aree intensamente attive nel processo di crescita economica, tra le quali la regione della Pomerania, sussistano tutt’ora sacche di stagnazione e realtà affatto inserite nel contesto di un moderno processo di innovazione e crescita. Il nucleo centrale della ricerca di cui si presentano i risultati, ruota intorno all’approfondimento dei meccanismi virtuosi di pianificazione regionale per evidenziare e isolare le prassi da cui sia possibile far discendere i risultati maggiormente positivi in termini di rimodulazione e vivacizzazione del tessuto produttivo. Infine, con l’intento di avanzare talune ipotesi circa la permeabilità e replicabilità delle politiche territoriali, vengono prospettate alcune considerazioni in ordine alla sussistenza dei vincoli che, in concreto, rischiano di comprometterne la pratica trasferibilità nelle regioni tuttora marginali. The integration in the European Union has contributed significantly, initially to stabilize and, subsequently, to support the economic growth of Poland, which, unlike many other countries of the Continent, has managed to absorb the shock of the crisis in the 2008 very quickly. In fact, already in 2010, despite suffering the slow growth of the entire European frame, the country has managed to restore vigor to its economy until it repositions, steadily, on a level of increase of its GDP around rates 4% per year. The proposed contribute primarily aims to demonstrate how access to the EU, through targeted investments, managed at centralized level according to well-calibrated development objectives, has enabled the country to improve the living conditions of the own population and establish valid premises for its insertion in a internationalization context both of the productive apparatus and both of the model of internal consumption. The contribute also addresses the delicate issue of territorial cohesion in regional development, highlighting how, despite of intensively active areas in the process of economic growth, such as the Pomeranian region, there are still ones of stagnation and reality neither included in the context of a modern process of innovation and growth. The core of the research revolves around the deepening of the virtuous mechanisms of regional planning to highlight and isolate the practices from which it is possible to bring down the most positive results in terms of remodeling and vivacization of the productive context. Finally, with the intention of making certain assumptions about the permeability and repeatability of territorial policies, some considerations are envisaged with regard to the existence of the constraints which, in practice, risk compromising the practical transferability in the still marginal regions.

The aim of this paper is to give an answer to the question “how to detect the regional dimension of innovation?”. So, in this paper, a method to be used as an operational tool that is able to grasp regional specificities in the innovation process, based on the optimization of measurement activity, is proposed. Evidence in the scientific literature shows that data and indicators are able to quantify the contribution of different regions, identify the different technological profiles of the regions and measure the technological performances of regional systems, the innovative performances of firms and the density and quality of systemic interactions between the main institutional actors, but these items are often not developed through an analytical model of measure control cost based on the optimization of certain influencing factors. The proposed approach is based on two main points: 1) Define the opportune methodology to detect the innovation level of a single firm. For this aim it has been considered the AICTT-RTA protocol. Each SME, is considered as innovative or as non-innovative according to the outcome of a Technology Audit (TA) conducted in compliance with the AICTT-RTA protocol. 2) Determine, starting only from some of the SMEs in a certain monitored area, if the entire area is innovative or not, through TA on a optimal sample size of SMEs analyzed. For this second point the approach uses a bayesian analysis of the Deming cost model. This approach considers a wide area, industrial or urban, in which SMEs are present and treats it as a lot of N items. Through the proposed approach, to characterize the regional innovation it’s sufficient to characterize just only some SMEs, however detecting the whole regional innovation profile. In this paper this aspect is valorized and set in the form of a useful operational tool for regional institutions, innovation managers, entrepreneurs and researchers. Simulation results complement the proposed theoretical model.

BackgroundAnalysis of K- and N-RAS mutations is mandatory before planning treatment of metastatic colorectal cancer, because only RAS wild-type (WT) patients can benefit from treatment with anti-EGFR monoclonal antibodies (cetuximab and panitumumab).Case reportHere we report the case of a 69-year-old male patient affected by metastatic sigmoid cancer. He underwent left hemicolectomy, and histology diagnosed a well-differentiated, pT4, node-positive adenocarcinoma; KRAS analysis performed with direct sequencing identified a mutation in exon 2 of the KRAS gene (GGT->GTT). After first-line chemotherapy with FOLFOX6 plus bevacizumab, the patient underwent surgical resection of residual liver metastases. Histology showed metastatic deposits from colic adenocarcinoma with extensive coagulative necrosis. Mutational analysis of the KRAS gene was also performed on liver metastases by pyrosequencing assay, and no mutation was identified. Due to the discordant results (GGT->GTT exon 2 KRAS mutation in the primary tumor, and KRAS-WT in the liver metastases), mutational analysis on liver metastasis was repeated using next-generation sequencing and enriching the sample in tumor cells by manual microdissection; the same type of mutation of the primary tumor (GGT->GTT exon 2 KRAS gene) was confirmed.ConclusionsAccurate tissue sampling and adequately sensitive assays are essential to correctly identify colorectal cancer patients who can be treated with an anti-EGFR monoclonal antibody.

Is it possible to control and optimize technology transfer process? Engineers and quality practitioners are often faced with the problem of determining the optimal choice of key factor in the tolerance process evaluation regarding the quality of the process to be monitored. To guarantee a prefixed quality level of the monitored process, lower specification limit (LSL) and upper specification limit (USL) for a certain quality characteristic have been determined. These limits, LSL and USL, could be defined as μ − δσ and μ + δσ, respectively, where δ > 0. Here, the key factor δ represents the number of standard deviations at which each specification limit is located from the process mean. This paper shows an innovative use of SPC tools in a different field aspect, one in which they are usually employed. Generally, these instruments are used for the control of the industrial process or service, but they could be used in an innovative way to control and to optimize a particular process: the technology transfer process. When determining the key factor level, it is important to consider a trade-off between costs incurred by the supplier, in terms of technology offer, and the user, in terms of technology request, of the process examined. This paper shows how these costs are quantified and integrated; it also shows how a particular mathematical tool, the Lambert W function, is incorporated into this choice optimization problem by deriving a closed-form solution. This proposed model and solution may be appealing to managers and technology transfer operators since the Lambert function is found in a number of standard optimization software. Experimental results are presented and related to a real data set of technology transfer actions developed by the Technology Transfer Office.

Rationale: Paraneoplastic limbic encephalitis (PLE) is one of the most common causes of neurologic paraneoplastic syndromes, with unclear pathogenesis. While several reports published in the last decades showed the occurrence of PLE in a variety of cancers, only a few cases have been associated with colon cancer. Patient concerns: In February 2017, a 54-year-old man with clinical history of radically resected colon cancer started first line chemotherapy with FOLFOXIRI plus bevacizumab, after radiological diagnosis of multiple liver and bone metastases. During the third cycle of treatment, the patient developed psychomotor agitation and hallucinations followed by severe consciousness level reduction and cognitive impairment. Diagnoses: Magnetic resonance imaging showed hyperintense signals in both hippocampal areas, insula and right cingulate gyrus on fluid attenuated inversion recovery, diffusion weighted imaging, and T2-weighted images, highly suggestive of limbic encephalitis. Other causes (brain metastases, toxicity of chemotherapeutic agents, and infections) were excluded. Interventions: Empirical immunosuppressive treatment (high-dose immunoglobulins and corticosteroids) was administered and chemotherapy was resumed. Outcomes: A slowly progressive improvement in neurological condition has been observed, even though radiological signs of limbic encephalitis are still evident. Lessons: The present case highlights the complex diagnostic process of PLE, and the lack of a standard treatment. Moreover, the absence of correlation between PLE and tumor progression or tumor burden, and the opportunity of treating underlying neoplasm is discussed.

With the growing competition in a globalized world, universities are seen as the key organizations and supporters in the national innovation system (Audretsch et al. 2006). Thus, national and regional policy makers try to set incentives for innovations and to increase the innovative potential of universities and to use it effectively. A large and diverse literature analyzes the importance of universities within the regional and national innovation system (Mowery and Sampat 2005; Cosh and Hughes 2010; Audretsch et al. 2011), often highlighting the necessity of separate and specialized organizational units to manage industry–university collaborations (Link et al. 2008; Fritsch and Lukas 2001). Within this process, TTO are seen as the institutionalized way to transport and canalize the ideas, inventions and innovations of academic researchers into the (regional) industry and society (van Ledebur 2008; Meoli et al. 2011; Gonzales-Pernia et al. 2011). Thus, given the importance attached to TTO within this process, policy makers and university management should be interested in the performance differences of TTO. During its activity, after a certain period, we can define as the “performance life”, continuing to try to transfer to the industry the same technologies leads to heavy financial loss to the TTO, because innovations and their commercialization, based on networking effects between the academic researchers and the industry, with TTO as the hub of the university–industry, determine market saturation. In this article, we deal with estimation of “performance life” for the invention disclosures by TTO and determination of replacement plan. This “performance life” has been modeled using a piecewise linear-quadratic TTFR function. A computational procedure is proposed for estimation of performance life. Hulsbeck et al., (2011) used the number of invention disclosures as a performance measure, to analyze how variance in performance can be explained by different organizational structures and variables of TTO. In this paper we refer to the same performance measure to be monitored. The approach of the present study declines the exposed issue to the specific case of marginal urban area. Results of an empirical analysis are proposed. It regards to a real case, based on the analysis of the impacts of the recent settlement of a research center, the center Cesma of the University of Naples Federico II, in marginal east area of the city of Naples, in which the local administration has decided to implement requalification actions. Finally, a technology transfer replacement plan for TTO is derived. This proposed model and solution may be appealing to geographers, managers and technology transfer agents since the graphs and tables proposed could be reproduced in a number of standard optimization software.

Education is the main activity for universities but the innovations resulting from their research become more and more a prominent and very lucrative business for them. University research and its transfer to industry has been a topic of interest in the management of technology literature over decades and several researchers focused the performances of university TTOs and many metrics have been proposed during last years . The primary role of a TTO is to manage and perform technology transfer activities (AUTM 2004), but how to control and monitoring the performance of university TTOs? In literature there are many studies regarding this theme, but many of these focused on the analysis of the driving forces of TTO performances that may help policy makers and university managers to improve technology transfer process (Hulsbeck et al., 2013), while in this paper, the approach to this theme regards the use of operative tools to control and monitoring the performance of university TTOs. TT managers oriented to use statistical tools, as a control chart, here proposed, to do this, face with an operative problem related the small samples of TT available data that can generate bias of the process only owned to this condition and not as a consequence of a bias really occurred. In this paper, to overcome this problem, opportune graphs and tables, can be used by TT managers, are proposed to determine a reasonable number of subgroups of available TT data, for constructing suitable control limits. Hulsbeck et al., (2013) used the number of invention disclosures as a performance measure, to analyze how variance in performance can be explained by different organizational structures and variables of TTO. In this paper we refer to the same performance measure to be monitored. This proposed model and solution may be appealing to managers and technology transfer agents since the graphs and tables proposed could be reproduced in a number of standard optimization software.

Background The standard treatment for patients with locally advanced rectal cancer (clinical tumor, node, metastases [TNM] stage II or III) is radiotherapy before surgery (with or without concomitant fluoropyrimidine-based chemotherapy) followed by surgery. The role of adjuvant chemotherapy in this setting of patients is controversial in terms of the overall benefit on survival, the subgroup of patients who might not need it, and the best regimen (combination regimens vs. fluoropyrimidine alone). Patients and Methods Based on the retrospective analysis of the clinical outcome of all patients with locally advanced rectal adenocarcinoma treated at our institute during the past 9 years, we comment on prognostic factors for local and distant metastases of patients who received neoadjuvant treatment followed by surgery, and the scientific evidence that can help to decide the adjuvant chemotherapy. Results We conclude that pathological TNM stage after neoadjuvant chemoradiation (ypTNM) stage after surgery significantly affects disease-free and overall survival. In particular, patients with pathologically positive lymph nodes (ypN+) after surgery have a high probability of developing distant metastases. Conclusion ypN+ patients are candidate for intensified adjuvant chemotherapy.

e20109Background: Patients (pts) with thymic epithelial tumour (TET) are more likely to have an autoimmune disease during their lives. The association of Good syndrome and hematological manifestati...

In this paper a telemedicine application in support of heart patients homecare is proposed. Diagnosis of cardiac arrhythmias typically requires heart monitoring for 24 or 48 consecutive hours, so it causes long waiting lists in Hospital. In this sight the authors have projected an user-friendly virtual assistant able to acquire and analyze patient ECG signals by soft computing procedures. The system is based on a PDA equipped with a DAQ card acquiring, to a fixed sampling frequency, the heart electrical impulses by means of an ECG sensor. Then an embedded algorithm allows to depict the graph of the electrocardiogram on the PDA display. By build-in models the ECG waveform is analyzed in order to diagnose possible arrhythmias occurrences or the happening of a heart attack. In fact, the developed computational intelligence application enables the system to perform a patterns recognition taking into account information on the measurement uncertainty. In this way, according to some patient parameters like age, sex and physical constitution, a set of warning lights on display provides information on the current heart status of the patient. Consequently the heart report can be sent by a GPRS modem to a confidential Web page containing patient personal data. The M2M application allows information to be made available to expert medical staff of hospital or clinic for a further remote analysis. In presence of a potential emergency, an on-line doctor can decide the typology of intervention for the patient assistance.

Is it possible to control and optimize technology transfer process? Engineers and quality practitioners are often faced with the problem of determining the optimal choice of key factor in the tolerance process evaluation regarding the quality of the process to be monitored. To guarantee a prefixed quality level of the monitored process, lower specification limit (LSL) and upper specification limit (USL) for a certain quality characteristic have been determined. These limits, LSL and USL, could be defined as æ - ds and æ + ds, respectively, where d > 0. Here, the key factor d represents the number of standard deviations at which each specification limit is located from the process mean. This paper shows an innovative use of SPC tools in a different field aspect, one in which they are usually employed. Generally, these instruments are used for the control of the industrial process or service, but they could be used in an innovative way to control and to optimize a particular process: the technology transfer process. When determining the key factor level, it is important to consider a trade-off between costs incurred by the supplier, in terms of technology offer, and the user, in terms of technology request, of the process examined. This paper shows how these costs are quantified and integrated; it also shows how a particular mathematical tool, the Lambert W function, is incorporated into this choice optimization problem by deriving a closed-form solution. This proposed model and solution may be appealing to managers and technology transfer operators since the Lambert function is found in a number of standard optimization software. Experimental results are presented and related to a real data set of technology transfer actions developed by the Technology Transfer Office.

This paper focuses on the spatial development problem of university-led innovation in peripheral urban areas. Highlighting issues of proximity, uneven geographic development, and multi-scalar urban governance as weaknesses of the regional innovation systems literature, we provide a novel synthesis of regional economics, innovation policy, and critical urban studies to assess the development roles of universities in concrete contexts. A comparative investigation of Naples and Newark, NJ captures the functional operation of regional innovation and urban development as a contested product of discourses, technologies (material and governance), and territorial arrangements. Our analysis demonstrates the significance of multi-scalar relationships in structuring innovation policy and practice in peripheral urban areas. The architecture of innovation is not simply rolled out into pre-determined spatial containers in places lacking established ‘institutional thickness’ or urban centrality. The spatial development of university-led innovation is a social product: material and governance infrastructures are essential components of the urban fabric and are essential to its co-constitution. Universities are shown to contribute differing resources dependent on their institutional strategic goals and the capacities and spatial imaginaries afforded to them by their situation in broader territorial governance regimes. We conclude by drawing comparative lessons and identifying directions for future research.

Le politiche per la sostenibilità urbana sono fondamentali per raggiungere l’undicesimo Obiettivo di Sviluppo Sostenibile. Lo scopo di questa ricerca è misurare l’impegno delle città nel salvaguardare il loro patrimonio naturale e nel rendere inclusivi e accessibili gli spazi verdi urbani pubblici. Rispetto agli indicatori delle Nazioni Unite e dell’ISTAT, qui ne sono proposti altri che tengono conto delle azioni locali di istituzioni e associazioni di cittadini per la gestione, lo sviluppo e la tutela del verde urbano. Inoltre, sono introdotte misure di dotazione del verde per classi di popolazione fragile. Gli indicatori sono calcolati per i capoluoghi di Regione italiani utilizzando i più recenti dati ISTAT sul Verde Urbano, al fine di delineare una mappa della sostenibilità verde urbana in Italia.