A maritime decision support system to assess risk in the presence of environmental uncertainties: the REP10 experiment

The aim of this work is to report on an activity carried out during the 2010 Recognized Environmental Picture experiment, held in the Ligurian Sea during summer 2010. The activity was the first at-sea test of the recently developed decision support system (DSS) for operation planning, which had previously been tested in an artificial experiment. The DSS assesses the impact of both environmental conditions (meteorological and oceanographic) and non-environmental conditions (such as traffic density maps) on people and assets involved in the operation and helps in deciding a course of action that allows safer operation. More precisely, the environmental variables (such as wind speed, current speed and significant wave height) taken as input by the DSS are the ones forecasted by a super-ensemble model, which fuses the forecasts provided by multiple forecasting centres. The uncertainties associated with the DSS's inputs (generally due to disagreement between forecasts) are propagated through the DSS's output by using the unscented transform. In this way, the system is not only able to provide a traffic light map (run/not run the operation), but also to specify the confidence level associated with each action. This feature was tested on a particular type of operation with underwater gliders: the glider surfacing for data transmission. It is also shown how the availability of a glider path prediction tool provides surfacing options along the predicted path. The applicability to different operations is demonstrated by applying the same system to support diver operations

Extracellular vesicles circulating in young organisms promote healthy longevity

Parabiosis experiments in mice demonstrated that a young environment could partially rejuvenate multiple tissues of old organisms. However, the circulating mediators responsible of such effect have been elusive so far. Novel results suggest that extracellular vesicles isolated from plasma of young mice increase lifespan in old mice. Here we integrate these findings in a larger framework, advancing the hypothesis that circulating vesicles may mediate the beneficial effect of a young milieu on ageing

Cigarette smoke promotes inflammasome-independent activation of caspase-1 and -4 leading to gasdermin D cleavage in human macrophages

Mechanisms and consequences of gasdermin D (GSDMD) activation in cigarette smoke (CS)-associated inflammation and lung disease are unknown. GSDMD is a downstream effector of caspase-1, -8, and -4. Upon cleavage, GSDMD generates pores into cell membranes. Different degrees of GSDMD activation are associated with a range of physiological outputs ranging from cell hyperactivation to pyroptosis. We have previously reported that in human monocyte-derived macrophages CS extract (CSE) inhibits the NLRP3 inflammasome and shifts the response to lipopolysaccharide (LPS) towards the TLR4-TRIF axis leading to activation of caspase-8, which, in turn, activates caspase-1. In the present work, we investigated whether other ASC-dependent inflammasomes could be involved in caspase activation by CSE and whether caspase activation led to GSDMD cleavage and other downstream effects. Presented results demonstrate that CSE promoted ASC-independent activation of caspase-1 leading to GSDMD cleavage and increased cell permeability, in the absence of cell death. GSDMD cleavage was strongly enhanced upon stimulation with LPS+CSE, suggesting a synergistic effect between the two stimuli. Noteworthy, CSE promoted LPS internalization leading to caspase-4 activation, thus contributing to increased GSDMD cleavage. Caspase-dependent GSDMD cleavage was associated with mitochondrial superoxide generation. Increased cleaved GSDMD was found in lung macrophages of smokers compared to ex-smokers and non-smoking controls. Our findings revealed that ASC-independent activation of caspase-1, -4, and -8 and GSDMD cleavage upon exposure to CS may contribute to macrophage dysfunction and feed the chronic inflammation observed in the smokers' lung

Microbiology and outcomes of community acquired pneumonia in non cystic-fibrosis bronchiectasis patients

Background: It is general belief that Non-cystic fibrosis bronchiectasis (NCFB) is characterized by frequent community-acquired pneumonia. Nonetheless, the knowledge on clinical characteristics of CAP in NCFBE is poor and no specific recommendations are available. We aim to investigate clinical and microbiological characteristics of NCFBE patients with CAP. Methods: Prospective observational study of 3495 CAP patients (2000-2011). Results: We found 90 (2.0%) NCFBE-CAP that in comparison with non-bronchiectatic CAP (n, 3405) showed older age (mean\ub1[SD], NCFBE-CAP 73\ub114 vs. CAP 65\ub119yrs), more vaccinations (pneumococcal: 35% vs. 14%; influenza: 60% vs. 42%), comorbidities (n 652: 43% vs. 25%), previous antibiotics (38% vs. 22%), and inhaled steroids (53% vs. 16%) (p<0.05 each). Streptococcus pneumoniae was the most frequent isolate in both groups (NCFBE-CAP 44.4% vs. CAP 42.7%; p=0.821) followed by respiratory virus, mixed infections and atypical bacteria. Considering overall frequencies of the main pathogens (including monomicrobial and mixed infections) Pseudomonas aeruginosa (15.5% vs. 2.9%; p<0.001) and Enterobacteriaceae (8.8% vs. 2.4%; p=0.025) were more prevalent in NCFBE-CAP patients than in CAP.Despite these clinical and microbiological differences, NCFBE-CAP showed similar outcomes to CAP patients (mortality, length of hospital stay, etc.). Conclusions: NCFBE-CAP patients are usually older and have more comorbidities but similar outcomes than general CAP population. Usual CAP pathogens, such as S. pneumoniae, are also involved in NCFBE-CAP but P. aeruginosa and other Enterobacteriaceae were globally more frequent than in CAP. Therefore, a wide microbiological investigation should be recommended in all NCFBE-CAP cases as well as routine pneumococcal vaccination for prevention of pneumonia

Effectiveness of combination therapy versus monotherapy with a third-generation cephalosporin in bacteraemic pneumococcal pneumonia: A propensity score analysis

Objective: Combining a macrolide or a fluoroquinolone to beta-lactam regimens in the treatment of patients with moderate to severe community-acquired pneumonia is recommended by the international guidelines. However, the information in patients with bacteraemic pneumococcal pneumonia is limited. Methods: A propensity score technique was used to analyze prospectively collected data from all patients with bacteraemic pneumococcal pneumonia admitted from 2000 to 2015 in our institution, who had received empirical treatment with third-generation cephalosporin in monotherapy or plus macrolide or fluoroquinolone. Results: We included 69 patients in the monotherapy group and 314 in the combination group. After adjustment by PS for receiving monotherapy, 30-day mortality (OR 2.89; 95% CI 1.07-7.84) was significantly higher in monotherapy group. A higher 30-day mortality was observed in monotherapy group in both 1:1 and 1:2 matched samples although it was statistically significant only in 1:2 sample (OR: 3.50 (95% CI 1.03-11.96), P = 0.046). Conclusions: Our study suggests that in bacteraemic pneumococcal pneumonia, empirical therapy with a third-generation cephalosporin plus a macrolide or a fluoroquinolone is associated with a lower mortality rate than beta-lactams in monotherapy. These results support the recommendation of combination therapy in patients requiring admission with moderate to severe disease

The Urban-Rural Continuum. The Bioclimatic Approach to Design, Between Past and Future

L’ambiente costruito rurale, insieme multiscalare di trasformazioni praticate dall’uomo per accogliere le attività collegate all’agricoltura, suggerisce varie riflessioni sull’approccio bioclimatico nel progetto di architettura. Il contributo mette subito in evidenza il tema del continuum urbano-rurale (luogo intermedio e contraddittorio che condensa le trasformazioni che stanno avvenendo nella contemporaneità, offrendo un banco di prova necessario per tutti i campi del sapere e per tutte le discipline tecnologiche) per evidenziare che la contrapposizione tra urbano e rurale non solo è superata nei fatti, ma anche è teoricamente inadeguata a identificare l’ambiente costruito rurale, nonostante sia stata utilizzata sin da antico, sui livelli sia analitico che progettuale. Il superamento di tale contrapposizione viene confermato dal legame tra attività agricole e costruttive, di cui viene proposta una lettura in chiave tecnologica, con riferimento alle sfere del prodotto e del processo, dopo averne ricordato le origini culturali remote e profondamente radicate. Il possibile duplice e contraddittorio carattere dell’ambiente costruito rurale, vernacolare o colto, viene illustrato con riferimento alla specificità degli aspetti bioclimatici riconosciuti negli edifici tradizionali (sostenibilità ante litteram), evidenziando come nel XX secolo si sia cancellato il legame con il fattore sito e con la tradizionale cultura costruttiva, creando le premesse per una ingente e diffusa emergenza qualitativa anche per le costruzioni che ospitano attività produttive primarie. Accennando all’interrogativo se oggi abbia senso una precisa tipologia di edificio produttivo rurale e evidenziando l’importanza delle interrelazioni con gli aspetti socioeconomici del settore produttivo dell’agricoltura, il contributo sottolinea che il costruito rurale nel suo insieme contribuisce all’identità ibrida del paesaggio contemporaneo e conclude dimostrando che proprio l’approccio bioclimatico possa svolgere un ruolo di collante, sia teoretico che operativo, perché contribuisce a creare una comune metodologia, adeguata ad affrontare le sfide contemporanee. superando una certa tendenza alla improvvisazione e eccessivi specialismi e facendo leva su opportune azioni di formazione e divulgazione.The rural built environment, as a multiscale whole of human transformations aimed at accommodating agriculture-related activities, prompts various reflections on the bioclimatic approach in architectural design. This contribution, firstly, highlights the theme of the urban-rural continuum (an intermediate and contradictory place, which epitomizes on-going contemporary transformations) in order to demonstrate that the contrast between urban and rural – although it has been used, since ancient times, on both analytical and design level – has not only been superseded, but is also, theoretically, inadequate for identifying the rural built environment. The link between agricultural and construction activities confirms the overcoming of this contrast; a reading in technological terms is proposed, with reference to the spheres of the product and the process, whilst recollecting its remote and deeply rooted cultural origins. The possible dual and contradictory character (vernacular or scholarly) of the rural built environment is illustrated with reference to the specificity of the bioclimatic aspects recognized in traditional buildings (“ante litteram sustainability”), highlighting how the relationship with the site-factor (microclimatic characteristics and local construction culture) was annulled in the 20th century, also creating the basis for a widespread emergency for the quality of the buildings employed in agricultural activities. Touching upon the question of whether the rural building can be a typology distinct from other production buildings, this paper highlights the importance of the relationships with the socio-economic aspects of the agricultural sector, underlining the fact that the main identity for rural buildings in every age, in addition to the role that they play in the landscape, should be a stronger bond with the environmental elements, showing the centrality of the bioclimatic approach in updating the primordial interactions between agriculture and construction. Furthermore, the distinction between vernacular or scholarly character of the rural buildings prompted a reflection on the contemporary epistemological bases of the bioclimatic approach to general architectural design, which risks being ineffective whether it remains on an empirical level or if it is confined to a hyper-specialized niche. Finally, the bioclimatic approach is indicated as a common analytical and design methodological basis, useful for addressing the contradictory nature of the urban-rural continuum, in the framework of contemporary challenges