La finanziarizzazione della natura

Gli studi sul tema della finanziarizzazione nel contesto della questione ambientale hanno proposto descrizioni efficaci dal punto di vista socioeconomico, e il presente elaborato contribuisce alla letteratura esistente ricostruendo la finanziarizzazione della natura dal punto di vista delle strutture giuridiche che la alimentano. A tal fine, individua le coordinate fondamentali del fenomeno, composito e in divenire, nella giuridificazione dei meccanismi di contabilità ambientale, nella costruzione del mercato dei servizi ecosistemici e nella formulazione di modelli innovativi che consolidano la collocazione degli obiettivi di tutela dell’ambiente all’interno delle logiche della finanza. L’elaborato traccia un filo conduttore tra gli approcci delineati nel diritto statunitense, nel diritto internazionale, e nel diritto europeo, restituendo l’immagine non solo di un peculiare percorso di circolazione dei modelli giuridici, ma anche della incalzante affermazione della finanziarizzazione come paradigma

XadA-like adhesin XADA2 regulates biofilm formation in X. fastidiosa subsp. fastidiosa putatively by engaging oleic-acid derived oxylipins

BACKGROUND: The oxylipins 10-HpOME and 7,10-DiHoME derive from oleic acid and have been extensively studied for their ability to regulate contractions, microcolony formation and biofilm formation in the model organism Pseudomonas aeruginosa. METHODS AND RESULTS: Xylella fastidiosa subsp. pauca strain de Donno has been reported to produce 10-HpOME and 7,10-DiHOME in vivo when inoculated in the model plant Nicotiana tabacum or in naturally occurring infected olive trees. In this study, we deciphered the relationship among cell adhesion and oxylipins in Xylella fastidiosa subsp. fastidiosa (Temecula1 strain) and subsp. multiplex (AlmaEM3 strain). The role of the PD0744 gene, encoding for XadA2, a non-fimbrial adhesin belonging to the trimeric autotransporter family, probably involved in the surface attachment required in the initial phase of biofilm formation was investigated. PD0744 deletion mutants in two X. fastidiosa strains were generated, through homologous recombination, and the impact of its deletion on bacterial lifestyle was assessed. In vitro assays were performed to characterize the mutant phenotype, particularly in twitching motility and its capability to grow and form biofilm. Mutants showed a reduced twitching motility and biofilm formation compared to wild type strains. HPLC-MS/MS analysis revealed a decrease in 7,10-DiHOME production together with an increase of its precursor 10-HpOME in the mutants. CONCLUSIONS: 7,10-DiHOME could be a crucial signaling molecule to promote biofilm formation and twitching motility, whose synthesis likely depends on a signal transduction requiring the presence of the adhesin XadA2 and thus not working if this protein is depleted. These results help understanding the complex regulation of biofilm formation in this devastating pathogen

Tildrakizumab and quality of life. deep dive into the impact of psoriasis and treatment on different domains—should psychosocial life impairment be considered a comorbidity

Background/Objectives: Psoriasis is a chronic inflammatory skin disease that may have a significant impact on patients' quality of life. Alongside clinical scores, treatment goals include improvements in patients' quality of life, divided into its social, working and psychosocial life aspects. Indeed, psychological impairment should always be considered in the management of moderate-to-severe psoriasis. Tildrakizumab, an anti-IL-23, is approved for the management of moderate-to-severe psoriasis. Both clinical trials and real-life studies show its efficacy and safety; however, no studies have evaluated how tildrakizumab may improve different domains of quality of life, including physical, psychological, and social aspects of patients' quality of life. The objective was to evaluate the effectiveness of tildrakizumab in the management of moderate-to-severe psoriasis, focusing on the impact on all domains of patients' quality of life. Methods: A 28-week multicenter, real-life, retrospective study was performed enrolling patients affected by moderate-to-severe psoriasis undergoing treatment with tildrakizumab. PASI and DLQI were evaluated at each follow-up (W16, W28). A sub-analysis of each DLQI question evaluated different domains of quality of life, including physical, psychological, and social aspects of patients' quality-of-life. Results: A total of 62 patients were enrolled. At week 28, 97.1%, 85.7%, and 54.3% of patients achieved PASI75, PASI90, and PASI100, respectively. DLQI showed a significant reduction from baseline (20.3 +/- 5.5) to week 28 (0.9 +/- 2.2, p < 0.0001), with up to 82.9% achieving DLQI < 1. Sub-analysis of each question (Q1-Q10) showed a reduction in the value of each answer from baseline to week 28. Conclusions: The results confirm tildrakizumab as an effective and safe treatment in real life, positively affecting all domains of quality of life, with significant impact already appreciable at week 16 of follow-up

A proposal for the physical modeling of ghost geodetic transients

Faults showcase a wide range of possible slip behaviours. After the occurrence of a large earthquake, once the coseismic offset takes place, the slip rates keep high for months or even years as a response to stress redistribution. An exponential fit (or, equivalently, a logarithmic one) is usually performed to reproduce geodetic measurements during the post-seismic phase (Sobrero et al., 2020). However, compelling evidence has been provided recently that the fault slip cycle is more complicated than previously avowed (e.g., Hammond et al., 2021). Long-term post-seismic attenuations have been detected and they are not compatible with classical viscous relaxations (Hearn et al., 2013; Carafa et al., 2024). Here, we would like to face this issue and try to propose a possible physical explanation. We show that in the low-strain regime, i.e., after several weeks after the mainshock, the structural and rheological heterogeneities determine a dynamic slowing-down of the mechanical stabilization of the system. We derive a possible analytical solution for the postseismics also valid in the long run. The result is a long-term “ghost contribution” to geodetic measurements that can last for decades and affecting wide regions. We apply our model to available recent and past GNSS recordings both in Italy and in other countries after appropriate pre-processing to remove spurious and short-term components of geodetic data series. References Carafa M. M., Bird P., Verdecchia A., Taroni M. and Doglioni C.; 2024: Empirical evidence for multi-decadal transients affecting geodetic velocity fields and derived seismicity forecasts in Italy. Sci. Rep., 14(1), 19941. Hammond W. C., Blewitt G., Kreemer C., Koehler R. D. and Dee S.; 2021: Geodetic observation of seismic cycles before, during, and after the 2020 Monte Cristo Range, Nevada earthquake. Seismol. Res. Lett., 92(2A), 647-662. Hearn E. H., Pollitz F. F., Thatcher W. R. and Onishi C. T.; 2013: How do “ghost transients” from past earthquakes affect GPS slip rate estimates on southern California faults? Geochem. Geophys. Geosyst., 14(4), 828-838. Sobrero F. S., Bevis M., Gómez D. D. and Wang F.; 2020: Logarithmic and exponential transients in GNSS trajectory models as indicators of dominant processes in postseismic deformation. J. Geod., 94(9), 84

Prediction and analysis of high-frequency combustion instabilities in liquid rocket engines using low-order modeling

High-frequency combustion instability has consistently posed a significant challenge in the design of new liquid rocket engines, where the potential for engine failure remains an ever-present concern. Although this topic has been extensively studied since the 1950s through a combination of experimental and numerical methods, a comprehensive understanding of the mechanisms underlying the phenomenon and the development of reliable predictive capabilities have yet to be achieved. This thesis addresses the analysis and prediction of different types of high-frequency instability in both single- and multi-injector engines using a multi-dimensional CFD solver for multi-species reactive flows based on low-order modeling. The numerical tool developed for this purpose, known as ``K-AFFS'', incorporates several modeling choices aimed at improving computational efficiency. The approach relies on Eulerian governing equations, on the reduction of combustion products to a single species with properties of the stoichiometric mixture, on the application of a simplified single-step global reaction for the combustion process, and on the implementation of an innovative hybrid-D approach. This approach represents the combustion chamber as a three-dimensional domain, while each injector is modeled as a quasi-one-dimensional domain, with appropriate integration at their interfaces. While the use of simplified physical models may overlook certain critical aspects of thermo-acoustic phenomena, this limitation is accounted for by enforcing them through a submodel, referred to as ``response function''. Traditional response functions establish a direct link between acoustic waves and unsteady heat release, relying heavily on external calibration data and therefore lacking predictive capabilities. On the other hand, K-AFFS employs a physics-based response function that directly links acoustic waves propagating in the injector mixing zone (recess) with the unsteady fuel mass flow rate from the injectors annular gaps. This method is designed to mimic the unsteady behavior observed in shear coaxial injectors, characterized by cyclic fuel accumulation and release. The formulation preserves a possible cause-effect relationship between acoustic waves and unsteady heat release while remaining independent of external data. The approach is validated against three distinct test cases, chosen to encompass a wide range of operating conditions. The first test case, referred to as ``NASA-LeRC'', involves a 178 kN thrust-class engine equipped with 82 recessed shear coaxial injectors which exhibits a transverse spinning instability at the first tangential chamber mode (1T). The validation begins with a preliminary analysis conducted within a reduced quasi-one-dimensional framework for a single-injector configuration, and progresses to a full-scale analysis using a multi-dimensional framework. The study includes sensitivity analyses to examine the impact of model parameters on the results, and further investigates the effect of introducing baffles as damping devices within the combustion chamber. The second test case focuses on the Continuously Variable Resonance Combustor (CVRC), a simple apparatus that exhibits longitudinal instabilities at the first longitudinal mode. This single-injector system features a movable injector head that allows for extensive data collection by varying the length of the injector. Comparative analyses between experimental and numerical data are conducted within a quasi-one-dimensional framework, evaluating 17 different injector lengths. The capabilities of K-AFFS in assessing the chamber stability and in identifying various thermo-acoustic and injection-coupling mechanisms are thoroughly investigated. An in-depth analysis of a stable and of an unstable configuration to identify key factors driving the observed unsteady dynamics is also included. A parametric study is conducted to assess the physical response of the numerical tool and the dependence of the solution quality on the initial model parameter settings. The final test case involves the Brennkammer D (BKD) combustor, a well-documented and extensively studied sub-scale engine known for its transverse standing instabilities at the first tangential mode (1T). This thrust chamber features 42 recessed shear coaxial injectors fed by cryogenic supercritical oxygen and supercritical gaseous hydrogen. Comparative analyses between experimental and numerical data focus on limit cycle features and on the identification of key mechanisms driving the unstable dynamics. A sensitivity analysis is also conducted to verify the physical behavior of the solution and to ensure its minimal dependence on model parameters within a multi-injector framework. The results demonstrate a high level of agreement with experimental data across all three test cases, particularly in terms of limit cycle frequency. The findings provide valuable insights into the phenomena underlying the observed unstable dynamics. K-AFFS consistently proves its ability to accurately detect both stable and unstable conditions and to distinguish between different types of instabilities as well as different wave displacements. The comprehensive validation, together with the sensitivity analyses confirming that the tool predictive capabilities are not heavily reliant on the initial model parameter settings, establishes K-AFFS as a powerful predictive tool with significant potential for application in the design of new liquid rocket engines

Approccio proattivo alla sicurezza dell'infrastruttura stradale mediante valutazione delle condizioni operative del traffico e del contesto territoriale

The research project aims to develop an innovative model for proactive road safety assessment, a critical issue in the management of transport infrastructure. Traditionally, safety improvement strategies have relied on a reactive approach, focused on analysing past accidents, which has proven limited in preventing future incidents. To address these shortcomings, Directive 2019/1936/EU and recent technological advancements advocate for the adoption of predictive models capable of identifying latent risk factors and preventing accidents, thereby enhancing the overall safety of road networks. In this context, the project proposes an advanced methodology for proactive road safety analysis, based on observing operational traffic conditions, particularly actual operating speed, and the surrounding territorial context through a new indicator known as the Settlement Ratio (SR). The research integrates historical accident data, information gathered from probe vehicles (Historical Car Data), and spatial data related to the territory. The use of GIS tools and advanced computational software enables the mapping of both operational and territorial risks, identifying road sections with a higher concentration of incidents. This approach has been applied to selected rural roads managed by ANAS in Italy’s Veneto region, with the aim of providing targeted solutions to improve safety and optimize infrastructure management. The need for a proactive approach is particularly pressing for rural roads, where the number of accidents is lower compared to urban areas, but the mortality rate is significantly higher. The proposed methodology addresses this issue by considering both infrastructure characteristics and surrounding territorial features in an integrated manner. The originality of the project lies in the integration of diverse data sources and multidisciplinary approaches to offer a fresh perspective on road safety analysis. The most innovative aspect is the inclusion of the territorial context as a key factor in risk assessment. Taking settlement characteristics into account allows for tailoring infrastructure planning and management to the specific needs of local communities. Both urban and rural development directly influence traffic flows and require targeted interventions to ensure a safer and more efficient road network. Another distinctive feature of the project is the use of advanced analytical tools to better understand traffic dynamics and user behaviour, enabling the identification of latent risks along the road network. This approach facilitates timely and targeted interventions, improving resource allocation and reducing the likelihood of future accidents. Within the proposed methodology, the Settlement Ratio (SR) plays a pivotal role as an indicator measuring the level of anthropization in the area surrounding a road infrastructure. Unlike traditional tools, the SR provides a continuous representation of settlement conditions along the route, highlighting critical situations resulting from the interaction between infrastructure and territory. This indicator is complemented by the Settled Area (SA), which measures the proportion of built-up area within the study region. This approach provides an innovative tool to optimize road network management by enhancing its performance and adapting it to evolving territorial dynamics. An important future application of this methodology concerns road networks with limited or unavailable accident data. In such cases, a detailed analysis of infrastructural, territorial, and functional characteristics will enable the anticipation of the most common types of accidents, providing a valuable and proactive tool to support the management and planning of road infrastructure. Methodology The proposed methodology is structured into four main phases, each contributing to a holistic understanding of the operational conditions of the road network and the surrounding territorial context. Each phase has been designed to address specific analytical needs, ensuring a systematic and replicable process: 1. Road Network Geometry Analysis The first phase of the methodology involves reconstructing the road network geometry using georeferenced data extracted from the road graph. This process provides an accurate representation of the layout, essential for subsequent analyses. A MATLAB algorithm processes raw data to identify the planimetric elements of the infrastructure: straight sections are recognized as segments with constant azimuth, while circular curves are detected through smoothing techniques based on least squares fitting, which determine their radius and length. Based on the extracted planimetric data, the code generates a curvature diagram and calculates theoretical design speeds in compliance with the 2001 Italian Ministerial Decree. An integrated graph is then produced, overlaying the curvature and speed diagrams, enabling simultaneous analysis of the road layout and associated design speeds. This tool allows for evaluating the consistency between the road alignment and the intended operational conditions. The analysis goes beyond the road layout by including the identification of key infrastructural interferences, such as intersections, access points, bridges, and viaducts, which are critical elements influencing user behaviour and safety conditions. Correct identification of these interferences is essential to assess their impact on traffic dynamics and accident occurrence. The alignment consistency check is based on comparing geometric characteristics with theoretical design speeds. The study of curvature and speeds helps identify potential geometric issues that could compromise operational conditions and user safety. Finally, the integration between infrastructure and territorial context is analysed through the mapping of interferences to evaluate their effect on traffic conditions and the occurrence of accidents. 2. Settlement Analysis and Introduction of the Settlement Ratio (SR) One of the innovative elements of the proposed methodology is the introduction of the Settlement Ratio (SR), an indicator that quantifies the degree of anthropization along road infrastructures. The SR measures the ratio between built-up areas and the total plot surface, integrating building density and land use. This indicator provides a continuous representation of settlement conditions along the route and an assessment of their impact on traffic operational conditions. The SR is divided into four macro-categories: residential, community, infrastructural, and agricultural, offering a detailed view of the functions of buildings and the interactions between infrastructure and territory. The methodology involves the use of georeferenced data processed through GIS software like QGIS, which integrates information on buildings, land cover, and the road graph, and computational tools like MATLAB to implement and process the data. The methodology combines spatial analyses and functional data to provide a detailed and accurate representation of the territorial context. The Settlement Ratio (SR) allows the evaluation of both the number of built-up areas in a specific region and the functions of the buildings, offering a comprehensive measure of the degree of anthropization. This index synthesizes building density and land use characteristics, making it essential for understanding the interactions between the built environment and road infrastructure. Data collection and processing are conducted using QGIS software, which allows for the integration of georeferenced data on buildings, land cover, and the road graph, enabling location-based analyses. The spatial analysis utilizes moving investigation windows, represented by circles with a 500-meter radius centred on road network vertices. This approach systematically identifies all buildings and plots within the area surrounding the analysed road section, ensuring a precise and continuous assessment of settlement conditions along the entire infrastructure. The moving windows ensure a progressive and continuous representation of settlement conditions, placing the road infrastructure at the centre of territorial analysis. The collected data is then subjected to a verification and validation process to ensure quality and reliability for subsequent analyses. The identified buildings are aggregated into a single dataset, and territorial plots are incorporated into their respective new dataset. The data validation includes geometry checks to detect and eliminate errors such as self-intersections and duplicates, as well as the aggregation of information to optimize computational operations and reduce redundancies. The SR calculation is performed in MATLAB and is structured into two main phases. The first phase involves a preliminary calculation of the ratio between the built-up area of a plot and its total surface. The second phase consists of weighting the initial value using a multiplicative coefficient that accounts for the plot size relative to the investigation window. This step ensures that the SR accurately reflects plot characteristics, preventing smaller plots from disproportionately influencing the final results. The final SR value ranges from 0 to 1, where higher values indicate a greater degree of anthropization, signalling a significant presence of buildings and settlements in the analysed territory. A key aspect of the methodology is the classification of land uses. To simplify and optimize the analysis, land uses are grouped into four main macro-categories: • Agricultural: Including areas designated for agricultural activities and natural spaces. • Infrastructural: Covering areas occupied by road, rail, and service infrastructures. • Residential: Refers to areas designated for housing buildings. • Community: Encompassing public, commercial, and industrial structures. This classification allows the specific contribution of each category to the overall SR value to be quantified, providing a detailed view of the different types of settlements along the road route. The analysis results are graphically represented along the examined road sections. The final graph shows the trend of the SR for each macro-category and the percentage of Settled Area (SA), which represents the portion of built-up territory within the investigation windows. This visualization makes it easy to identify areas with high building density and understand how urbanization impacts road infrastructure operational conditions, providing essential support for road network planning and management. The second phase of the proposed methodology enables a detailed analysis of settlement characteristics along specific road sections, using graphs that illustrate the Settlement Ratio (SR) and the Settled Area (SA). These analytical tools help understand the distribution and density of buildings along roadways, highlighting how roads cross areas with varying building densities, alternating between urbanized zones and rural contexts. Peaks in SA are significant near urban centres, where high SR values for community and residential categories are prevalent, while they decrease in more rural areas. However, even in extra-urban zones, the indices are not negligible, indicating that road infrastructures are influenced by anthropization even in the absence of urban centres. The conducted analysis provides a refined and validated dataset essential for rigorous spatial analysis, useful both for understanding settlement distribution along roads and for improving territorial planning. The proposed methodology identifies areas where urbanization significantly impacts road infrastructures, providing operational support for territorial management. Understanding the distribution and intensity of settlements along roadways is crucial to ensure that residential and community areas are adequately served by infrastructure and services, promoting balanced and sustainable territorial development. This methodology also allows for analysing territorial dynamics with a proactive approach, identifying critical points where high surrounding settlement levels can influence operational conditions and road safety. Areas with high SR values tend to present more complex traffic dynamics, potentially increasing accident risk. In this sense, integrating accident history analysis can provide valuable information for developing targeted road infrastructure management strategies. The methodological approach described also serves as a useful tool for future planning. By identifying rapidly expanding areas or zones at risk of congestion, it is possible to anticipate infrastructure needs and plan timely interventions to improve road capacity and reduce the likelihood of accidents. Risk prediction and management are essential to ensure sustainable infrastructure development in response to population growth. Analysing SR variations is a key element for improving safety and efficiency in long-term road planning. 3. Operational Speed Analysis In the third phase, operational speeds along the road network are analysed. This process relies on historical data collected through probe vehicles, processed using MATLAB to generate a continuous speed profile that reflects actual user behaviour. The analysis identifies discrepancies between regulatory design speeds and the speeds drivers adopt, pinpointing critical sections where road geometry or functionality leads to deviations from expected driving behaviour. To assess mobility and the operational efficiency of road infrastructure, Historical Car Data (HCD) provided by Infoblu, a company within the Atlantia Group, were utilized. The dataset, gathered from roads in the Veneto region, includes approximately 11.5 million speed measurements recorded during three specific periods: August 2018, February 2019, and May 2019. The goal of the analysis was to evaluate traffic conditions by constructing an operational speed profile, defined as the 85th percentile (V85) of speeds practised by users under ideal conditions. The reconstruction of operational speeds began with data management using MySQL Workbench. The map-matching technique was applied to project GPS coordinates onto road graphs. The data were then divided by travel direction (South-North and North-South) and filtered to create a precise speed profile. This filtering process excluded data influenced by adverse weather or traffic conditions, ensuring a reliable assessment of driving behaviour along the monitored sections. The analysis showed that the studied road sections operated under free-flow traffic conditions, without significant congestion. The data were further segmented into two main periods: daytime and nighttime. This segmentation enabled the creation of a geolocated dataset along the road’s curvilinear reference line, useful for developing a continuous speed profile using the smoothing cubic spline technique. Comparing operational speed profiles between daytime and nighttime periods revealed notable differences in driver behaviour, influenced by traffic density, road geometry, and risk perception. During nighttime hours, operational speeds tended to be higher than those recorded during the daytime, primarily due to reduced traffic congestion and a diminished perception of risk, leading drivers to adopt less cautious behaviour. However, in sections with restrictive geometry or specific territorial conditions, speed reductions were observed even at night to maintain safety. Conversely, daytime operational speeds were generally lower than at night. This difference was particularly evident in extra-urban industrial areas, where heavy traffic and work-related activities negatively affected speeds, resulting in values below theoretical design speeds. These discrepancies were most pronounced during weekday time slots, when industrial traffic intensity was at its peak, causing noticeable slowdowns in vehicle flow. The comparison between operational and theoretical speeds showed frequent deviations from expected values. Graphical representations helped identify critical sections of the road network where real operational conditions did not align with design assumptions. These deviations were attributed to a combination of geometric, environmental, and behavioural factors that influence driving behaviour and may increase accident risk. The speed profile analysis confirmed that variations between operational and theoretical speeds were driven by infrastructure characteristics, environmental conditions, and visibility factors. These discrepancies indicate that drivers adjust their behaviour to match real-world road conditions, modifying their speeds in response to contextual cues. The insights gained from this analysis are essential for developing targeted traffic management strategies tailored to daytime and nighttime conditions. These strategies aim to enhance road safety and improve the overall efficiency of infrastructure operations. Monitoring critical sections helps identify areas where inconsistencies between user expectations and road characteristics may pose safety risks. In such cases, targeted corrective measures are necessary to ensure safer conditions, reduce accident likelihood, and improve the overall driving experience. 4. Accident Analysis through Kernel Density Estimation (KDE) Analyzing accident data is essential for identifying critical points along the road network and understanding the factors influencing infrastructure safety. To obtain a continuous spatial representation of risk, the proposed methodology employs Kernel Density Estimation (KDE), a non-parametric statistical tool that estimates the probability density of accidents along the road network. This approach overcomes the limitations of point-based analyses by focusing not only on the locations where accidents have occurred but also on surrounding areas that may be at risk. The application of the KDE function represents accident data as a continuous curve rather than a collection of isolated points. This representation extends the safety analysis to the entire road network, maintaining a non-zero accident density value even in sections where no accidents have been recorded but which may still be exposed to potential risks. This approach reflects the idea that accidents are not isolated events but rather the culmination of a risk process that begins upstream of the critical point along the infrastructure. By qualitatively evaluating the KDE curve, it is possible to identify accident peaks corresponding to high concentrations of incidents and analyze the extent of the “bell shapes,” which highlight risk influences both upstream and downstream of the critical point. This analysis identifies areas requiring priority interventions, providing a solid foundation for planning maintenance and infrastructure improvements. Although the proposed methodology is proactive and based on future risk predictions, the validation of the research project required the use of historical accident data. These data allowed for the analysis of recurring events and the evaluation of the impact of infrastructural characteristics on risk factors along the road network. Historical data analysis revealed a strong pattern between accident types and the geometric, environmental, and traffic conditions associated with each road section. One notable finding was the homogeneity of accident profiles observed in sections with similar characteristics. This made it possible to associate specific accident types with each homogeneous road section, identifying recurring risk patterns. The analysis used georeferenced accident data provided by ANAS S.p.A., related to incidents recorded in the Veneto region between 2015 and 2019. The data were imported into QGIS and positioned according to the WGS84 reference system, then converted to the Gauss-Boaga system to ensure compatibility with the road graph used in subsequent MATLAB analyses. During the map-matching process, each accident event was associated with its corresponding position along the road network, and essential information (geolocation, nature, and severity of the incident) was filtered and stored in the accidents.mat file. The KDE processing in MATLAB generated a continuous profile of accident hotspots across the road network. This method identifies spatially distributed critical points, including sections surrounding accident points as potentially at risk. This approach surpasses traditional analyses, which focus solely on precise accident coordinates, offering a more comprehensive and dynamic view of criticalities along the road network. Building a continuous profile of accident density enables the identification of distributed risk areas along the road network, facilitating the planning of proactive interventions. The KDE curve broadens the analysis to include potentially risky sections, even in the absence of concentrated accident clusters, emphasizing the role of infrastructural, environmental, and behavioural factors. In particular, directly comparing the accident density curve with operational speed and settlement profiles identifies road sections with the highest exposure to accident risk. This approach highlights critical sections where operational conditions or territorial configurations influence user behaviour, increasing the likelihood of incidents. The proactive approach correlates accident density data with geometric, infrastructural, and behavioural factors, providing a comprehensive understanding of risk dynamics across the road network. This analysis is fundamental for planning and programming targeted interventions aimed at eliminating or mitigating risk factors present along the road. In conclusion, th

SARS-CoV-2 XEC: A Genome-Based Survey

Recombination, a process of genetic exchange between distinct organisms, has played a critical role in the emergence of SARS-CoV-2 variants such as the XEC recombinant. This study provides a detailed genomic and structural characterization of XEC, derived from the recombination of lineages KP.3.3 (donor) and KS.1.1 (acceptor). Phylogenomic analyses reveal that XEC and its descendant XEC.1 form a monophyletic clade with close evolutionary ties to KP.3.3. The genomic breakpoint, spanning nucleotide positions 22,363–22,463, marks the shift from KS.1.1 to KP.3.3 within the spike protein gene. Mutational analysis highlights shared traits with its parental lineages, including mutations associated with immune evasion, receptor affinity, and fusogenicity. Notable changes, such as Q493E and L455S, may confer unique immunogenic properties, though XEC’s overall immune escape potential is limited by the absence of new mutations in conserved epitopes. Despite these mutations, XEC demonstrates restricted geographical spread, low genetic variability, and an evolutionary trajectory indicative of an evolutionary dead-end. Bayesian Skyline Plot analysis corroborates this, showing stable but declining population size. These findings underscore the need for ongoing genomic surveillance to monitor recombinant variants’ characteristics and public health impact. This study contributes to understanding viral evolution and highlights the importance of distinguishing variants of concern from those with minimal epidemiological significance

Come ci vediamo e come ci vedono gli altri. Un’analisi empirica sulla rappresentazione dell’expertise sociologica in contesti di crisi

L’elaborato propone uno studio sulle rappresentazioni delle funzioni della sociologia e di come viene percepito il ruolo del sociologo, in qualità di esperto, in contesti di crisi. La storia più recente si caratterizza per il rapido susseguirsi, in alcuni casi fino al sovrapporsi, di differenti stati di crisi, eventi che irrompono nella quotidianità degli individui, e in generale della società, scardinandone gli equilibri. Si pensi, ad esempio, alla pandemia da Covid-19, crisi sanitaria senza precedenti che ha mutato il modo di vivere delle persone in tutto il mondo. Oppure, ai conflitti armati come, ad esempio, quello Russo – Ucraino o quelli in Medio Oriente che, oltre alle tragiche conseguenze per le parti coinvolte sul campo, destabilizzano gli equilibri geopolitici tra i vari Paesi del mondo. Gli esempi di eventi di crisi riguardano anche quelli di carattere ambientale, soprattutto rispetto alle conseguenze dettate dal cambiamento climatico. Scenari di crisi come quelli citati costituiscono lo sfondo nel quale si inseriscono i percorsi conoscitivi, teorici ed empirici, intrapresi nel progetto di ricerca. Ed è in tali scenari che si rivela centrale l’intervento degli esperti, cioè individui equipaggiati con una profonda conoscenza in uno specifico campo del sapere, cioè l’expertise, che può rivelarsi determinante nell’elaborazione di adeguate strategie risolutive con cui affrontare la complessità di un evento crisi. L’obiettivo perseguito con il lavoro di ricerca presentato consiste nel comprendere quali sono le rappresentazioni delle funzioni che un sociologo può esercitare in un contesto di crisi in virtù della sua expertise. Per raggiungere tale obiettivo cognitivo, sono state analizzate due differenti prospettive del tema indagato. La prima è una prospettiva esterna al campo sociologico, cioè di coloro che non appartengono alla comunità sociologica. La seconda è invece interna, e riguarda il punto di vista di sociologi e sociologhe che applicano la propria expertise sociologica nelle proprie esperienze di ricerca e professionali. Tali prospettive hanno dato origine alle due fasi empiriche presenti nel disegno della ricerca, fasi distinte ma complementari, in un approccio mixed methods. La prima fase della ricerca è costituita dalla somministrazione di un questionario online in cui, oltre a quesiti sociodemografici, sono state inserite cinque storie narranti ciascuna un differente contesto di crisi immaginario, il quale trae però ispirazione da una crisi realmente accaduta. Ciascuna storia è seguita dalle medesime tre domande, proposte nello stesso ordine, con le quali si chiede ai rispondenti di scegliere, da una lista presentata in cui figura anche l’expertise sociologica, gli esperti, secondo loro, maggiormente indicati a risolvere ciascuna crisi e di motivare tali scelte. Le cinque storie differiscono per la natura della crisi raccontata ma condividono la medesima struttura narrativa, il cui scopo è far immedesimare il rispondente nello scenario narrato. Il questionario è stato rivolto a studenti universitari, provenienti da diverse Università italiane, di diversi corsi di studio e appartenenti ad eterogenei settori scientifico-disciplinari, studenti di dottorato, di scuole di specializzazione e master, scelti poiché interpareti in qualità di esperti in formazione. Dalle 332 risposte raggiunte, sono state rilevate le rappresentazioni delle funzioni della sociologia che, secondo i rispondenti, gli esperti sociologi possono esercitare nella risoluzione della crisi. I risultati del questionario costituiscono inoltre il punto di giunzione con la seconda fase della ricerca, nella quale sono state condotte dodici interviste in profondità a esperti sociologi e sociologhe scelti poiché hanno applicato la propria expertise sociologica nell’elaborazione di strategie risolutive in circostanze di crisi. Nel corso di ciascuna intervista, sono stati mostrati i risultati della precedente fase e, nello specifico, è stato chiesto agli intervistati e alle intervistate di esprimere le loro considerazioni in merito alle rappresentazioni delle funzioni della sociologia emerse dall’analisi delle risposte al questionario. Durante le interviste, sono stati esplorati ulteriori temi che interessano, più da vicino, l’expertise sociologica e di come questa viene oggi percepita, sia da una prospettiva interna alla comunità, e sia esternamente ad essa. I risultati delle analisi condotte mostrano alcuni punti di sovrapposizione tra le due prospettive. I sociologi e le sociologhe intervistati/e hanno riconosciuto alcune delle funzioni richiamate dai rispondenti al questionario come appartenenti all’expertise sociologica. Allo stesso modo però, dalle interviste emergono delle divergenze con le rappresentazioni degli studenti rispondenti poiché non sono emerse, dalle opinioni dei rispondenti, delle funzioni che invece appartengono all’expertise sociologica. In considerazione di quanto rilevato, emerge una non completa sovrapposizione tra le prospettive interpretative, esterna e interna alla sociologia, prese in esame. Al di fuori, la sociologia è percepita come una disciplina dai confini opachi diversamente da altre expertise che risultano più riconoscibili. Dalla prospettiva interna, la disciplina sociologica non si caratterizza per una coesa identità disciplinare. L’elaborato si propone dunque come occasione di riflessione sullo stato della sociologia e di come questa è percepita, da una prospettiva interna ed esterna alla disciplina

Aspetti morfologici, ultrastrutturali e molecolari dell’interazione tra lipofagia, lipasi acida lisosomiale e colestasi nell’epatopatia steatosica non alcolica (NAFLD)

Introduzione La malattia epatica steatosica non alcolica (NAFLD) è caratterizzata da un eccessivo accumulo di lipidi all'interno degli epatociti che conduce ad infiammazione epatica e fibrosi. La disfunzione dell’autofagia ovvero del processo mediante il quale la cellula elimina i cataboliti attraverso i lisosomi, è uno dei meccanismi fisiopatologici che portano all’accumulo di lipidi nella NAFLD. La lipofagia è il meccanismo autofagico attraverso il quale la cellula elimina le gocciole lipidiche costituite da esteri del colesterolo e trigliceridi attraverso il catabolismo lisosomiale. Nel lisosoma la lipasi acida lisosomiale è l’enzima preposto al catabolismo degli esteri del colesterolo. Un altro percorso di eliminazione di colesterolo e fosfolipidi per l’epatocita è costituito dalla loro secrezione nella bile. Dati emergenti suggeriscono che la colestasi in pazienti NAFLD rappresenti un fattore predittivo di prognosi sfavorevole, indicando un ruolo potenziale dell'alterata secrezione biliare nella patogenesi e nella progressione della malattia. Recenti studi hanno evidenziato che la lipofagia può essere disregolata dagli acidi biliari che esercitano un effetto inibitorio (CholeSTOPhagy) in corso di patologie colestatiche. Obiettivo dello studio: In una coorte di pazienti NAFLD abbiamo voluto valutare se fosse presente un impairment lipofagico e se questo fosse correlato a segni di colestasi e/o di disfunzione lisosomiale. Metodi: Abbiamo innanzitutto valutato il contenuto e l'attività della LAL in modelli sperimentali in vitro e in vivo di NAFLD. In totale, sono stati inclusi nello studio 87 pazienti sottoposti a biopsia epatica. Tramite metodiche di immunoistochimica si sono valutate l’espressione di LAL, LAMP1 (marcatore lisosomiale), p62/SQSTM1 (marcatore di impairment autofagico), CK7 (per la valutazione della componente colestatica: cellule epatiche progenitrici HPC ed epatociti intermedi IH), CD-10 (per la valutazione dei canalicoli biliari). E’ stata eseguita un’analisi al micrscopio elettronico a trasmissione per la valutazione delle componenti autofagiche e i segni epatocellulari di colestasi. In un sottogruppo di 38 pazienti tramite la metodica di Nanostring nCounter si è analizzata l’espressione genica di 20 geni coinvolti implicati nel processo autofagico (compresa l’espressione di LAL) e nella secrezione biliare di colesterolo. Risultati Abbiamo evidenziato una riduzione dell’attività di LAL nel modello cellulare 6 di NAFLD. La diminuzione dell'attività di LAL è mediata dall'ubiquitinazione e la proteina ubiquitinata presenta una localizzazione extralisosomiale. In vivo il contenuto epatico di LAL totale è più elevata nei fegati dei pazienti con punteggio NAS 3-5 e 6-7 rispetto a quelli con punteggio NAS 0-2. L'espressione del gene di LAL è risultata lievemente aumentata nei pazienti con NAFLD rispetto ai controlli sani. Dallo studio è emerso un blocco della machinery autofagica con un aumento dell’espressione di p62/ SQSTM1 che correla significativamente con fibrosi e NAS (p=0.01 R=0.322; p=0.01 R=0.157). Nei pazienti con NAFLD sono stati evidenziati lisosomi con lume visibile e sono stati identificati alla TEM come lipolisosomi. L’ accumulo anomalo di LAL ubiquitinata correla con il NAS e con il numero di lipolisosomi (p=0.04, R=0.128). La compromissione dell'autofagia è stata associata ad alterazioni legate alla colestasi nel compartimento biliare: è stato osservato un aumento della reazione duttulare e l'espansione di epatociti intermedi. Si è infatti osservato un aumento parallelo del marcatore di compromissione dell'autofagia p62/SQSTM1 e delle cellule progenitrici epatiche (HPCs) e delle degli epatociti intermedi (IH)(R=0.392, p=0.016; R=0.370, p=0.026) All’analisi ultrastrutturale con il microscopio elettronico a trasmissione si sono evidenziate significative differenze a livello dei canalicoli biliari tra pazienti con NAFLD lieve e severa. Inoltre abbiamo osservato una riduzione dell’espressione di ABCG5/8 con l’aumentare del balooning nei pazienti con colestasi. Conclusioni Nei pazienti NAFLD si assiste ad un impairment della lipofagia con aumento di lisosomi repleti di lipidi non catabolizzati chiamati lipolisosomi. La riduzione dell’attività di LAL sembra possa contribuire alla disfunzione lisosomiale. Inoltre una colestasi a livello istologico ma non sierologico correla con la disfunzione autofagica e con un fenotipo di malattia più severo

Intelligenza artificiale e tecniche avanzate di risonanza magnetica nella valutazione delle alterazioni cerebrali ultrastrutturali nei pazienti affetti da sclerosi multipla in terapia con Tysabri©

Introduzione. La Sclerosi Multipla (SM) è una malattia infiammatoria cronica del sistema nervoso centrale, i cui decorsi clinici sono stati classicamente divisi in 4 forme: Relapsing-Remitting, Primary Progressive, Secondary Progressive (SP) e Progressive Relapsing (PR). Recenti evidenze hanno dimostrato tuttavia come questa classificazione non è in grado di definire come avviene la progressione di disabilità. Per questo nel 2019 sono state introdotte due nuove definizioni: RAW (relapse associated worsening) intesa come progressione di malattia dipendente dalle ricadute, PIRA (progression indipendent from relapse activity) ovvero progressione indipendente dalle ricadute. Con l’introduzione dei disease modyfing therapy, tra cui il Natalizumab (Tysabri©), si è assistito ad una riduzione delle ricadute e conseguentemente della RAW nei pazienti con SM. Al contrario permane la PIRA, il cui substrato patogenetico non del tutto chiaro, così come non sono stati identificati univoci marker di neuroimaging correlabili a questo tipo di progressione. In questo ambito la letteratura più recente si è concentrata sul ruolo dell’intelligenza artificiale e di tecniche di neuroimaging avanzate quali il resting state fuctional MRI e il DTI. Obiettivi. Lo studio ha avuto come obiettivo primario quello di valutare il pattern volumetrico cerebrale nei pazienti in terapia con Natalizumab con PIRA e Clinicamente stabili (CS). Come obiettivi secondari: confrontare lo stato di funzionalità cerebrale a riposo, attraverso un’analisi di rs-fMRI, e lo stato ultrastrutturale di bianca, attraverso analisi di TBSS, sia tra i pazienti clinicamente classificati con PIRA e come CS che tra i gruppi di pazienti eventualmente riclassificati sulla base di uno specifico pattern volumetrico individuato dalla IA. Materiali e Metodi. Studio pilota caso-controllo monocentrico in cui sono stati reclutati 30 pazienti con SM in terapia con Tysabri, (16 PIRA, 14 CS). I soggetti sono stati valutati clinicamente (scale EDSS e SDMT) e hanno effettuato una RM dell’encefalo includente sequenze 3D FLAIR, T1 3D BRAVO, rs-fMRI e DTI. L’analisi volumetrica cerebrale è stata effettuata attraverso il software di IA Pixyl.Neuro.BV; l’analisi di rs-fMRI è stata effettuata attraverso il programma CONN e l’analisi di TBSS attraverso FSL. Le analisi statistiche sono state effettuate con test statistici parametrici, con p value <0,05 come soglia di significatività. Risultati: Dei 30 pz 6 sono stati esclusi per scarsa qualità delle sequenze 3D T1, con risultanti 24 pazienti analizzati (14 PIRA, 10 CS). I risultati di IA hanno evidenziato una maggior frequenza, statisticamente significativa, di atrofia talamica sinistra (ATsn) nel gruppo PIRA rispetto ai CS e hanno permesso una riclassificazione dei pazienti in due gruppi ATsn e senza ATsn. Clinicamente i due gruppi non mostravano differenze in termini di declino cognitivo (valutato con SDMT). L’analisi di rs-fMRI non ha mostrato differenze significative di connettvità funzionale a riposo tra i gruppi PIRA e CS; mentre ha mostrato una riduzione di connettività tra il giro del cingolo posteriore e delle regioni temporo-occipitali destre (giro linguale, fusiforme, ippocampo e paraippocampo) nei soggetti con ATsn rispetto a quelli senza atrofia talamica. I gruppi ATsn e noATsn mostravo differenze cliniche cognitive evidenziate alla valutazione con SDMT. L’analisi di TBSS ha evidenziato un danno microstutturale di sostanza bianca in termini di FA sia nei soggetti PIRA che con ATsn rispetto ai corrispettivi gruppi di controllo. Conclusioni. Pixyl.Neuro.BV ha permesso di riconoscere il grado di atrofia delle strutture cerebrali nei singoli pazienti, ha permesso di individuare l’atrofia talamica sinistra come pattern volumetrico di atrofia ricorrente nei pazienti PIRA. I soggetti classificati dall’IA con ATsn hanno mostrato una ridotta connettività funzionale a riposo in aree deputate a funzioni cognitive, correlata anche a ridotte performance cognitive riscontrate dall’analisi clinica (SDMT). Sia i soggetti PIRA che i soggetti classificati come con ATsn hanno mostrano danni microstrutturali di sostanza bianca in termini di alterata FA come se l’atrofia talamica possa essere conseguente a fenomeni di degenerazione Walleriana