Nuovi biomarcatori di danno renale acuto in terapia intensiva

AKI (Acute Kidney Injury) : Danno renale acuto è una sindrome caratterizzata da una rapida perdita della funzione del rene ed è di solito diagnosticata dall'accumulo di prodotti finali del metabolismo dell'azoto (urea e creatinina) o dalla riduzione della produzione di urina, o entrambi. Nella pratica clinica attuale, AKI è di solito diagnosticata misurando la creatinina sierica. Purtroppo la creatinina è un indicatore tardivo della funzione renale. In primo luogo, i suoi livelli possono variare notevolmente con l'età, il sesso, la massa muscolare, il metabolismo muscolare, i farmaci e lo stato di idratazione del paziente. Inoltre, i livelli sierici di creatinina possono risultare alterati quando ormai si è già perso circa il 50% della funzione renale. In terzo luogo, a tassi più bassi di filtrazione glomerulare, la secrezione tubulare di creatinina sovrastima la funzione renale. Pertanto l’identificazione di nuovi biomarcatori AKI è stata designata come una priorità assoluta da parte della Società Americana di Nefrologia. Scopo di questo lavoro è valutare l’accuratezza diagnostica di nuovi biomarker, come Ngal, Cistatina C, beta2-microglobulina e beta trace protein, al fine di poter diagnosticare e trattare precocemente una condizione di danno renale acuto

Animalia nell'arte contemporanea: studio, conservazione e restauro.

L’elaborato affronta le problematiche del restauro e della conservazione delle opere d’arte contenenti animalia, ossia elementi animali non convenzionali. Il capitolo I raccoglie una classificazione di tutti gli elementi animali utilizzati in arte (Animali interi, Parti di animali, Derivati di animali), mostrandone la diffusione ed il metodo di utilizzo attraverso una rassegna di opere per ogni elemento, dal dadaismo ai giorni nostri. Il capitolo II affronta dieci casi di intervento di varia natura su opere d’arte con animalia (restauro, trasposto, allestimento, immagazzinamento, conservazione preventiva, ecc), con osservazioni sulla storia conservativa dell’opera e l’analisi della tipologia di intervento eseguita. Il capitolo III affronta le problematiche generali del restauro e della conservazione di opere d’arte contenenti elementi animali, attraverso un’analisi delle difficoltà incontrate nella ricerca per il capitolo I e una lettura trasversale delle schede di intervento del capitolo II. La tesi ha lo scopo di valutare lo stato dell’arte del restauro e della conservazione di opere contenenti animalia, di individuare la bibliografia disponibile e creare un ponte con discipline esterne alla storia dell’arte che possono fornire informazioni importanti in proposito, di individuare le metodologie di intervento varie ed eterogenee utilizzate fino ad oggi

Verifying safety properties of a nonlinear control by interactive theorem proving with the Prototype Verification System

Interactive, or computer-assisted, theorem proving is the verification of statements in a formal system, where the proof is developed by a logician who chooses the appropriate inference steps, in turn executed by an automatic theorem prover. In this paper, interactive theorem proving is used to verify safety properties of a nonlinear (hybrid) control system

Formal Verification in the Loop to Enhance Verification of Safety-Critical Cyber-physical Systems

Formal verification may play a central role in the development of safecontrollers, such as those found in electric drives or (semi-)autonomousvehicles, whose complexity arises from the coexistence ofmechanical and electrical subsystems with sophisticated electronic controllersthat must implement high-level control policies according to different drivingmodes, while optimizing several objectives, such as safety first and foremost,efficiency, and performance among others.  Model-driven development resorts tosimulation to assess how well the various requirements and constraints aresatisfied, but there is a growing awareness that more rigorous methods areneeded to achieve the required levels of safety.  This paper proposes aconceptual framework for the development of complex systems based on (i)higher-order logic specification, (ii) verification by theorem proving, and(iii) tight integration of verification with model-driven development andsimulation.  This framework addresses both digital and analog systems, asillustrated with some examples in different fields including implantablebiomedical systems, autonomous vehicles, and electric valve actuation

A Review on Active 3D Microstructures via Direct Laser Lithography

Direct laser lithography (DLL) is a key enabling technology for 3D constructs at the microscale and its potential is rapidly growing toward the development of active microstructures. The rationale of this work is based on the different involved methodology, which is referred as indirect, when passive microstructures become active through postprocessing steps, and direct, when active structures are directly obtained by fabricating microstructures with active materials or by introducing heterogeneous mechanical properties and specific design. An in‐depth analysis of both indirect and direct methods is provided. In particular, the wide range of materials and strategies involved in each method is reported, including advantages and disadvantages, as well as examples of fabricated structures and their applications. Finally, the different techniques are briefly summarized, and critically discussed by highlighting how the new synergies between DLL and active materials are opening completely new scenarios, in particular for sensing (e.g., mechanical) and actuation at the microscale

Towards a Formalization of System Requirements for an Integrated Clinical Environment

Interoperability of medical devices, and their interface to clinicians and patients, are critical issues for the safety and effectiveness of patient care. Ongoing efforts strive at establishing standards for integrated clinical environments, which may connect and co-ordinate several medical devices and interface them to patients, clinicians, and hospital information systems. In this paper, an approach to the formalization of system requirements for an integrated clinical environment is presented. The formalization relies on the higher-order logic language of the Prototype Verification System

A PVS-Simulink Integrated Environment for Model-Based Analysis of Cyber-Physical Systems

This paper presents a methodology, with supporting tool, for formal modeling and analysis of software components in cyber-physical systems. Using our approach, developers can integrate a simulation of logic-based specifications of software components and Simulink models of continuous processes. The integrated simulation is useful to validate the characteristics of discrete system components early in the development process. The same logic-based specifications can also be formally verified using the Prototype Verification System (PVS), to gain additional confidence that the software design complies with specific safety requirements. Modeling patterns are defined for generating the logic-based specifications from the more familiar automata-based formalism. The ultimate aim of this work is to facilitate the introduction of formal verification technologies in the software development process of cyber-physical systems, which typically requires the integrated use of different formalisms and tools. A case study from the medical domain is used to illustrate the approach. A PVS model of a pacemaker is interfaced with a Simulink model of the human heart. The overall cyber-physical system is co-simulated to validate design requirements through exploration of relevant test scenarios. Formal verification with the PVS theorem prover is demonstrated for the pacemaker model for specific safety aspects of the pacemaker design

Modeling communication network requirements for an integrated clinical environment in the Prototype Verification System

Health care practices increasingly rely on complex technological infrastructure, and new approaches to the integration of information and communication technology in those practices lead to the development of such concepts as integrated clinical environments and smart intensive care units. These concepts refer to hospital settings where therapy relies heavily on inter-operating medical devices, supervised by clinicians assisted by advanced monitoring and co-ordinating software. In order to ensure safety and effectiveness of patient care, it is necessary to specify the requirements of such socio-technical systems in the most rigorous and precise way. This paper presents an approach to the formalization of system requirements for communication networks deployed in integrated clinical environment, based on the higher-order logic language of a theorem-proving environment, the Prototype Verification System

Surgical treatment of sporadic vestibular schwannoma in a series of 1006 patients. Trattamento chirurgico degli schwannomi vestibolari: risultati su una serie di 1006 pazienti

La gestione dello schwannoma vestibolare (SV) sporadico si è gradualmente evoluta negli ultimi decenni. Lo scopo di questo studio è di analizzare l’evoluzione negli esiti chirurgici dell’exeresi di queste lesioni, realizzata da un team neurotologico tra il 1990 e il 2006, attraverso differenti approcci. È stata eseguita una revisione retrospettica monocentrica dei dati clinici di 1006 pazienti. Al fine di valutare eventuali modifiche e progressi, il periodo di 17 anni è stato diviso in tre periodi, ciascuno comprendente rispettivamente 268 SV (1990- 1996), 299 SV (1997-2001), e 439 SV (2002-2006). Il follow-up medio è stato di 5,9 ± 2,4 anni. Complessivamente l’asportazione totale è stata ottenuta nel 99,4% dei casi. Il tasso di mortalità è stato dello 0,3%, la meningite e la perdita di liquido cefalo rachidiano (LCR) sono stati osservati nel 1,2% e il 9% dei casi, rispettivamente. La frequenza della perdita di LCR è diminuita dal 11,6% al 7,1% tra il primo e dell’ultimo periodo (p < 0,01) e la revisione chirurgica dal 3,4% al 0,9% (p < 0,05). Il nervo facciale è stato anatomicamente conservato nel 97,7% dei casi. Ad un anno, una buona funzione del nervo facciale è stata osservata nel 85,1% dei pazienti (I e II grado HouseBrackmann), con una variazione tra il primo e l’ultimo periodo che andava dal 78,4% al 87,6% (p < 0,05). Ad un anno post-operatorio la conservazione dell’udito è stata ottenuta nel 61,6% dei pazienti, passando dal 50,9% del primo periodo, al 69,0% del periodo piú recente (p < 0,05) (classe A + B + C dalla classificazione AAO-HNS). L’udito utile (classe A + B) è stato conservato nel 33,5% dei casi complessivamente, con percentuali comprese tra il 21,8% e 42% nel primo e nell’ultimo periodo rispettivamente (p < 0,01). Gli esiti chirurgici dell’asportazion dello schwannoma vestibolare sporadico sono migliorati negli anni per quanto riguarda i risultati funzionali del nervo facciale, la conservazione dell’udito, le perdite di liquido cefalorachidiano, principalmente grazie all’esperienza del team neurotologico. I risultati funzionali dopo la rimozione microchirurgica completa SV di grandi dimensioni dipendono dall’ esperienza maturata sulle lesioni di piccole dimensioniThe management of sporadic vestibular schwannoma (VS) has evolved in the last decades. The aim of this study was to analyse the evolution in surgical outcomes of VSs operated by a neurotological team between 1990 and 2006 by different approaches. A monocentric retrospective review of medical charts of 1006 patients was performed. In order to assess eventual changes and progress, the 17-years period was divided in three periods, each one comprehending 268 VS (1990-1996), 299 VS (1997-2001), and 439 VS (2002-2006). Mean follow-up was 5.9 ± 2.4 years. Overall, complete VS removal was achieved in 99.4% of cases. Mortality rate was 0.3%, meningitis and CSF leaks were observed in 1.2 % and 9 % of the cases, respectively. CSF leakage decreased from 11.6% to 7.1% between the first and last period (p < 0.01) as well as revision surgery from 3.4 % to 0.9 % (p < 0.05). Facial nerve was anatomically preserved in 97.7% of cases. At one year, a good facial nerve function was observed in 85.1% of patients (grade I and II of House-Brackmann grading scale), which ranged between the first and last period from 78.4% to 87.6% (p <0.05). At one year, hearing preservation was obtained in 61.6% of patients, which increased from the first period to the last one from 50.9% to 69.0% (p < 0.05) (class A+B+C from the AAO-HNS classification). Useful hearing (class A+B) was observed in 33.5% of cases overall, with 21.8% and 42% in the first and last period, respectively (p < 0.01). Surgical outcomes of sporadic vestibular schwannoma have improved concerning facial nerve function outcomes, hearing preservation and cerebrospinal fluid (CSF) leaks, mainly due to the neuro-otological team's experience. Functional results after complete microsurgical removal of large VS depend on experience gained on small VS removal

Co-simulated digital twin on the network edge: A vehicle platoon

This paper presents an approach to create high-fidelity models suited for digital twin application of distributed multi-agent cyber–physical systems (CPSs) exploiting the combination of simulation units through co-simulation. This approach allows for managing the complexity of cyber–physical systems by decomposing them into multiple intertwined components tailored to specific domains. The native modular design simplifies the building, testing, prototyping, and extending CPSs compared to monolithic simulator approaches. A system of platoon of vehicles is used as a case study to show the advantages achieved with the proposed approach. Multiple components model the physical dynamics, the communication network and protocol, as well as different control software and external environmental situations. The model of the platooning system is used to compare the performance of Vehicle-to-Vehicle communication against a centralized multi-access edge computing paradigm. Moreover, exploiting the detailed model of vehicle dynamics, different road surface conditions are considered to evaluate the performance of the platooning system. Finally, taking advantage of the co-simulation approach, a solution to drive a platoon in critical road conditions has been proposed. The paper shows how co-simulation and design space exploration can be used for parameter calibration and the design of countermeasures to unsafe situations