Treatment of knee articular cartilage defects: surgical strategies, results and analysis of factors determining the clinical outcome

Articular cartilage lesions, with their inherent limited healing potential, are hard to treat and remain a challenging problem for orthopedic surgeons. Despite the development of several treatment strategies, the real potential of each procedure in terms of clinical benefit and effects on the joint degeneration processes is not clear. Aim of this PhD project was to evaluate the results, both in terms of clinical and imaging improvement, of new promising procedures developed to address the challenging cartilage pathology. Several studies have been followed in parallel and completed over the 3-year PhD, and are reported in detail in the following pages. In particular, the studies have been focused on the evaluation of the treatment indications of a scaffold based autologous chondrocyte implantation procedure, documenting its results for the classic indication of focal traumatic lesions, as well as its use for the treatment of more challenging patients, older, with degenerative lesions, or even as salvage procedure for more advanced stages of articular degeneration. The second field of study involved the analysis of the results obtained treating lesions of the articular surface with a new biomimetic osteochondral scaffold, which showed promise for the treatment of defects where the entire osteochondral unit is involved. Finally, a new minimally invasive procedure based on the use of growth factors derived from autologous platelets has been explored, showing results and underlining indicatios for the treatment of cartilage lesions and different stages of joint degeneration. These studies shed some light on the potential of the evaluated procedures, underlining good results as well as limits, they give some indications on the most appropriate candidates for their application, and document the current knowledge on cartilage treatment procedures suggesting the limitations that need to be addressed by future studies to improve the management of cartilage lesions.

Development and Implementation of the Plasma Focus Technology for Radiation Therapy Applications

A Plasma Focus device can confine in a small region a plasma generated during the pinch phase. When the plasma is in the pinch condition it creates an environment that produces several kinds of radiations. When the filling gas is nitrogen, a self-collimated backwardly emitted electron beam, slightly spread by the coulomb repulsion, can be considered one of the most interesting outputs. That beam can be converted into X-ray pulses able to transfer energy at an Ultra-High Dose-Rate (UH-DR), up to 1 Gy pulse-1, for clinical applications, research, or industrial purposes. The radiation fields have been studied with the PFMA-3 hosted at the University of Bologna, finding the radiation behavior at different operating conditions and working parameters for a proper tuning of this class of devices in clinical applications. The experimental outcomes have been compared with available analytical formalisms as benchmark and the scaling laws have been proposed. A set of Monte Carlo models have been built with direct and adjoint techniques for an accurate X-ray source characterization and for setting fast and reliable irradiation planning for patients. By coupling deterministic and Monte Carlo codes, a focusing lens for the charged particles has been designed for obtaining a beam suitable for applications as external radiotherapy or intra-operative radiation therapy. The radiobiological effectiveness of the UH PF DR, a FLASH source, has been evaluated by coupling different Monte Carlo codes estimating the overall level of DNA damage at the multi-cellular and tissue levels by considering the spatial variation effects as well as the radiation field characteristics. The numerical results have been correlated to the experimental outcomes. Finally, ambient dose measurements have been performed for tuning the numerical models and obtaining doses for radiation protection purposes. The PFMA-3 technology has been fully characterized toward clinical implementation and installation in a medical facility.

Design and characterization of wideband Hall current sensors in BCD technology for smart power and metering applications

Power electronic circuits are moving towards higher switching frequencies, exploiting the capabilities of novel devices to shrink the dimension of passive components. This trend demands sensors capable enough to operate at such high frequencies. This thesis aims to demonstrate through experimental characterization, the broadband capability of a fully integrated CMOS X-Hall current sensor in current mode interfaced with a transimpedance amplifier (TIA), chip CH09, realized in CMOS technology for power electronics applications such as power converters. The system exploits a common-mode control system to operate the dual supply system, 5-V for the X-Hall probe and 1.2-V for the readout. The developed prototype achieves a maximum acquisition bandwidth of 12 MHz, a power consumption of 11.46 mW, resolution of 39 mArms, a sensitivity of 8 % /T, and a FoM of 569-MHz/A2mW, significantly higher than current state-of-the-art. Further enhancements were proposed to CH09 as a new chip CH100, aiming for accuracy levels prerequisite for a real-time power electronic application. The TIA was optimized for a wider bandwidth of 26.7 MHz with nearly 30% reduction of the integrated input referred noise of 26.69 nArms at the probe-AFE interface in the frequency band of DC-30 MHz, and a 10% improvement in the dynamic range. The expected input range is 5-A. The chip incorporates a dual sensing chain for differential sensing to overcome common mode interferences. A novel offset cancellation technique is proposed that would require switching of polarity of bias currents. Thermal gain drift was improved by a factor of 8 and will be digitally calibrated utilizing a new built-in temperature sensor with a post calibration measurement accuracy greater than 1%. The estimated power consumption of the entire system is 55.6 mW. Both prototypes have been implemented through a 90-nm microelectronic process from STMicroelectronics and occupy a silicon area of 2.4 mm2.

The role of technology at school: new perspectives on distance education and cyberbullying

The integration of digital technology in school is a complex phenomenon that affects both teaching and peer relationships. Accordingly, the main aim of this dissertation was to investigate the implementation of distance education among Italian teachers during the COVID-19 pandemic and analyze peer relationships concerning cyberbullying and bullying. While the theoretical section provided an overview of the phenomena, four empirical studies were presented. The first one tested a moderated moderation model among 178 secondary teachers on the interactions among perceived usefulness, perceived ease of use of technology and online teaching self-efficacy. Findings showed that each variable significantly predicted the intention to use technology. In addition, a moderation effect of online teaching self-efficacy on perceived usefulness was found. The second study analyzed the differences in factors promoting the integration of digital technology among 357 teachers of different levels and subjects and their positive and negative experiences with distance education. Results revealed several differences in the function of the grade and subjects taught. Moreover, four main themes emerged from the content analysis. The third study investigated the dyadic perception of bullying and cyberbullying among 50 students using the eye-tracker. Findings showed that, despite differences among different kinds of bullying and cyberbullying, the victim and bully were the most observed roles. Finally, the last study tested two multiple mediation models among 563 students on the association between bullying, cyberbullying, and well-being, considering three different variables related to the school context (peer network, teacher support and school connectedness). The results highlighted the importance of peer networks and school connectedness in mediating the association between victimization, cybervictimzation and well-being. Taken together, the findings provided a rich overview of digital technology integration in schools, highlighting positive and negative aspects and its implications for future research and school policies.

Distributed argumentation technology: advancing risk analysis and regulatory compliance of distributed ledger technologies for transaction and management of securities

Distributed argumentation technology is a computational approach incorporating argumentation reasoning mechanisms within multi-agent systems. For the formal foundations of distributed argumentation technology, in this thesis we conduct a principle-based analysis of structured argumentation as well as abstract multi-agent and abstract bipolar argumentation. The results of the principle-based approach of these theories provide an overview and guideline for further applications of the theories. Moreover, in this thesis we explore distributed argumentation technology using distributed ledgers. We envision an Intelligent Human-input-based Blockchain Oracle (IHiBO), an artificial intelligence tool for storing argumentation reasoning. We propose a decentralized and secure architecture for conducting decision-making, addressing key concerns of trust, transparency, and immutability. We model fund management with agent argumentation in IHiBO and analyze its compliance with European fund management legal frameworks. We illustrate how bipolar argumentation balances pros and cons in legal reasoning in a legal divorce case, and how the strength of arguments in natural language can be represented in structured arguments. Finally, we discuss how distributed argumentation technology can be used to advance risk management, regulatory compliance of distributed ledgers for financial securities, and dialogue techniques.