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Fundamental rights of the taxpayer in the European legal order: the defining traits of a "functionalised" model of protection
Get PDFLa tesi ha per oggetto la disamina dell’attuale stato delle tutele del contribuente nel modello europeo di protezione dei diritti fondamentali. La ricerca si è proposta di adottare una prospettiva sistematica e dialettica, per far emergere i punti di contatto (e contrasto) fra le esigenze “endemiche” dell’ordinamento dell’Unione e la sfera del contribuente. È così emersa la pervasività dell’ottica funzionalista nella struttura più intima del diritto dell’Unione, che ha assunto significativa rilevanza anche per l’oggetto della ricerca, tanto con riferimento agli spazi di applicabilità dei diritti fondamentali europei in ambito tributario, quanto ai criteri che possono legittimarne una limitazione. L’indagine si è, poi, soffermata sul ruolo esplicato dal modello europeo nella “formazione” dei diritti partecipativi del contribuente e, più nello specifico, del cd. “diritto ad essere ascoltato”. Infine, si sono tracciate le ripercussioni derivanti dalla digitalizzazione dell’Amministrazione finanziaria, anche in considerazione dell’utilizzo di strumenti di intelligenza artificiale, emergendo il rischio di un’emarginazione, nel modello europeo, delle prerogative del contribuente in tale ambito, prospettandosi possibili soluzioni per rimediarvi.This dissertation explores the current state of taxpayer protections within the European framework for fundamental rights. Adopting a systematic and dialectical approach, the research highlights points of convergence and tension between the intrinsic needs of the EU legal order and the taxpayer’s sphere. The study reveals the pervasive influence of a functionalist perspective within EU law, which has significant implications for this field — both in defining the scope of fundamental rights in tax matters and in determining the criteria that may justify their limitation.
The analysis then examines the role of the European framework in shaping taxpayers’ participatory rights, with a particular focus on the so-called “right to be heard”. Finally, the study considers the impact of digitalization in tax administration, especially with the increasing use of artificial intelligence. This technological shift raises concerns regarding the potential marginalization of taxpayer rights, prompting a discussion on possible remedies in order to safeguard them
Aorta and endografts geometrical changes after endovascular treatment for thoracoabdominal aortic aneurysms: development of novel predictive indices using 3d anatomical models
Get PDFIntroduzione: Il trattamento mediante endoprotesi fenestrate o ramificate (F/B-EVAR) è una tecnica consolidata. Le complicanze più comuni sono rappresensatate dall’nstabilità dei viscerali target (iTVV) e dalla migrazione del corpo principale. L’obiettivo di questo studio è analizzare i cambiamenti morfologici e geometrici dell’aorta e degli endograft di questi pazienti per identificare indici predittivi di complicanze utilizzando modelli virtuali 3D.
Materiali e Metodi: Sono stati analizzati retrospettivamente tutti i pazienti con TAAA e J/P-AAA sottoposti a F/B-EVAR tra il 2010 e il 2022. Per ogni paziente è stato generato un modello 3D nelle fasi pre-operatoria (PRE), post-operatoria (POST) e di follow-up (FOLLOW-UP). I modelli 3D sono stati analizzati e confrontati. È stato selezionato un gruppo di controllo per ciascun gruppo. Le analisi dei modelli 3D si sono concentrate sui TVV e sul corpo principale. Per i TVV è stato valutato l'angolo tra l'aorta e il vaso viscerale. Per il corpo principale, sono stati valutati la migrazione e la rotazione.
Risultati: Un totale di 346 pazienti tra il 2010 e il 2022. 35 pazienti con iTVV sono stati riscontrati durante il follow-up: 20 con endoleak e 15 con stenosi/occlusione del TVV. I pazienti con stenosi/occlusione del TVV non hanno rivelato indici predittivi di complicanze. Invece, solo 13 pazienti con EL sono risultati idonei per l'analisi: 6 F-EVAR e 7 B-EVAR. L'analisi nei pazienti F-EVAR ha mostrato una tendenza predittiva dell'angolo tra l'aorta e i TVV in tutti i pazienti con iTVV. L'analisi del corpo principale nei pazienti B-EVAR ha rivelato indici predittivi di complicanze in termini di migrazione.
Conclusioni: Il trattamento endovascolare del TAAA con F/B-EVAR è associato a buoni risultati a breve e medio termine. Le principali complicanze durante il follow-up comprendono l’iTVV e la migrazione del corpo principale. Sono stati identificatiIntroduction: Treatment using fenestrated or branched endografts (F/B-EVAR) in patients with thoracoabdominal aortic aneurysms (TAAA) and/or juxta/pararenal aortic aneurysms (J/P-AAA) is an established technique. The most common complication involves target visceral vessel (TVV) and migration of the endograft Main Body. The aim of this study is to analyze the morphological and geometric changes of the aorta and endografts during follow-up of these patients to identify predictive indices of complications using virtual 3D models.
Materials and Methods: All patients with TAAA and J/P-AAA who underwent F/B-EVAR between 2010 and 2022 were retrospectively analyzed. For each patient, a 3D model was generated from DICOM images at preoperative (PRE), postoperative (POST), and FOLLOW-UP stages. The 3D models were analyzed and compared. A control group was selected for each. The 3D model analyses focused on the TVVs and the Main Body. For TVVs, the angle between the aorta and visceral vessel was assessed. For the Main Body, migration (Δ-Barycenter) and rotation were evaluated.
Results: A total of 346 patients between 2010 and 2022. 35 patients experienced TVV-instability during follow-up: 20 with endoleak and 15 with stenosis/occlusion. Analyses of patients with stenosis/occlusion revealed no predictive indices of complications.
Only 13 patients with EL were eligible for analysis: 6 F-EVAR and 7 B-EVAR. TVV analysis in F-EVAR patients demonstrated a predictive trend in the angle between the aorta and TVVs in all patients with TVV instability compared to the control group. Main Body analysis in B-EVAR patients revealed predictive indices of complications in terms of Δ-Barycenter, rotation.
Conclusions: Endovascular treatment of TAAA with F/B-EVAR is associated with satisfactory short- and mid-term outcomes. Major complications emerging during follow-up include TVV-instability and Main Body migration. Distinct conformational and geometric changes of the aorta and Main Body were identified in patients with TVV-instability
Innovations in neurological and musculoskeletal rehabilitation: new frontiers in pain management
Get PDFBackground
This thesis investigates innovative strategies for managing musculoskeletal disorders, chronic pain, and neurological rehabilitation, combining traditional and digital rehabilitation interventions. Through collaborations with international institutions, the research explores tele-rehabilitation and proprioceptive training aimed at improving functional outcomes and reducing chronic pain.
Methods
Clinical trials and cross-sectional studies were conducted, including a randomized controlled trial comparing tele-rehabilitation with conventional therapy for knee osteoarthritis. Outcomes were measured using pain, function, and quality of life scales (NPRS, WOMAC, SF-36). In addition, proprioception and balance were assessed in a cross-sectional study on healthy adults. Multimodal pain management strategies were also evaluated, including cognitive-behavioral therapy, neuromodulation (TENS, tDCS), and pharmacological treatments.
Results
Tele-rehabilitation demonstrated comparable effectiveness to conventional therapy in reducing pain and improving function, with NPRS and WOMAC scores showing significant improvements in both groups (p < 0.001). The proprioception study revealed age-related declines in balance, underscoring the importance of targeted training. Multimodal pain management approaches significantly reduced chronic pain and improved patient adherence to rehabilitation protocols, with neuromodulation techniques (TENS, tDCS) proving particularly effective.
Conclusion
Tele-rehabilitation emerges as a viable and accessible alternative for managing musculoskeletal disorders. Proprioceptive training is essential, especially for older adults or those with neurological impairments. The findings support the integration of traditional, digital, and psychological approaches to create a more comprehensive and personalized rehabilitation and pain management model
Evaluation of the real nutritional value of processed food to improve their effect on health and increase their sustainability
No full textCured meats and dairy products are criticized for their salt content and synthetic additives. This has led to the development of strategies to reduce and replace these ingredients. Since the food matrix and technological processes can affect the bioaccessibility of nutrients, it is necessary to study their release during digestion to determine the real nutritional value of foods. In the first part of this PhD project, the impact on the nutritional quality of the reduction of sodium content and of the replacement of synthetic nitrates/nitrites with a combination of innovative formulations was evaluated in Parmigiano Reggiano Cheese and salami. For this purpose, an in vitro digestion model combined with different analytical techniques was used. The results showed that fatty acids and proteins release increased over time during digestion. At the end of digestion, the innovative formulation/processing did not negatively affect fatty acids release and protein hydrolysis, and led to the formation of bioactive peptides.
The excessive intake of sugars is correlated with metabolic diseases. After the intestinal uptake, their release in the blood stream depends on their metabolic fate within the enterocyte. In the second part of this PhD project, the absorption and metabolism of glucose, fructose and sucrose was evaluated using intestinal cell line. A faster absorption of fructose than glucose was observed, and a different modulation of the synthesis/transport of other metabolites by monosaccharides was shown. Intestinal cells were also used to verify the stability and intestinal uptake of vitamins (A and D3) delivered to cells through two vehicles. It was shown that the presence of lipids protected the vitamin from external factors such as light, heat and oxygen, and improved their bioavailability
Overall, the results obtained in this PhD project confirmed that considering only the chemical composition of foods is not sufficient to determine their nutritional value
Mechanical design and hybrid control strategies for overconstrained cable-driven parallel robots
No full textCable-driven parallel robots offer significant advantages in terms of workspace dimensions and payload capability. They are attractive for many industrial tasks to be performed on a large scale, such as handling and manufacturing, without a substantial increase in costs and mechanical complexity with respect to a small-scale application. However, since cables can only sustain tensile stresses, cable tensions must be kept within positive limits during the end-effector motion. This problem can be managed by overconstraining the end-effector and controlling cable tensions. Tension control is typically achieved by mounting a load sensor on all cables, and using specific control algorithms to avoid cable slackness or breakage while the end-effector is controlled in a desired position. These algorithms require multiple cascade control loops and they can be complex and computationally demanding. To simplify the control of overconstrained cable-driven parallel robots, this Thesis proposes suitable mechanical design and hybrid control strategies. It is shown how a convenient design of the cable guidance system allows kinematic modeling to be simplified,
without introducing geometric approximations. This guidance system employs swiveling pulleys equipped with position and tension sensors and provides a parallelogram arrangement of cables. Furthermore, a hybrid force/position control in the robot joint space is adopted. According to this strategy, a particular set of cables is chosen to be tension-controlled, whereas the other cables are length-controlled. The force-controlled cables are selected based on the computation of a novel index called force-distribution sensitivity to cable-tension errors. This index aims to evaluate the maximum expected cable-tension error in the length-controlled cables if a unit tension error is committed in the force-controlled cables. In practice, the computation of the force-distribution sensitivity allows determining which cables are best to be force-controlled, to ensure the lowest error in the overall force distribution when a hybrid force/position joint-space strategy is used
Exploring intestinal microbiota in pigs: validation and application of a novel non-invasive sampling device
No full textThe study of microbiota's temporal dynamics and individual variability remains challenging. While technological advances have deepened understanding of host-associated microbial communities, progress in non-invasive tools for directly studying small intestine (SI) microbiota has been limited. This Ph.D. research validated a novel non-invasive device, the Capsule for Sampling (CapSa), for collecting gut microbiota samples from pigs. Existing methods for microbiota sampling are invasive and non-repeatable (e.g., ileal cannulation) or non-invasive but imprecise for SI studies (e.g., fecal sampling). CapSa addresses these gaps, enabling accurate, repeatable sampling of SI microbiota. Validation was conducted in postweaning and growing pigs, with a standard operating procedure (SOP) developed for its use. Retrieval was feasible for pigs over 12 kg, as smaller pigs' stomachs impeded recovery. Sampling occurred in the SI's first segment for postweaning pigs and the middle segment for growing pigs, yielding microbiota compositions distinct from the large intestine and feces. CapSa was successfully administered repeatedly throughout pigs’ lifespans, allowing longitudinal microbiota studies without slaughtering. Sampling five times during a pig’s life revealed microbiota evolution under normal conditions and after an ETEC infection, showing persistent impacts detectable at slaughter. These findings demonstrate CapSa's potential for studying SI microbiota and other gut biomarkers in pigs, starting from postweaning age. Although further refinement of the SOP could enhance animal welfare, CapSa represents a significant advancement in non-invasive microbiota research. Its ability to provide precise, longitudinal insights into the gut microbiota establishes it as a valuable tool for advancing our understanding of the SI microbiome and its response to environmental and health-related factors
Analysis of inflammatory, metabolic and nutritional parameters as prognostic factors in locally advanced cervical cancer
Get PDFMultiple predictors have been studied and included in predictive models for locally advanced cervical cancer (LACC) treated with chemoradiation (CRT). Among published predictive models there is often heterogeneity for clinical setting, analyzed outcomes and included predictors, which makes it sometimes difficult to apply the model in the real daily practice. Therefore, there is growing interest in investigating emerging prognostic factors that can provide additional valuable information.
To improve the accuracy of outcome predictions and enable treatment customization based on prognostic profiles, we analyzed a large population of patients treated with CRT for LACC in our institution exploring the impact of several parameters on clinical oncological outcomes. We retrospectively analyzed pre-treatment systemic inflammatory indices, nutritional parameters (focusing on sarcopenic obesity), and metabolic parameters such as maximum standardized uptake value (SUVmax).
This analysis reported conflicting outcomes that currently do not support the routine use of the valuated parameters. However, sarcopenic obesity emerged as a novel and significant predictor of adverse outcomes and we confirmed the importance of pre-treatment hemoglobin assessment and anemia correction.
Advanced statistical methodologies and collaborative efforts are needed to enhance the accuracy of prognostic models. Constructing large databases through cooperative initiatives may provide a robust foundation for the development of reliable predictive models in the future
Mixed molecular-clinical index in diffuse large B cell lymhomas
Get PDFI Linfomi Diffusi a grandi cellule B (DLBCL) rappresentano un’ampia varietà̀ di tumori del sangue e vengono attualmente classificati in base a dati morfologici, immunofenotipici, genetici e prognostici. Il Lymphoma & Leukemia Molecular Profiling Project (LLMPP) ha distinto due profili di espressione genica con cui suddividere la cellula di origine (COO) dei DLBCL (GC, germinal center; ABC, activated B Cell). La distinzione ha implicazioni biologiche, prognostiche e terapeutiche. La combinazione, inoltre, dell’Indice Prognostico Internazionale (IPI) con le alterazioni dei geni MYC, Bcl-2 e Bcl-6 potrebbe identificare un gruppo di pazienti a prognosi particolarmente infausta. La metodica usata per la definizione di questi sottogruppi è stato il gene expression profile (GEP) con l’uso di microarray su RNA derivato da tessuto congelato, non di comune accesso, per cui è stato introdotto un algoritmo binario basato sull’immunoistochimica (IHC) da applicare su tessuto fissato in paraffina-formalina (FFPET). L’algoritmo si dimostra, però, poco concorde, soprattutto negli ABC-DLBCL. Un alto grado di concordanza è stato, invece, riscontrato con la valutazione di 20 geni su FFPET con l’uso della tecnologia Nanostring (metodica gold- standard indicata dalla WHO). La valutazione, però, delle alterazioni di Bcl-2, Bcl-6 e MYC con la COO non è sufficiente a descrivere il rischio molecolare di questi pazienti, suggerendo l’esistenza di ulteriori alterazioni geniche ancora da identificare. In più, l’infiltrazione di cellule effettrici dell’immunità è stata dimostrata essere prognostica. Un’analisi genomica comprensiva delle cellule tumorali, del microambiente tumorale e in particolare degli effettori immunitari, combinato con l’IPI, può contribuire alla creazione di un indice prognostico misto, molecolare e clinico, per identificare un sottogruppo di pazienti, all’interno dei sottotipi COO, con prognosi particolarmente sfavorevole e per un trattamento adattato al rischio molecolare.Diffuse Large B-Cell Lymphomas (DLBCL) are a wide variety of blood cancers currently classified on morphological, immunophenotypic, genetic, and prognostic data. The Lymphoma & Leukemia Molecular Profiling Project (LLMPP) has distinguished two gene expression profiles by identifying the cell of origin (COO) in DLBCL: germinal center (GC) and activated B-cell (ABC). This classification carries significant biological, prognostic, and therapeutic implications. Moreover, combining the International Prognostic Index (IPI) with genetic alterations (such in MYC, Bcl-2 and Bcl-6) may help identify a subgroup of patients with particularly poor prognosis. The standard method used to define the COO is gene expression profiling (GEP), performed through microarray analysis on RNA extracted from frozen tissue - an approach not widely available. Alternatively, a binary algorithm based on immunohistochemistry (IHC) has been developed for use on formalin-fixed paraffin-embedded tissue (FFPET). However, this method has shown poor concordance, especially in ABC-DLBCL. More concordance has been achieved using NanoString technology - based on the assessment of a 20-gene panel on FFPET - a method now considered the gold standard by the WHO. However, Bcl-2, Bcl-6, and MYC alterations in combination with COO is still insufficient to fully describe the molecular risk in these patients, suggesting the presence of additional genetic alterations yet to be identified. Furthermore, the infiltration of immune effector cells has been shown to have prognostic significance. A comprehensive genomic analysis encompassing tumor cells, the tumor microenvironment, and immune effectors, integrated with the IPI, could be used for the development of a mixed molecular-clinical prognostic index. This would allow the identification of a high-risk subgroup within COO subtypes, guiding risk-adapted treatment strategies based on molecular profiling
Multiomics data integration of acute myeloid leukemia cases to identify immunogenic profiles
Get PDFThis study explores molecular mechanisms of 5-Azacytidine response in acute myeloid leukemia (AML) using an integrative multi-omics approach, combining data from whole exome sequencing (WES), RNA sequencing (RNA-seq), and neoantigen profiling. We aimed to characterize genetic mutations, transcriptional responses, and immunogenic profiles within AML patient clusters to identify potential biomarkers for predicting treatment efficacy. Samples were collected from patients before and 48 hours after 5-Azacytidine treatment, allowing for a comparative analysis of mutation and gene expression changes in response to therapy. In WES data, we identified distinct mutational landscapes in two patient clusters. Cluster A showed genetic patterns favoring apoptosis and absence of KIT mutations, indicating a possible predisposition to 5-Azacytidine responsiveness. In contrast, Cluster B displayed alterations in key oncogenes such as KIT, ATM, and GNAS, which may contribute to cellular survival mechanisms and potential therapy resistance. Transcriptomic analysis revealed enriched metabolic and cell survival pathways in Cluster B, suggesting adaptive responses that could undermine the efficacy of 5-Azacytidine as a single agent. By contrast, Cluster A’s transcriptional profile was associated with a more direct apoptotic response, aligning with its mutation profile. Neoantigen analysis further distinguished these clusters, with Cluster B showing a higher neoantigen load, suggesting an immunologically active environment that may enhance immune surveillance. This raises the potential for immunotherapy applications, particularly in Cluster B, where could complement 5-Azacytidine to overcome resistance mechanisms. The integration of WES, RNA-seq, and neoantigen data underscores the heterogeneity within AML and provides insight into stratified therapy. Cluster A, with its apoptotic gene signatures and lower neoantigen burden, may respond more favorably to 5-Azacytidine alone, while Cluster B could benefit from combined targeted and immune therapies to address its adaptive resistance profile. This research highlights the importance of comprehensive molecular profiling in AML and lays the foundation for personalized therapeutic approaches based
Harmonising music information retrieval with semantics: from data integration to multimodality
Get PDFIn the era of big data and machine learning, the fragmentation of musical datasets and lack of standardised representations hinder advancements in Music Information Retrieval (MIR). The multifaceted nature of music complicates both the representation of content - with small, task-specific datasets scattered across various formats, and context (metadata), where there is a lack of consistent terminology. These challenges increase the effort required for data collection and pre-processing, reduce reproducibility, and limit the scalability of MIR models. To address these issues, this thesis proposes a unified semantic model to foster interoperability and advance MIR tasks. A specific instance of this fragmentation can be found in harmonic annotations, where harmony is inconsistently represented across datasets, formats, and notational systems. Taking harmony as a use case, this thesis develops a standardised workflow to harmonise disconnected datasets, enabling the creation of large-scale unified corpora. Building on these harmonised datasets, a key contribution is the exploration of harmonic similarity to reveal connections across diverse tracks, periods, and genres through novel state-of-the-art similarity functions. While integrating symbolic data offers significant advantages, certain limitations persist. Primary challenges include the limited diversity of annotated data, often biased toward a narrow range of musical genres, and the inherent ambiguity and subjectivity in harmonic annotations. Such challenges have led MIR tasks like Audio Chord Estimation (ACE) to hit a "glass ceiling," where neither increasing computational power nor the volume of data has led to improved results. To address these issues, this thesis explores a multimodal approach combining audio and chord annotations. We propose a method for enriching datasets with aligned audio annotations and introduce a new ACE model that embeds music theory concepts like consonance and dissonance. This model aims to mitigate chord vocabulary imbalance and annotation subjectivity, advancing the state-of-the-art in audio-based harmonic analysis