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Tunisia’s migration politics and the stabilisation of authoritarian regime: financial resources, legitimation, and repression in the context of European border externalisation
No full textThis dissertation examines how migration politics have contributed to the stabilisation of Tunisia’s authoritarian regime under President Kaïs Saïed in the context of intensified European border externalisation. It argues that irregular migration governance—far from being a neutral policy domain—has become a strategic tool for regime consolidation, operating through three interrelated pillars: financial resources, legitimation, and repression. Drawing on and adapting Gerschewski’s framework of authoritarian stability, the study replaces the classical pillar of co-optation with financial resources, highlighting the centrality of European migration-linked funding in reinforcing Tunisia’s security apparatus and political autonomy. The thesis is structured around three core articles. The first traces the evolution of Tunisia’s migration diplomacy and shows how the regime strategically leverages migration cooperation with the EU to extract financial and political support, while presenting Tunisia as both a stabilising partner and a victim of foreign interference. The second article explores the politicisation of immigration in domestic discourse, revealing how migration has been framed through conspiracy theories and anti-interference narratives to construct regime legitimacy and redefine national identity. The third article investigates how migration governance has enabled increased repression against both Sub-Saharan migrants and civil society actors, arguing that migration-related repression is not a byproduct but a key mechanism of authoritarian entrenchment. Methodologically, the dissertation is grounded in 18 months of fieldwork in Tunisia, including 29 interviews and extensive primary document analysis. It contributes to debates on migration diplomacy, authoritarian resilience, and EU externalisation policies by illustrating how migration politics and political regimes are co-constitutive. In doing so, it challenges static distinctions between democracy and autocracy, showing how transnational migration governance shapes and is shaped by authoritarian statecraft in contemporary Tunisia
Anti-doping analysis in sport: new methods on biological samples to protect athlete health and safety
No full textIn this PhD project, original and innovative approaches for the qualitative-quantitative analysis of doping substances have been studied, developed and validated for applications in various fields such as forensic, clinical and pharmaceutical. All parameters involved in the developed analytical workflows have been adequately and accurately optimized, from sample collection to sample pretreatment to instrumental analysis. Advanced dry blood microsampling technologies have been developed, which can bring several advantages to the method as a whole, such as a significant reduction in the use of solvents, feasible storage and transport conditions and improvement of the stability of the analyte. At the same time, the use of capillary blood allows to increase the compliance of the subject and the applicability of the global method by exploiting such innovative technologies. The biological samples involved in this project were subjected to optimized pretreatment techniques developed ad hoc for each target analyte, also making use of advanced microextraction techniques. Finally, original and advanced instrumental analytical methods based on high-performance liquid chromatography and nano liquid chromatography (HPLC, Nano UHPLC) coupled to mass spectrometry were developed. In addition, a pharmacovigilance study coupled with statistical analysis was carried out to assess the health risk of certain specific doping substances. Each method has been designed to achieve highly selective, sensitive but sustainable systems and has been validated according to international guidelines. All methods developed here have proven to be suitable for the analysis of test compounds and may be useful tools in pharmaceutical chemistry, pharmaceutical analysis, clinical studies and forensic investigations
Virtual surgical planning and patient-specific design driven by emerging technologies
Get PDFIn recent years, the integration of emerging technologies in surgery has facilitated the development of innovative approaches to improve preoperative planning and surgical performance. This dissertation provides a comprehensive investigation into the application of emerging engineering technologies – such as computer-aided design, 3D printing, and extended reality – to develop patient-specific models and instruments, addressing the increasing demand for precision and personalization in surgical treatment. The methodology involved the development of a structured workflow that combines engineering and medical expertise, integrating advanced imaging technologies – including computed tomography and magnetic resonance imaging – with 3D segmentation and 3D modeling software. Furthermore, the study explored additive manufacturing technologies, including fused deposition modeling, stereolithography, and laser powder bed sintering, as well as a range of 3D printing materials. These ranged from basic polymers, such as polylactic acid and thermoplastic polyurethane, to more advanced materials like polyether-ether-ketone and titanium alloy. The findings of this research have been successfully translated into clinical scenarios, enabling continuous refinement of both the workflow and surgical techniques to achieve increasingly patient-specific and innovative design. The results highlight the effectiveness of technology integration in surgical planning, demonstrating a significant reduction in operative time and intraoperative fluoroscopy exposure. The use of custom-made instruments has proven to be reliable and safe, offering economic and operational advantages. In addition, experimental research has led to promising developments, such as the design of lattice structures for bone grafts and implants with improved osseointegration properties. Looking beyond the present, this research underscores the growing trend towards novel paradigms, including the establishment of in-hospital 3D laboratories for virtual surgical planning and the point-of-care fabrication of patient-specific devices. These advancements are poised to drive a transformative evolution in surgical care, fostering a new era of precision medicine and personalized treatment strategies
Exploring elderly multimorbid heart failure patients' health-related quality of life within a blended collaborative care framework: understanding the role of care managers
Get PDFIntroduction: Health-Related Quality of Life (HRQoL) is considered a primary outcome in person-centered treatments for heart failure (HF) multimorbid elderly patients. Understanding the factors influencing HRQoL and the role of care managers (CMs) in personalized care is essential.
Aims: Study 1: explore sociodemographic, clinical, psychological and psychosocial characteristics on HRQoL among elderly multimorbid HF patients; Study 2: explore CMs’ perspectives on their role within a Blended Collaborative Care (BCC).
Methods: Study 1 analyzed data from HF patients (65+ years, ≥2 comorbidities, psychological distress) in the ESCAPE BCC trial (Horizon 2020, Grant 945377). Data included sociodemographics, medical history, and standardized psychological assessments.
Study 2 collected qualitative data through semi-structured interviews with CMs (Italy: N=4; Denmark: N=2), analyzed using thematic coding.
Results: Study 1 included 33 patients (mean age: 77.6 ± 6.8 years; 52% male). NYHA class was negatively associated with better disease-specific QoL. Higher perceived health status was linked to ≤5 years of cardiac disease duration, while more comorbidities and pacemakers correlated with poorer perceived health. Disease-specific QoL was associated with communication tools and anxiety. All QoL types were linked to physical capability. Perceived health differed by frailty, illness perception, and depression, while frailty and depression affected all QoL types. Global QoL varied by physical function and cognitive impairment, and psychological distress was associated only with disease-specific QoL.
Study 2 found that CMs view their role as essential in elderly HF care, emphasizing trust-building and proactive support. However, BCC and the CM role require adaptation to clinical practice.
Conclusions: The research provided a better understanding of HRQoL determinants in older multimorbid HF patients. In addition to clinical characteristics, factors such as communication tools, physical and cognitive status, frailty, illness perception, and psychological distress should be recognized in patients’ care. BCC is suggested to be better adapted to clinical practice
Bologna Healing Stifle Injury Index in monitoring the healing process of dogs treated with “Tibial Plateau Levelling Osteotomy” for cranial cruciate ligament rupture and comparison of osteoarthritis progression between osteotomy techniques
Get PDFLa rottura del legamento crociato craniale è una patologia comune che interessa l’articolazione del ginocchio del cane. Il Bologna Healing Stifle Injury Index (BHSII) è un questionario realizzato e validato presso il Dipartimento di Scienze Mediche Veterinarie di Bologna nel 2019 allo scopo di valutare il processo di guarigione dell’articolazione del ginocchio a seguito del trattamento chirurgico per la rottura del legamento crociato nel cane. Tale strumento possiede sia una sezione relativa alla valutazione clinica compilata dal Medico veterinario, sia una sezione relativa alla percezione della qualità di vita del paziente rivolta al proprietario. L’obiettivo principale di questo progetto è stato quello di approfondire la valutazione del processo di guarigione durante i 6 mesi successivi al trattamento chirurgico, ponendo l’attenzione su una tecnica osteotomica, la “Tibial Plateau Leveling Osteotomy” (TPLO), utilizzando il BHSII. I risultati ottenuti hanno evidenziato un miglioramento statisticamente significativo nei 6 mesi postoperatori, ma si sono evidenziate differenze interspecifiche tra i differenti aspetti valutati che sono state approfondite e discusse. Inoltre, è stato valutato il grado di osteoartrosi dell’articolazione del ginocchio nei 6 mesi post operatoti, attribuendo un punteggio da 0 a 3 in 14 localizzazioni radiografiche. In ultimo, è stato eseguito un confronto tra la progressione della degenerazione articolare di pazienti sottoposti a TPLO e pazienti sottoposti a “Tibial Tuberosity Advancement” (TTA). La progressione dell’osteoartrosi permane anche a seguito di trattamento, ma si esplica in modo differente nelle diverse localizzazioni radiografiche, coerentemente con le proprietà biomeccaniche ottenute dalle due tecniche chirurgiche descritte. Nonostante non si identifichi una tecnica migliore per il trattamento del legamento crociato nel cane, questi dati ampliano ulteriormente la valutazione del processo di osteoartrosi che ne deriva, e pone le basi per nuovi studi con un maggior numero di casi e nel confronto di altre tecniche intracapsulari ed extracapsulari.Cranial cruciate ligament rupture is a common stifle joint disease in dogs. The Bologna Healing Stifle Injury Index (BHSII) is a questionnaire created and validated at the Department of Veterinary Medical Sciences in Bologna in 2019 in order to assess the healing process of the stifle joint following surgical treatment for cruciate ligament rupture in dogs. This instrument has both a section on the clinical evaluation completed by the clinician and a section on the perception of the patient's quality of life addressed to the owner. The main objective of this project was to evaluate the 6 months healing process after an osteotomy technique, the ‘Tibial Plateau Leveling Osteotomy’ (TPLO), using the BHSII. The results obtained showed a statistically significant improvement in the 6 months postoperatively, but highlighted interspecific differences that were discussed in detail. In addition, the degree of osteoarthritis of the stifle joint in the 6 months post-operatively was assessed by scoring from 0 to 3 in 14 radiographic locations. Finally, a comparison was made between the progression of joint degeneration of patients undergoing TPLO and patients undergoing Tibial Tuberosity Advancement (TTA). The progression of osteoarthrosis persists even after treatment, but occurs differently in the 14 radiographic locations, accordingly to the biomechanical properties obtained from the two surgical techniques described. Although no best technique is identified for cruciate ligament treatment in the dog, these data further extend the evaluation of the osteoarthrosis stifle joint process. Further studies are necessary in order to compare other techniques used for cranial cruciate ligament rupture treatment
Characterising fractured crystalline basement evolution through time, Smøla island, Mid-Norway: an integrated approach combining deterministic datasets for stochastic applications
Get PDFGeologically old crystalline basement rock volumes, such as Smøla island in the mid-Norwegian passive margin, possess complex natural fracture and fault arrays which have formed through polyphase deformation histories. Deconvoluting these fracture networks into discrete formation events is challenging owing to the typical lack of absolute time constraints, which also limits understanding of past petrophysical properties during network evolution. Addressing these challenges, this thesis utilises a two-part temporally constrained study. The first part comprises a deterministic characterisation of Smøla, with the second part focussing on stochastic modelling and reconstruction. By utilising lineament analysis, field mapping, drill hole logging, 3D modelling, petrographic and microstructural studies, and fault gouge K–Ar geochronology, five deformation episodes (D1 to D5) were interpreted with associated synkinematic mineralisation, geometrical, and kinematic trends. D1 (after ~395 Ma) involved epidote–prehnite veins produced from brittle transtension along the regional Møre Trøndelag Fault Complex. D2 (comprising two stages, ~300 Ma and ~200 Ma) involved sericite–chlorite–calcite mineralised structures related to strike–slip faulting. D3 (~128–100 Ma) involved the formation of chlorite–hematite fractures associated with pervasive dip–slip, possibly transpressional, faulting. The later episodes, D4 (after ~75 Ma) and D5 (assumed Cretaceous–Paleogene), produced hematite–zeolite–calcite and quartz–calcite veins resulting from regional crustal extension. The second part then incorporated the deterministic statistical descriptions of the deformation features on Smøla to reconstruct the D4+5 to D1 networks via a stochastic ‘grown’ DFN modelling approach, using progressive fracture back–stripping, from <70–60 Ma to 395 Ma. 3D permeability tensors and 2D connectivity maps extracted from the models revealed the evolution of permeability anisotropy and connectivity during the prolonged fracture saturation of the rock mass. These results correspond to the timing of hydrocarbon migration activity offshore Norway. This conceptual approach establishes a framework to resolve reservoir charging histories of fractured crystalline basement volumes
Artificial canals restoration through nature-based solutions: experience in Po Plain with a vegetation and water quality view point
Get PDFFloodplains provide crucial ecological and social benefits. Their fertile soils and proximity to water have historically attracted human settlement while simultaneously offering ecosystem services to wider catchments. Yet, the expansion of levees, dams, and engineered canals for urban and agricultural development has increasingly threatened these functions. The Po Plain, one of Europe’s largest alluvial plains shaped by the Po River and its tributaries, exemplifies this tension. Over the last century, land reclamation, intensive farming, and urbanization have profoundly altered its natural hydrological dynamics. Artificial canals, though essential for irrigation and drainage, have caused reductions in riparian vegetation diversity and promoted nutrient accumulation in water and sediments. This dissertation investigated the use of nature-based solutions, specifically pond construction and canal bank reshaping, as strategies to restore ecological quality. A five-year monitoring program was carried out in the Emilia-Romagna region (Italy), focusing on water, sediment, and vegetation indicators. Results indicated that neither water nor sediment presented risks for agriculture or surrounding habitats. Nevertheless, the interventions produced negligible short-term improvements in water and sediment quality, an outcome attributed both to the limited spatial extent of the measures and to major floods in 2023, which temporarily degraded conditions. In contrast, vegetation responded more positively: biodiversity increased despite reductions in total cover caused by flooding and the interventions themselves. This highlights the sensitivity of riparian plant communities and the potential for targeted management to restore ecological value. The study concludes that nature-based solutions can contribute to the enhancement of agricultural floodplains, although significant, measurable changes require larger-scale applications and longer monitoring horizons
The Integrator-PP2A complex at the crossroads of development and cancer
Get PDFTranscriptional regulation relies on the Integrator complex and Protein Phosphatase 2A (PP2A), forming the Integrator–PP2A complex (INTAC). INTAC plays a pivotal role in RNA Polymerase II (RNAPII) pause-release, which regulates gene expression. Dysregulation of this system can have profound biological consequences. This thesis explores the PP2A-Integrator axis in two contexts: neurodevelopmental disorders linked to the R182W mutation in PPP2R1A, a core PP2A subunit, and prostate cancer progression involving loss of Integrator Subunit 6 (INTS6), a key INTAC component. In the first study, Induced Pluripotent Stem Cells (iPSCs) were used to model the PPP2R1A R182W mutation. The mutation caused morphological defects and impaired neural network formation. Transcriptomic and genomic analyses revealed dysregulation of neurogenesis-related genes and altered RNAPII binding. Mass spectrometry indicated disrupted interactions between PP2A and the Integrator complex, implicating defective PP2A-Integrator interactions in neurodevelopmental disorder pathogenesis. The second study focused on INTS6 in prostate cancer. Surprisingly, CRISPR/Cas9 knockout of INTS6 in DU145 cells reduced proliferation and tumor growth in vitro and in vivo, contrary to its tumor-suppressive role. Gene expression profiling showed disrupted pathways in cell cycle progression and differentiation. Analysis of DDX26B, an INTS6 homolog, revealed alternative splicing of exon 11 impacts its interaction with the Integrator complex and its ability to compensate for INTS6 loss. These findings underscore the critical role of PP2A-Integrator interactions in transcriptional regulation. Disrupting this axis—via PPP2R1A mutations or INTS6 loss—leads to significant gene expression changes, affecting differentiation and proliferation. The PP2A-Integrator complex emerges as a vital regulatory mechanism in both neurodevelopmental disorders and cancer
Development of perinatal cell spheroids with dual potential for type 1 diabetes therapy: insulin production and immune modulation
Get PDFType 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by the immune system's destruction of pancreatic beta-cells, leading to insulin deficiency. Conventional treatments focus on insulin replacement, which does not address the underlying immune attack against beta-cells. Therefore, considerable research has been directed towards stem cell therapy, specifically taking advantage of three-dimensional (3D) cell cultures for enhancing the immunomodulatory and differentiative capacities of stem cells. The final goal of the study is to develop a cellular therapy for T1DM by using perinatal cells to create spheroids that can release insulin and mitigate autoimmune responses.
The aim of this study is to create a reliable cellular model for regenerative medicine applications in T1DM. Specifically, it aims to develop 3D co-culture spheroids of amniotic epithelial cells (AECs) and Wharton's jelly mesenchymal stromal cells (WJ-MSCs) to restore insulin production and protect insulin producing cells from autoimmune destruction.
We created co-culture spheroids of AECs and WJ-MSCs in a 1:1 ratio. These spheroids were analyzed for viability, extracellular matrix production, and hypoxic state. The immunomodulatory ability was evaluated by co-culturing with activated PBMCs and T cells. AECs were differentiated into insulin-producing cells, confirmed by immunofluorescence for specific markers, and combined with undifferentiated WJ-MSCs, which have strong immunomodulatory properties.
The undifferentiated co-culture spheroids remained stable and viable in long-term culture with consistent extracellular matrix production. Moreover, the perinatal spheroids showed significant immunomodulatory properties, reducing pro-inflammatory cell activation and promoting anti-inflammatory responses. Spheroids with differentiated cells combined with undifferentiated WJ-MSCs successfully formed cohesive structures and showed potential for insulin production.
Perinatal spheroids represent a promising dual approach for developing new T1DM treatment. Their ability to modulate the immune system and differentiate into insulin-producing cells may address both the symptoms and underlying causes of T1DM, offering a comprehensive cellular therapy beyond traditional insulin replacement
Role and regulation mechanisms of glycosyltransferases in cancer: focus on B4GALNT2.
Get PDFThis thesis deals with the significance of glycosyltransferases in cancer. It is comprised of three parts. In the first one was established the correlation between the expression level of 114 glycosyltransferases and prognosis using transcriptomic and clinical data of 21 TCGA cancer cohorts, identifying glycosyltransferases generally associated to good or poor prognosis. The second part aimed to investigate the regulation mechanisms of the glycosyltransferase β1,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) in colorectal cancer (CRC). B4GALNT2 expression is high in normal colon but is strongly inhibited in CRC. However, high B4GALNT2 correlates with good prognosis in Colorectal Adenocarcinoma TCGA cohort. Beside the certain but not exclusive role of the promoter methylation, other mechanisms responsible for B4GALNT2 downregulation in CRC were investigated. Several transcription factors and miRNAs potentially regulating B4GALNT2 were screened in normal and cancer TCGA samples and in CRC cell lines (CCLE), thus identifying FOXD1 and miR-204-5p as promising B4GALNT2 inhibitory factors in CRC. Their transient transfection in the high-B4GALNT2 expresser CRC cell line GP2d significantly reduced B4GALNT2 mRNA and enzyme activity. Promoter activity was assessed by luciferase assay using a genomic region upstream B4GALNT2 translational start codon, putatively containing FOXD1 binding sites. Transfected GP2d cells with or without FOXD1 cotransfection were assayed for luciferase, showing that in presence of FOXD1 cotransfection the progressive deletion of FOXD1 sites altered luciferase transcription. FOXD1 knockdown in SW948 CRC line lacking B4GALNT2 partially restored B4GALNT2. Hence, FOXD1 and miR-204-5p play a major role in B4GALNT2 downregulation in CRC. The third part of the thesis evaluated the impact of forced B4GALNT2 expression on the neoplastic phenotype of two non-CRC gastrointestinal cancer cell lines. Despite previous studies proved that B4GALNT2 stable transfection in CRC cell lines reduced malignancy, the tendency in non-CRC cell lines was the opposite, indicating that its role of malignancy modulator is CRC specific