Immagine e differenza. Boehm, Derrida e l’«episteme iconica»

Il lavoro intende chiarire la nozione di differenza iconica sviluppata dal filosofo e storico dell’arte tedesco Gottfried Boehm (1942*). In un primo momento, la tesi si concentra sulla definizione di differenza iconica e sul contesto all’interno del quale questa ha preso origine. In un secondo momento, l’elaborato esamina le fonti teoriche cui Boehm attinge (quali Hans-Georg Gadamer, Maurice Merleau-Ponty e Max Imdahl), al fine di analizzare le fondamenta filosofiche sulle quali si erige la sua proposta filosofica. Per finire, la nozione di differenza iconica è posta in dialogo con la filosofia di Jacques Derrida, allo scopo di indagare il posizionamento boehmiano rispetto alla fenomenologia e alla decostruzione. Attraverso lo studio rigoroso della tenuta teoretica della proposta boehmiana, la tesi esamina le potenzialità e i limiti del pensiero di Boehm, ponendo gli aspetti problematici rilevati sullo sfondo delle odierne teorie dell’immagine e in particolare della Bildwissenschaft (“scienza dell’immagine”) germanofona.The dissertation aims to clarify the notion of iconic difference developed by the German philosopher and art historian Gottfried Boehm (1942*). At first, the dissertation focuses on the definition of iconic difference and the context within which it originated. Secondly, the dissertation examines the theoretical sources Boehm draws on (such as Hans-Georg Gadamer, Maurice Merleau-Ponty and Max Imdahl), in order to analyse the philosophical foundations on which his theory is built. Finally, we let interact the notion of iconic difference with Jacques Derrida’s philosophy, in order to investigate Boehm’s relationship to phenomenology and deconstruction. Through the rigorous study of the theoretical solidity of Boehm’s proposal, the dissertation examines the potentialities and limits of Boehm’s thought, setting the problematic aspects we detect on the background of contemporary image theories and in particular of the German-speaking Bildwissenschaft (‘science of the image’)

Underground hydrogen storage suitability index: A geological tool for evaluating and ranking storage sites

Underground Hydrogen Storage (UHS) is a promising solution to maximize the use of hydrogen as an energy carrier. This study presents a standardized methodology for assessing UHS quality by introducing the Underground Hydrogen Storage Suitability Index (UHSSI), which integrates three sub-indices: the Caprock Potential Index (CPI), the Reservoir Quality Index (RQI), and the Site Potential Index (SPI). Parameters such as porosity, permeability, lithology, caprock thickness, depth, temperature, and salinity are evaluated and ranked from 0 (unsuitable) to 5 (excellent). The methodology was validated using data from six worldwide sites, including salt caverns and aquifers. Sites like Moss Bluff, Clemens Dome, and Spindletop (USA) scored highly, while Teesside (UK), Lobodice (Czech Republic), and Beynes (France) were classified as unsuitable due to shallow depths and microbial activity. A software tool, the UHSSI Calculator, was developed to automate site evaluations. This approach offers a cost-effective tool for preliminary screening and supports the safer development of UHS

La grande riforma del diritto dell’immigrazione e dell’asilo dell’Unione europea: un’analisi d’insieme nella prospettiva dei rapporti tra ordinamenti

La riforma del 2024 può essere considerata una nuova tappa nel processo di “comunitarizzazione” dei settori dell’immigrazione e dell’asilo: per effetto del nuovo quadro giuridico, lo spazio lasciato alle normative statali risulta considerevolmente ridotto; inoltre, le istituzioni e gli organi dell’Unione non ricoprono più un ruolo essenzialmente regolatorio, ma contribuiscono maggiormente alla gestione del fenomeno delle migrazioni. Il pacchetto legislativo approvato dal Parlamento europeo e dal Consiglio è composto in prevalenza da regolamenti, che sono muniti, in quanto tali, di applicabilità diretta, ma che richiedono l’approvazione di numerose misure uniformi di esecuzione e di atti delegati. La riforma comprende pertanto, già a livello di Unione, più fasi: la prima si è conclusa con l’adozione e la pubblicazione sulla Gazzetta Ufficiale dell’Unione Europea di dieci nuovi atti legislativi; la seconda presuppone l’approvazione di ulteriori misure da parte della Commissione europea e del Consiglio. A queste due fasi, seguirà l’intensa attività normativa e organizzativa che la riforma impone agli Stati membri. L’articolo si propone di presentare il nuovo pacchetto legislativo, mettendone in evidenza alcuni profili selezionati che possono essere considerati i pilastri del nuovo quadro giuridico. L’obiettivo è quello di far emergere una visione d’insieme. Inoltre, l’articolo mira a valutare l’impatto della riforma sugli ordinamenti interni, sotto due diversi profili: il primo è connesso alla scelta di utilizzare i regolamenti come fonte principale della nuova disciplina; il secondo attiene all’ampliamento dell’ambito di applicazione della normativa dettata dall’Unione europea in materia di immigrazione e asilo. The 2024 reform can be considered a new stage in the process of ‘communitarisation’ of the immigration and asylum sectors: as a result of the new legal framework, the room left to State legislation is considerably reduced; moreover, the institutions and bodies of the Union no longer play a mere regulatory role, but contribute more actively to the management of the migration phenomenon. The legislative package approved by the European Parliament and the Council is mainly composed of regulations, which are directly applicable, but require the approval of numerous uniform implementing measures and delegated acts. The reform therefore involves several phases at the level of the Union: the first phase ended with the adoption and publication of ten new legislative acts in the Official Journal of the European Union; the second phase requires the approval of further measures by the European Commission and the Council. These two phases will be followed by the intense regulatory and administrative activity that the reform requires of the Member States. Against this background, the article presents the new legislative package, highlighting some selected aspects that can be considered the pillars of the new legal framework, with the aim to provide a comprehensive overview. In addition, the article intends to assess the impact of the reform on domestic legislation, from two different perspectives: the first refers to the use of regulations as the main source of the new discipline; the second concerns the extension of the scope of application of EU legislation on immigration and asylum

Cellule staminali pluripotenti indotte (iPSCs) come modello per studiare la tossicità delle tiopurine: personalizzazione della terapia in pazienti pediatrici con malattie infiammatorie intestinali

Le tiopurine, usate per le malattie infiammatorie intestinali (IBD), possono portare alla pancreatite indotta da tiopurine (TIP), una reazione dose-indipendente che è più grave nei pazienti pediatrici e il cui meccanismo è sconosciuto. Le cellule staminali pluripotenti indotte (iPSCs) sono utili per studiare la TIP in modo personalizzato e questo studio si propone di elucidare questo effetto avverso usando modelli pancreatici 2D e 3D iPSC-derivati. Dieci pazienti pediatrici con IBD, cinque con TIP e cinque senza, e quattro controlli sani, sono stati arruolati presso l'IRCCS Burlo Garofolo (Trieste, Italia). I saggi MTT effettuati sui modelli pancreatici 2D hanno indicato una citotossicità statisticamente maggiore della tioguanina nelle iPSCs e nelle cellule pancreatiche dei pazienti con TIP rispetto ai no-TIP (p<0,001, ANOVA a due vie). Le concentrazioni statisticamente significative erano 2,5x10-7 M (p<0,001, Bonferroni post-hoc test) e 1,6x10-5 M (p<0,05, Bonferroni post-hoc test), rispettivamente per iPSCs e cellule differenziate. Le cellule pancreatiche TIP erano anche statisticamente più sensibili alla mercaptopurina (p<0,001, ANOVA a due vie). Inoltre, le iPSCs dei pazienti producevano solo tioguanosina monofosfato e la sua forma metilata dopo il trattamento con tioguanina, ma le loro concentrazioni non erano significativamente diverse tra TIP e no-TIP. Non sono state notate differenze significative nell'espressione dei geni HPRT, NUDT15, ITPA e PACSIN2 tra iPSCs TIP e no-TIP. Le iPSCs no-TIP, però, esprimevano livelli statisticamente più alti di TPMT (p<0,05, t-test); questa differenza non è risultata invece significativa nelle cellule differenziate. Non sono emerse differenze nell'espressione del target delle tiopurine Rac1 tra iPSCs TIP e no-TIP; al contrario, Rac1 era statisticamente più espresso nelle cellule pancreatiche TIP (p<0,05, t-test). Dunque, la diversa espressione di TPMT nelle iPSCs potrebbe essere correlata all'insorgenza di TIP in queste cellule, mentre differenze nell'espressione di Rac1 potrebbero essere correlate alla TIP nelle cellule pancreatiche. Sono tuttavia necessari ulteriori studi per chiarire meglio il meccanismo della TIP. Sono stati inoltre ottimizzati due protocolli per la generazione di organoidi pancreatici esocrini da iPSCs. Le real-time PCR hanno mostrato che gli organoidi esprimevano livelli più elevati delle due isoforme dell'amilasi pancreatica (AMY2A e AMY2B) rispetto alle iPSCs. Questa differenza era statisticamente significativa per gli organoidi ottenuti con il protocollo 2 (p<0,05, ANOVA a una via e Tukey post-hoc test). Entrambi gli organoidi esprimevano livelli più alti di CK19 e SOX9, marcatori duttali, rispetto alle iPSCs, anche se non in modo significativo. Inoltre, entrambi gli organoidi esprimevano l’insulina, tipica della controparte endocrina, e l’albumina, indicante contaminazioni epatiche. Insulina e albumina erano più elevate negli organoidi ottenuti con il protocollo 1. L'immunofluorescenza ha inoltre confermato, in entrambi gli organoidi, la presenza di amilasi nel citoplasma e di citocheratina 19 a livello dei dotti. La colorazione con ematossilina ed eosina ha ulteriormente confermato che gli organoidi mantengono le caratteristiche istologiche del pancreas in vivo. Pertanto, finora il protocollo 2 sembra essere più specifico e riproducibile del protocollo 1. Una volta scelto il protocollo migliore, sarà usato per generare organoidi da pazienti TIP, no-TIP e da controlli sani, per studiare la TIP in modo più accurato.Thiopurines, used for inflammatory bowel disease (IBD), can lead to thiopurine-induced pancreatitis (TIP), a dose-independent reaction that could be more serious in pediatric patients and whose mechanism is unknown. Induced pluripotent stem cells (iPSCs) are useful to study TIP in a personalized way, and the present study aims to elucidate this adverse effect by using iPSC-derived 2D and 3D pancreatic models. Ten pediatric patients with IBD, five developing TIP and five without it, and four healthy controls, were enrolled at the IRCCS Burlo Garofolo (Trieste, Italy). MTT assays on 2D pancreatic models indicated a statistically higher cytotoxicity of thioguanine in iPSCs and pancreatic cells from TIP patients compared to no-TIP (p<0.001, two-way ANOVA). The statistically different concentrations were 2.5x10-7 M (p<0.001, Bonferroni post-hoc test) and 1.6x10-5 M (p<0.05, Bonferroni post-hoc test), respectively for iPSCs and differentiated cells. Moreover, TIP pancreatic cells were statistically more sensitive to mercaptopurine (p<0.001, two-way ANOVA). In addition, patients’ iPSCs only produced thioguanosine monophosphate and its methylated form after thioguanine treatment, but their concentrations were not significantly different between TIP and no-TIP patients. No statistically relevant differences in HPRT, NUDT15, ITPA, and PACSIN2 gene expression were noticed between TIP and no-TIP iPSCs. On the other hand, no-TIP iPSCs expressed statistically higher levels of TPMT (p<0.05, t-test), but this difference was not significant in differentiated cells. No differences emerged in the expression of the thiopurine target Rac1 between TIP and no-TIP iPSCs; conversely, Rac1 was statistically higher in TIP pancreatic cells (p<0.05, t-test). Thus, TPMT different expression in iPSCs could be related to TIP onset in these cells, while differences in Rac1 expression might be related to TIP onset in exocrine pancreatic cells. Nonetheless, more studies are needed to better elucidate TIP mechanism. We optimized two protocols for the generation of exocrine pancreatic organoids from iPSCs. Real-time PCR showed that organoids expressed higher levels of the two isoforms of pancreatic amylase (AMY2A and AMY2B) compared to iPSCs. This difference was statistically significant for the organoids obtained with protocol 2 (p<0.05, one-way ANOVA and Tukey post-hoc test). Both the organoids expressed higher levels of CK19 and SOX9, ductal markers, compared to iPSCs, despite not significantly. In addition, both the organoids expressed insulin, typical of the endocrine counterpart, and albumin, indicating hepatic contaminations. Insulin and albumin levels were higher in organoids obtained with protocol 1. Immunofluorescence confirmed, in both the organoids, the presence of amylase in the cell cytoplasm, and cytokeratin 19, near the ducts. Hematoxylin and eosin staining further confirmed that the organoids retain the histological features of the pancreas in vivo. Therefore, so far protocol 2 seems to be more specific and reproducible than protocol 1. After choosing the best protocol, it will be used to generate pancreatic organoids from TIP, no-TIP patients, and healthy controls, to study TIP in a more accurate way

A water-responsive calix[4]resorcinarene system: self-assembly and fluorescence modulation

This study explores how water content modulates the self-assembly and fluorescence behavior of two novel calix[4]resorcinarene macrocycles. These macrocycles transition from large, flattened structures in pure THF to large giant vesicles (500-5000 nm) coexisting with small micelles (3.4-3.5 nm) as the water percentage in THF/water mixtures increases up to 53%. At higher water percentages, the assemblies become smaller, forming unimodal micelles with diameters of approximately 140-160 nm. Fluorescence quenching is observed upon water addition, attributed to nonradiative deactivation. These findings highlight water as a key regulator of the assembly and fluorescence of these calix[4]resorcinarene macrocycles, paving the way for further development of water-responsive calixarene systems

Retrospective cohort study on treatment outcomes of early vs late onset gestational diabetes mellitus

Background: Gestational diabetes mellitus (GDM) affects roughly 14% of pregnancies, its prevalence is increasing, and it is associated with a significant risk of complications for both mother and offspring. A high proportion of women with GDM can be detected early in pregnancy. In Italy, early GDM screening occurs in a selective way, as it is performed only in the presence of important risk factors. It remains to be elucidated not only how and when to diagnose early GDM but especially whether to treat it. This study aimed to compare the characteristics and complications of early vs late GDM as assessed and treated in a real-world setting, according to the Italian guidelines of the Istituto Superiore di Sanità. Methods: We conducted a retrospective cohort study in women with GDM delivering singletons between 2017 and 2021. Results: Women with early GDM had higher BMI and a higher proportion of Middle Eastern or African women. Early GDM was independently associated with the use of insulin (p < 0.001). It required also higher doses of insulin, possibly due to the higher BMI. Early GDM was also independently associated with higher post-prandial (after dinner) glucose levels during the 3° trimester (p = 0.04). Nevertheless, early GDM women achieved glucose targets and put on less weight during gestation. Early GDM was independently associated with preeclampsia (p = 0.05). Otherwise, there were no other differences between early and late GDM in terms of pregnancy complications. After delivery, early GDM was independently associated with abnormal glucose tolerance. Conclusions: Early GDM women exhibited more severe GDM features. However, after achieving recommended glucose and body weight targets, there were no substantial differences between early and late GDM in terms of pregnancy complications apart from preeclampsia. These data support diagnosis and treatment of women with early GDM

Eliciting prior information from clinical trials via calibrated Bayes factor

In the Bayesian framework power prior distributions are increasingly adopted in clinical trials and similar studies to incorporate external and past information, typically to inform the parameter associated with a treatment effect. Their use is particularly effective in scenarios with small sample sizes and where robust prior information is available. A crucial component of this methodology is represented by its weight parameter, which controls the volume of historical information incorporated into the current analysis. Although this parameter can be modeled as either fixed or random, eliciting its prior distribution via a full Bayesian approach remains challenging. In general, this parameter should be carefully selected to accurately reflect the available historical information without dominating the posterior inferential conclusions. A novel simulation-based calibrated Bayes factor procedure is proposed to elicit the prior distribution of the weight parameter, allowing it to be updated according to the strength of the evidence in the data. The goal is to facilitate the integration of historical data when there is agreement with current information and to limit it when discrepancies arise in terms, for instance, of prior-data conflicts. The performance of the proposed method is tested through simulation studies and applied to real data from clinical trials

Clinical features and outcomes in carriers of pathogenic desmoplakin variants

Pathogenic variants in the desmoplakin (DSP) gene are associated with the development of a distinct arrhythmogenic cardiomyopathy phenotype not fully captured by either dilated cardiomyopathy (DCM), non-dilated left ventricular cardiomyopathy (NDLVC), or arrhythmogenic right ventricular cardiomyopathy (ARVC). Prior studies have described baseline DSP cardiomyopathy genetic, inflammatory, and structural characteristics. However, cohort sizes have limited full clinical characterization and identification of clinical and demographic predictors of sustained ventricular arrhythmias (VAs), heart failure (HF) hospitalizations, and transplant/death. In particular, the relevance of acute myocarditis-like episodes for subsequent disease course is largely unknown

Adaptive RBF-FD meshless solution of 3D fluid flow and heat transfer problems

This paper describes an adaptive approach for the solution of 3D steady and incompressible flows with the RBF-FD (Radial Basis Function-Finite Difference) meshless method. This method relies on a set of scattered nodes in the domain instead of a traditional mesh data structure. The lack of connectivity information and the absence of the mesh generation make the RBF-FD method particularly advantageous for the accurate numerical solution of many problems of engineering interest. Furthermore, automatic node generation is possible thanks to many algorithms that recently have been proposed. However, as it happens for mesh-based methods, the accurate solution of partial differential equations usually require proper node distributions with higher node density in specific areas. The approach described in this paper allows the re-generation of the entire node distribution in order to minimize some error indicator by automatically adjusting local node density depending on the domain and physical problem. The main contribution of this work is the introduction of some original error indicators which are used for the aforementioned adaptive node generation and the assessment of their effect on accuracy. Results show good convergence properties and highlight some differences in the behaviour of the different adaptive approaches in the spatial error distribution

Correction: The PREVASC study: Prospective REgistry of Valve disease in Asymptomatic Italian elderly SubjeCts

PREVASC stud