Turning the tide: how public R&D investment shapes European regional development

This paper evaluates the impact of Mission-Oriented Innovation Policies and public R&D investment on regional economic development in Europe by quantifying the responses of GDP, employment and private R&D across 243 NUTS-2 regions from 1980 to 2019. Using linear and non-linear Local Projections methods, we find that public R&D investment generates the largest multiplicative effect and produces a greater impact in lagging regions than in leading ones, underscoring its crucial role in fostering regional convergence and driving technological advancement across European regions. Finally, our findings show that fiscal stimuli are especially effective during periods of deep recession

Il «tono costituzionale» del principio di parità di trattamento tra uomo e donna in ambito lavorativo

Il commento alla pronuncia n. 181/2024 della Corte costituzionale si incentra sulla declaratoria di illegittimità costituzionale, per contrasto con il diritto dell'Unione in tema di divieto di discriminazioni, della normativa interna che distingue(va) secondo il genere, in dotazione organica, i posti da mettere a concorso nella qualifica di Ispettore del Corpo di Polizia penitenziaria, in assenza di una giustificazione obiettiva e proporzionata legata ai requisiti essenziali per lo svolgimento dell’attività lavorativa medesima. La pronuncia in commento offre, altresì, interessanti spunti di riflessione in tema di doppia pregiudizialità aggiungendo un ulteriore tassello al dibattito dottrinale e alla evoluzione giurisprudenziale costruitisi sul punto

Conditions for Achieving Digital Justice. Enhancing Inclusivity and Participation in Governance

Artificial intelligence represents a transformative force destined to re-ontologise all human interaction environments, including the legal space, adapting their internal structure to technological efficiency within a socio-technical system. This paradigm shift also alters the concept of the rule of law because it affects the communicative participation of the subject in decision-making processes. Judicial decision-making also experiences these changes. That is a vital space considered by the ‘Sustainable Development Goals’ as central to promoting peaceful and inclusive societies oriented towards sustainable development within an effective and accountable institutional framework. The chapter aims to problematise and theorise some conditions that could make digital justice sustainable, emphasising human-machine cooperation as a symbiotic procedural interaction capable of methodologically leading judicial decisionmaking in a human-led socio-technical ecosystem in which technical practices serve not only to design but also to understand and use those techniques. In this view, formal conditions of the judgment validity remain decisive

Alcune riflessioni sull’utilizzo del criterio della proporzionalità alla qualità e quantità del lavoro per la determinazione del compenso nel lavoro autonomo

Il compenso del lavoro autonomo costituisce tradizionalmente un aspetto particolarmente delicato e problematico: da un lato la cultura giuridica del lavoro sembra refrattaria ad ogni regolamentazione ete- ronoma nel campo del lavoro non subordinato, anche in ragione del rilievo solo relativo del fattore tempo quale misura dell’adempimento; dall’altro lato, l’indiscusso bisogno di tutela economica che promana dal contesto sociale ha dato luogo a interventi legislativi sul compenso delle lavoratrici e dei lavoratori autonomi, sia ordinisti sia non ordini- sti, molto tardivi ed estremamente frammentati. L'A. si misura con questi aspetti concentrandosi sui criteri della determinazione del corrispettivo, alla luce delle più recenti innovazioni legislative e giurisprudenziali

Relational Water in Virginia Woolf’s The Waves: An Elemental Reading

This essay situates The Waves within the Blue Humanities, illustrating how liquid and gaseous water permeates Woolf’s novel as an inherently relational element. First, I will discuss how the shifting focalisation and the vignettes of the natural world create a blend of prose and poetry. Then, I will examine how the various states of water invite the reader to acknowledge the transitions across human and nonhuman scales. As the essay seeks to demonstrate, «The Waves» can be read as a modernist water story that reflects the uncertainties of the Anthropocene, advocating for a reconnection between humans and the environment

Predittività delle decisioni, intelligenza artificiale simbiotica e diritto tributario

L’interesse del legislatore, a livello europeo e nazionale, si è da tempo concentrato sull’utilizzo dell’intelligenza artificiale e sulla crescente simbiosi tra esseri umani e modelli intelligenti, alla luce delle sfide sociali, economiche, legali ed etiche generate dalla diffusione dei sistemi di “Symbiotic AI”. Pur potendo, in astratto, le intelligenze artificiali simbiotiche e gli algoritmi informatici esplicare un’importante funzione nei procedimenti giurisdizionali, in ambito tributario, sembra del tutto peregrina e remota la possibilità di immaginare un giudice robot, non essendo le macchine intelligenti tuttora in grado di sostituirsi integralmente all’essere umano al fine di pervenire ad una decisione. L’intelligenza artificiale simbiotica avrebbe così una valenza residuale nell’ambito della giurisdizione tributaria, consentendo all’organo giudicante di reperire i supporti argomentativi a sostegno della propria decisione e preservando la funzione del giudice (essere umano) chiamato ad adeguare la norma astratta alle caratteristiche peculiari del caso concreto

First-line immune-based combinations or sunitinib in favorable-risk metastatic renal cell carcinoma: a real-world retrospective comparison from the ARON-1 study

Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria. Materials and methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate. We carried out a survival analysis by a Cox regression model. Results: A total of 524 favorable-risk patients were included in the analysis. After a median follow-up of 37.2 months, the median OS in the overall population was 56.1 months. There was no significant difference in OS between patients receiving sunitinib and those receiving TKI + ICI combinations (p = 0.761). Patients on TKI + ICI had significantly longer PFS compared to patient treated with sunitinib (30.7 vs 22.9 months, p = 0.007). Analysis of OS and PFS based on metastatic site revealed that patients with bone metastases benefited more from ICI plus TKI (56 patients with bone metastases receiving IO + TKI, 38 received pembrolizumab plus axitinib, 15 cabozantinib plus nivolumab and 3 pembrolizumab plus lenvatinib), while sunitinib was more effective for pancreatic and glandular metastases. Additionally, the number of metastatic sites played a role, with TKI plus ICI showing superiority in patients with a single metastatic site. The time from RCC diagnosis to metastatic disease also impacted outcomes, with TKI plus ICI being more effective in patients with a shorter interval (i.e., < 36 months). Conclusions: The choice between upfront combination or monotherapy for metastatic favorable prognosis RCC remains a current issue. While combination therapy offers prolonged PFS, it does not necessarily translate to improve OS compared to sunitinib. This real-world study supports the superiority in terms of PFS of TKI plus ICI vs TKI monotherapy but not in OS. Probable, other clinical factors should be taking into account to make clinical treatment decisions in this setting

CC48 a new CB2R agonist/FAAH inhibitor dual drug blocks gastric cancer progression and overcomes paclitaxel resistance

Gastric cancer (GC) has poor survival in advanced stages, with limited treatment options. Paclitaxel (PTX) is commonly used, but resistance often arises, highlighting the need for targeted therapies. Cannabinoid receptor type 2 (CB2R) is overexpressed in several cancers and its activation has been associated with reduced tumor growth and metastasis. This study evaluated the antitumor activity of selected CB2R agonists with dual activity (CC48 and Fi9) compared to single-target compounds (ASF151), a reference agonist (compound 1), and an antagonist (AM630). The compounds’ cytotoxicity was determined in GC lines, including PTX-resistant cells, with different levels of CB2R expression. Firstly, were ported that the addition of CB2R ligands to PTX significantly reduces the actively proliferating cells (Ki67+) even in chemotherapy-resistant GC cells. Concentrations below the IC50 of all compounds were used to minimise toxicity. Activation of Akt/mTORC1 and MAPK cascades were found to be related to antiproliferative activity, which was found to be independent of CB2R expression in the different cell lines. Surprisingly, both agonist and antagonist compounds inhibited cell growth. The interaction of CC48 and the reference compounds 1 and AM630, with P-glycoprotein (P-gp) could explain their greater effectiveness in overcoming PTX resistance. Furthermore, CC48 was particularly effective among the agonists in inducing the expression of key autophagy proteins and activating the apoptotic pathway via caspase 3/7 (p < 0.05). The combination of CC48 with PTX further amplified this effect in both sensitive and resistant cells (p < 0.01). CC48 significantly reduced GC cells migration and epithelial-mesenchymal transition (EMT) by modulating the vimentin protein (p < 0.05). In an orthotopic mouse model, CC48 inhibits tumor volume (p < 0.01)and also reduces the number of Ki67 + cells (p < 0.05), without cytotoxic effects. Histological analysis revealed widespread necrosis with inflammatory and apoptotic features, including pyknotic nuclei and fibrotic replacement in CC48-treatedtumors. Moreover, CC48 treatment reduced circulating levels of G-CSF, IL-12 (p40), and eotaxin (p < 0.05), suggesting an immunomodulatory role. In conclusion CC48, a novel multi-target ligand (MTDL), activating CB2R and inhibiting Fatty Acid Amide Hydrolase (FAAH), effectively blocks GC progression modulating the immune response and overcoming PTX resistance. © The Author(s) 2025

Structured professional judgment in the new italian forensic treatment model: the validation of the italian version of the DUNDRUM TOOLKIT|Il giudizio professionale strutturato nel nuovo modello trattamentale forense italiano: la validazione della versione italiana del DUNDRUM TOOLKIT

Objective: The purpose was to demonstrate the effectiveness of the DUNDRUM Toolkit in Italy. The research focused on evaluating the disposition of forensic patients in REMS and CRAPs, hypothesizing that the correspondence between standardized assessments and juridical decisions was not that satisfying. Methods: The DUNDRUM Toolkit was translated, after adapting it to national standards and tested in different regions. A total of 192 forensic patients from 9 REMS and several CRAPs in Italy were evaluated, comparing current levels of therapeutic safety with those ones considered as most appropriate. The evaluation used DUNDRUM­1 to determine pre­treatment safety needs. The progress in the treatment and recovery was examined through DUNDRUM­3 and DUNDRUM­4. Inter­rater reliability was assessed by two independent evaluators on a sample of 50 patients. All health professionals involved in the research had been previously trained in the use of the DUNDRUM Toolkit. Results: Results revealed that 3.7% of patients in REMS needed more security, while 38.2% could be placed in less restrictive environments. In CRAPs, 56% of patients required a higher level of security. Conclusions: The study demonstrated the validity and reliability of the Italian version of the DUNDRUM Toolkit and highlighted significant discrepancies between current forensic patient placements and needed levels of safety, suggesting the importance of using professional tools in the forensic practice that allow more accurate assessment of safety needs for each patient

A Systematic Search for MeV–GeV Pulsar Wind Nebulae without Gamma-Ray Detected Pulsars

An increasing number of pulsar wind nebulae (PWNe) are being identified in the TeV band by ground-based Imaging Air Cherenkov Telescopes such that they constitute the dominant source class of Galactic TeV emitters. However, MeV-GeV PWN counterparts are still largely lacking. To date, only a dozen PWNe are identified by the Fermi-Large Area Telescope (LAT) in the MeV-GeV band. Most PWNe are located along the Galactic plane embedded within the prominent, diffuse Galactic gamma-ray emission, which makes these sources difficult to disentangle from the bright diffuse background. We present a systematic search for gamma-ray counterparts to known PWNe in the 300 MeV-2 TeV energy band using the Fermi-LAT. We target the locations of previously identified PWNe that lack detected Fermi-LAT pulsars to minimize associated pulsar contamination. The sample includes six previously identified Fermi PWNe and eight Fermi-LAT sources associated with PWNe. We report the analysis of 58 regions of interest and classify Fermi-LAT detected sources as either a likely PWN or a candidate PWN counterpart based on their morphological and spectral characteristics across the broadband spectrum. There are nine unidentified Fermi-LAT sources that we consider as likely PWN counterparts, which, if confirmed to be PWNe, would greatly increase the PWN population detected by the Fermi-LAT from 12 to 21. The remaining Fermi-LAT detected sources are considered weaker PWN candidates. A second approach in the systematic search for gamma-ray emitting PWNe will involve studying the off-pulse phases of Fermi-LAT detected pulsars for the presence of an obscured PWN and will be reported in a subsequent paper