超越宣告性模式和判决主义模式* ———麦考密克对“法律推理和法律理论”的重新思考

This paper offers a diachronic reconstruction of MacCormick’s theory of law and legal argumentation: In particular，two related points will be highlighted in which the difference between the perspective upheld in Legal Reasoning and Legal Theory and the later writings is particularly marked． The ? rst point concerns MacCormick’s gradual break with legal positivism，and more speci? cally the thesis that the implicit pretension to justice of law proves legal positivism false in all its different versions． The second point concerns MacCormick’s acceptance of the one－right－answer thesis and the consequent thinning of the differences between MacCormick’s theory of legal reasoning and that of Ronald Dworkin and of Robert Alexy． The intent，however，is not only to describe this change in MacCormick’s thought，but also to attempt a defence of the original view that we ? nd in Legal Reasoning and Legal Theory

Patrick George Zaki, l'Egitto e noi

Il 7 febbraio 2020 Patrick George Zaki, studente di un master internazionale in studi di genere e diritti umani presso l’Alma Mater Studiorum di Bologna nonché attivista presso la ong Egyptian Initiative for Personal Rights (EIPR), è arrestato all’aeroporto del Cairo, dove era atterrato per una breve vacanza in Egitto, e viene sottoposto a detenzione preventiva su richiesta dei pubblici ministeri del tribunale di Mansoura, sua città natale. L’accusa è di istigazione a proteste e propaganda di terrorismo attraverso la pubblicazione sui social network di notizie false finalizzate a turbare la pace sociale e a rovesciare il regime egiziano. Anche l’ultima udienza per decidere sulla scarcerazione dello studente bolognese, il 28 febbraio scorso, ha dato esito negativo, nonostante l’attesa e le pressioni del mondo occidentale e, in primo luogo, dell’Italia. Il caso Zaki ci interroga più su noi stessi che sull’Egitto. Possiamo ancora dire che la cultura dei diritti umani – per usare l’espressione del filosofo argentino Eduardo Rabossi – sia ancora egemone nel nostro mondo? Rispondere a questa domanda non è semplice. In ogni caso, bisogna partire da una breve presentazione della cultura dei diritti che si è sviluppata nel mondo dopo il secondo dopoguerra

Cooperative role of thrombopoietin and vascular endothelial growth factor-a in the progression of liver cirrhosis to hepatocellular carcinoma

Primary thrombopoietic mediator thrombopoietin (THPO) is mainly produced by the liver; it may act as a growth factor for hepatic progenitors. Principal angiogenesis inducer vascular endothelial growth factor-A (VEGF-A) is critical for the complex vascular network within the liver architecture. As a cross-regulatory loop between THPO and VEGF-A has been demonstrated in the hematopoietic system, the two growth factors were hypothesized to cooperatively contribute to the progression from liver cirrhosis (LC) to hepatocellular carcinoma (HCC). The mRNA and protein expression levels of THPO, VEGF-A, and their receptors were examined, compared, and correlated in paired cancerous and LC tissues from 26 cirrhosis-related HCC patients, using qRT-PCR and immunohistochemistry. THPO and VEGF-A were alternatively silenced by small interfering RNA (siRNA) in human liver cancer cell lines Huh7 and HepG2. THPO and VEGF-A expressions significantly increased in tumor versus LC tissues. HCC and paired LC cells expressed similar levels of THPO receptor (R), whereas vascular endothelial growth factor receptor (VEGFR) -1 and VEGFR-2 levels were higher in HCC than in corresponding LC tissue samples. A significant linear correlation emerged between THPO and VEGF-A transcripts in HCC and, at the protein level, THPO and THPOR were significantly correlated with VEGF-A in tumor tissues. Both HCC and LC expressed similar levels of gene and protein hypoxia inducible factor (HIF)-1α. Positive cross-regulation occurred with the alternative administration of siRNAs targeting THPO and those targeting VEGF-A in hypoxic liver cancer cell lines. These results suggest THPO and VEGF-A might act as interdependently regulated autocrine and/or paracrine systems for cellular growth in HCC. This might be clinically interesting, since new classes of THPOR agonistic/antagonistic drugs may provide novel therapeutic options to correct the frequent hemostatic abnormality seen in HCC patients

A microRNA prognostic signature in patients with diffuse intrinsic pontine gliomas through non-invasive liquid biopsy

Diffuse midline gliomas (DMGs) originate in the thalamus, brainstem, cerebellum and spine. This entity includes tumors that infiltrate the pons, called diffuse intrinsic pontine gliomas (DIPGs), with a rapid onset and devastating neurological symptoms. Since surgical removal in DIPGs is not feasible, the purpose of this study was to profile circulating miRNA expression in DIPG patients in an effort to identify a non-invasive prognostic signature with clinical impact. Using a high-throughput platform, miRNA expression was profiled in serum samples collected at the time of MRI diagnosis and prior to radiation and/or systemic therapy from 47 patients enrolled in clinical studies, combining nimotuzumab and vinorelbine with concomitant radiation. With progression-free survival as the primary endpoint, a semi-supervised learning approach was used to identify a signature that was also tested taking overall survival as the clinical endpoint. A signature comprising 13 circulating miRNAs was identified in the training set (n = 23) as being able to stratify patients by risk of disease progression (log-rank p = 0.00014; HR = 7.99, 95% CI 2.38–26.87). When challenged in a separate validation set (n = 24), it confirmed its ability to predict progression (log-rank p = 0.00026; HR = 5.51, 95% CI 2.03–14.9). The value of our signature was also confirmed when overall survival was considered (log-rank p = 0.0021, HR = 4.12, 95% CI 1.57–10.8). We have identified and validated a prognostic marker based on the expression of 13 circulating miRNAs that can shed light on a patient’s risk of progression. This is the first demonstration of the usefulness of nucleic acids circulating in the blood as powerful, easy-to-assay molecular markers of disease status in DIPG. This study provides Class II evidence that a signature based on 13 circulating miRNAs is associated with the risk of disease progression

Genome-wide analyses of platinum-induced ototoxicity in childhood cancer patients: Results of GO-CAT and United Kingdom MAGIC consortia

: Hearing loss (ototoxicity) is a major adverse effect of cisplatin and carboplatin chemotherapy. The aim of this study is to identify novel genetic variants that play a role in platinum-induced ototoxicity. Therefore, a genome-wide association study was performed in the Genetics of Childhood Cancer Treatment (GO-CAT) cohort (n = 261) and the United Kingdom Molecular Genetics of Adverse Drug Reactions in Children Study (United Kingdom MAGIC) cohort (n = 248). Results of both cohorts were combined in a meta-analysis. In primary analysis, patients with SIOP Boston Ototoxicity Scale grade ≥1 were considered cases, and patients with grade 0 were controls. Variants with a p-value <10-5 were replicated in previously published data by the PanCareLIFE cohort (n = 390). No genome-wide significant associations were found, but variants in TSPAN5, RBBP4P5, AC010090.1 and RNU6-38P were suggestively associated with platinum-induced ototoxicity. The lowest p-value was found for rs7671702 in TSPAN5 (odds ratio 2.0 (95% confidence interval 1.5-2.7), p-value 5.0 × 10-7). None of the associations were significant in the replication cohort, although the effect directions were consistent among all cohorts. Validation and functional understanding of these genetic variants could lead to more insights in the development of platinum-induced ototoxicity

Il costituzionalismo contemporaneo ai tempi del Covid-19

L’indeterminatezza è una delle caratteristiche salienti del diritto negli stati costituzionali contemporanei. Tale caratteristica mette in crisi le concezioni “oggettualistiche” del diritto che riducono il diritto a un insieme di norme o a un insieme di fatti e corrobora quelle concezioni che considerano il diritto una pratica sociale interpretativa. La costituzionalizzazione degli ordinamenti giuridici accresce la flessibilità del diritto a detrimento della certezza e impone a tutti – legislatori, giudici e individui soggetti al diritto – di assumersi le proprie responsabilità e i rischi che ne conseguono. Il modo in cui il legislatore, a diversi livelli, fronteggia l’attuale pandemia da Covid-19 costituisce un interessante angolo visuale per riflettere sugli effetti – alcuni positivi, altri negativi – prodotti dall’indeterminatezza del diritto contemporaneo.Indeterminacy is one of the main characteristics of the law in contemporary constitutional States. It challenges the objectualist conceptions of law reduce reduce law to a system of norms or a set of facts and confirms those conceptions that regard the law as an interpretative social practice. Legal systems’ constitutionalization increases legal flexibility at the expense of legal certainty; it imposes to legislators, judges and individuals the responsibility and the associated risks of individuating the law. The ways in which the legislator, at different levels, faces the Covid-19 current pandemic offer an interesting perspective to analyze the positive and negative effects produced by the indeterminacy of contemporary law