Tamoxifen in treatment of hepatocellular carcinoma: a randomised controlled trial

Background Results from small randomised trials on tamoxifen in the treatment of hepatocellular carcinoma (HCC) are conflicting, We studied whether the addition of tamoxifen to best supportive care prolongs survival of patients with HCC. Methods Patients with any stage of HCC were eligible, irrespective of locoregional treatment. Randomisation was centralised, with a minimisation procedure accounting for centre, evidence of disease, and time from diagnosis. Patients were randomly allocated best supportive care alone or in addition to tamoxifen, Tamoxifen was given orally, 40 mg per day, from randomisation until death. Results 496 patients from 30 institutions were randomly allocated treatment from January, 1995, to January, 1997. Information was available for 477 patients. By Sept 15, 1997, 119 (50%) of 240 and 130 (55%) of 237 patients had died in the control and tamoxifen arms, respectively. Median survival was 16 months and 15 months (p=0.54), respectively, No differences were found within subgroups defined by prognostic variables. Relative hazard of death for patients receiving tamoxifen was 1.07 (95% CI 0.83-1.39). Interpretation Our findings show that tamoxifen is not effective in prolonging survival of patients with HCC

Giustizia e letteratura II

The book explores and links different cultures, disciplines and perspectives, with a far more original and broad approach to the relations between “Justice” and “Literature” than more traditional works focused on “Law” and “Literature”. The many contributions from writers, literature and movie critics, psychologists, and criminal law practitioners and scholars, draw a complex and interdisciplinary path through primary texts of Italian and international literature, with the aim of prompting readers’ reflections about core issues related to law, crime, and responsibility. Through the analysis of masterpieces of literature, theatre and cinema, this book aims at stimulating dialogue and debate, as well as critical abilities and a deep-rooted sense of justice, amongst both law professionals and citizens at large. Literature and other forms of narration are presented here as a privileged key to approach long-standing questions about (amongst other) causes and consequences of crime; victimization and coping mechanisms; the role of criminal law and criminal proceedings; legalism and equity; law and ethics; the ‘time’ of justice; freedom, responsibility, culpability and forgiveness; rules, legality, socialization and culture; language and images as mediums for justice issues; the impact of prejudice and of existing balances of power on the application of the law; social and legal mechanisms of exclusion and inclusion; gender issues and legal systems; and so on. A whole section (Part V) is devoted to crimes against humanity and how the literary testimony may be understood both as a strategy to resist injustice and to seek justice, and as a way to prevent further horrors. Through this quest for justice in literature and arts, the volume proposes a wider cultural and research project which defies traditional formalistic and retributive approaches to criminal law, in order to open new perspectives for restorative and reintegrative strategies

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Esigenze di sicurezza nazionale e tutela dei diritti dell'uomo nella recente prassi europea

(Relazione svolta all'Ottavo Convegno della Societ� Italiana di Diritto Internazionale, Verona, 27 giugno 2003

L'interazione fra ordinamenti nella giurisprudenza delle corti internazionali e delle corti supreme europee: i tribunali penali internazionali

Il seminario si è incentrato, in particolare, sulla giurisprudenza rilevante del Tribunale penale internazionale per la ex-Iugoslavia. In presenza di una limitata quantità di norme sostanziali applicabili, il Tribunale si è spesso trovato nella necessità di riempire lacune tramite la creazione di principi o norme. Ciò è quanto si è verificato, ad esempio, nel caso dell'attribuzione di dignità di "jus cogens" al divieto di tortura, ma anche in sede di affermazione di principi garantistici per l'imputato del processo penale internazionale. In tutte queste ipotesi si è fatto costantemente riferimento a norme o principi di altri ordinamenti, a prescindere dall'idoneità di questi ultimi a vincolare, sul piano formale, il giudice internazionale

La questione dell'immunità degli Stati esteri dalla giurisdizione in caso di violazione “grave” di obblighi fondamentali a protezione di diritti individuali

Nell'intervento è stato preliminarmente affrontato il problema della qualificazione degli atti posti in essere dagli Stati con particolare riferimento all'impostazione accolta nella Convenzione delle Nazioni Unite sulle immunità giurisdizionali degli Stati e dei loro beni del 2004, secondo cui il riconoscimento dell'immunità costituisce la regola, mentre la possibilità di convenire in giudizio uno Stato straniero può essere ammessa soltanto in alcune ipotesi tassative, da interpretarsi restrittivamente. Sono state poi analizzate alcune delle disposizioni più rilevanti della Convenzione del 2004, evidenziando le soluzioni che paiono discostarsi maggiormente dalla prassi precedente ed interrogandosi sull'impatto che la nuova Convenzione potrà avere su quegli ordinamenti interni che già prevedono una normativa specifica in materia di immunità degli Stati

L'interazione fra ordinamenti nella giurisprudenza delle corti internazionali e delle corti supreme europee: la Corte di giustizia delle Comunità europee.

Il seminario si è incentrato sulla giurisprudenza della Corte di giustizia delle Comunità europee in tema di rapporti fra ordinamenti, con particolare riferimento: a) alla presa in considerazione dei valori costituzionali degli ordinamenti degli Stati parti; b) alla "comunitarizzazione" di tali valori; c) al rapporto fra ordinamento comunitario e Convenzione europea dei diritti dell'uomo. Un'enfasi particolare è stata posta sull'importanza assunta in materia dal dialogo fra le Corti

Les techniques de protection internationale des droits de l'homme

L'intervention est visée à donner des indications de caractère général sur l'évolution de trois techniques internationales de protection des droits de l'homme :a) en ce qui concerne la technique traditionnelle de la "subsidiarité", on peut observer que cette technique, bien que caractérisante le fonctionnement des principaux systèmes internationaux de protection des droits de l'homme conventionnellement établis, ne se situe plus dans un cadre de séparation nette entre les systèmes internationaux et les mécanismes nationaux de protection, mais plutôt dans un cadre d'intégration croissante entre mécanismes nationaux et internationaux de protection; b) à l'égard de la nature « objective » ou « erga omnes » des obligations en matière des droits de l'homme, que le rôle joué "ex se" par cet aspect, dans le cadre des techniques de protection des droits de l'homme, est, de plus en plus, reduit, lorsque l'objectivisation de ces systèmes de contrôle est, de plus en plus, le produit de la consolidation des fonctions d' "orientation générale" de ces systemès, principalement dans le cadre européen, mais aussi dans d'autres systèmes régionaux et –bien que dans une moindre mesure – dans le cadre universel;c) l'accroissement du caractère « judiciaire » des systèmes de protection des droits des l'homme, et le rôle, également croissant, joué par les organes de contrôle en vue de l'«objectivisation » de ces systèmes sont les aspects fondamentaux qu'émergent finalement de l'analyse des techniques d'interpretation des traités sur les droits de l'homme