Simondon reconsidered : An interview with Nathalie Simondon

Nel presente contributo proponiamo un’intervista a Nathalie Simondon, responsabile dell’edizione dell’opera di Gilbert Simondon, al fine di fare luce sui temi di ecologia, enciclopedismo, transdisciplinarità e umanismo nella produzione filosofica di Gilbert Simondon.In this paper we propose an interview with Nathalie Simondon, responsible for the edition of Gilbert Simondon’s work, in order to shed a light on the topics of ecology, encyclopedism, transdisciplinarity and humanism in Gilbert Simondon’s philosophical production

Attraverso Deleuze e Simondon: ontogenesi, processo e relazione

The aim of this work is to provide a cartography of the notion of individuation, in its relations with the dimension of the pre-individual, working between Gilles Deleuze and Gilbert Simondon, through a path of “fraying” of the human. Ultimately, we would like to show how it is possible to re-semantize the vexata quaestio of the “End of Man”, re-reading it as a problem of borders and multiple layers, always active and in becoming. In order to highlight this constitutive interrelation between the field of the pre-personal and the processes of individuation, we will analyze the concepts of difference, affectivity and “ontological communism”.Obiettivo del presente contributo è tracciare una cartografia della nozione di individuazione, nella sua relazionalità con la dimensione del pre-individuale, lavorando tra il pensiero di Gilles Deleuze e Gilbert Simondon, attraverso un percorso di ripensamento dell’idea di umanità. Si vorrebbe cioè mostrare come sia possibile risemantizzare la vexata quaestio della “Fine dell’Uomo”, rileggendola piuttosto come un problema di con-fini e di margini, sempre attivi e divenienti. Al fine di mettere in luce questa costitutiva interrelazione fra il campo del pre-personale e dei processi di individuazione, si prenderanno in analisi i concetti di differenza, affettività e di “comunismo ontologico”

Prevalence of resistance-associated substitutions to NS3, NS5A and NS5B inhibitors at DAA-failure in hepatitis C virus in Italy from 2015 to 2019

: Despite the high efficacy of direct-acting antivirals (DAAs), the selection of resistance-associated substitutions (RASs) after virological failure of hepatitis C virus (HCV) DAAs can impair the cure of chronic HCV. The aim of the study was to characterize RASs after virological failure of DAAs in Italy over the years. Within the Italian network VIRONET-C, the change in prevalence of NS3/4A-NS5A-NS5B RASs was retrospectively evaluated in patients who failed a DAA regimen over the years 2015-2019. NS3, NS5A and NS5B Sanger sequencing was performed using homemade protocols and the geno2pheno system was used to define HCV-genotype/subtype and predict drug resistance. The changes in the prevalence of RASs over time were evaluated using the chi-square test for trend. Predictors of RASs at failure were analysed by logistic regression. Among 468 HCV-infected patients, HCV genotype 1 was the most prevalent (1b in 154, 33% and 1a in 109, 23%). DAA regimens were: ledipasvir (LDV)/sofosbuvir (SOF) in 131 patients (28%), daclatasvir (DCV)/SOF in 109 (23%), ombitasvir/paritaprevir/ritonavir+dasabuvir (3D) in 89 (19%), elbasvir (EBR)/grazoprevir (GRZ) in 52 (10.5%), velpatasvir (VEL)/SOF in 53 (11%), glecaprevir (GLE)/pibrentasvir (PIB) in 27 (6%) and ombitasvir/paritaprevir/ritonavir (2D) in 7 (1.5%); ribavirin was administered in 133 (28%). The NS5A fasta sequence was available for all patients, NS5B and NS3/4A both for 93%. The prevalence of NS5A and NS3/4A RASs significantly declined from 2015 to 2019; NS5B RAS remained stable. Independent predictors of any RASs included older age and genotype 1a (vs G2 and vs G4). Notably, at least partial susceptibility to all the agents included in the GLE/PIB and VEL/SOF/Voxilaprevir (VOX) combinations was predicted in >95% of cases. As RASs remain common at the failure of DAAs, their identification could play a crucial role in optimizing re-treatment strategies. In Italy RAS prevalence has been decreasing over the years and susceptibility to the latest developed drug combinations is maintained in most cases

DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Philosophy as a fiery imperative: Deleuze, Practical philosophy

Nel presente articolo tenteremo di mettere in luce in che modo la filosofia di Gilles Deleuze intrattenga un rapporto ineludibile con il tema delle pratiche, volendo mostrare il profondo interesse che il pensatore francese nutre nei confronti dei πράγματα. Per seguire un tale itinerario, al contempo speculativo e pragmatico, ci soffermeremo su alcuni concetti chiave dell’opera deleuziana (creazione, invenzione, problematicismo, drammatizzazione e genesi), che crediamo possano contribuire a mettere in luce nel suo agire evenemenziale la dimensione “praticalista” del pensiero di Deleuze.In this article we will try to highlight how Gilles Deleuze's philosophy is deeply connected with the topic of practices and we will thematize his profound interest towards πράγματα. Following this line of thought, which is both speculative and pragmatic, we will focus on some key concepts of Deleuze's work (creation, invention, problematicism, dramatisation and genesis), which we believe can contribute to show the "practicalist" dimension of Deleuze's philosophy, in its evenemential dimension

Health professionals before the crime of injuries, obligations and homework

Introducción: Las lesiones ocasionadas en la comisión de un delito están tipificadas y caracterizadas en el código penal argentino, constituyendo un capítulo en el que los profesionales de la salud están obligados a realizar las denuncias correspondientes para salvaguardar la integridad de la víctima. La presentación pretende clarificar aspectos protocolares específicos del procedimiento legal que los profesionales de la salud que asistan a víctimas de lesiones deben seguir.Introduction: The injuries caused in the commission of a crime are typified and characterized in the Argentine penal code, constituting a chapter in which health professionals are obliged to make the corresponding complaints to safeguard the integrity of the victim. The presentation aims to clarify specific protocol aspects of the legal procedure that health professionals assisting injury victims must follow.Facultad de Odontologí

ABM documentation and odd protocol in economics: a bibliometric analysis

Since the ¯rst agent-based models (ABM), the scienti¯c community has been interested in making not only the results of computational models understandable but also the modeling description, to facilitate their replication. The form that has been adopted to a greater extent has been the ODD (Overview, Design concepts, and Details) protocol, which provides a generic structure for its documentation. This protocol provides a way to clearly explain the procedures and interactions of the complex systems to be analyzed, with applications that have spread across di®erent disciplines. This study presents a bibliometric analysis using Scopus database of the articles that emerged from the ¯rst publication of this protocol in 2006. The results show that the use of this form of documenting has grown in Economics, but its participation remains stable in relative terms. Results also show that the top journal both in number of articles and impact is JASSS, but it is not observed that there is a greater dissemination toward speci¯c Economics journals or that it is used for a greater number of topics. Finally, it is found that there is a common core in Economics' ABM literature, with a bias toward methodological articles in the articles that follow the ODD protocol while there is a bias towards articles on economic models in those that do not follow this protocol.Fil: Alvarez Zanelli, Emiliano. Universidad de la República; UruguayFil: Brida, Juan Gabriel. Universidad de la Republica; UruguayFil: London, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Económicas y Sociales del Sur. Universidad Nacional del Sur. Departamento de Economía. Instituto de Investigaciones Económicas y Sociales del Sur; Argentin