Le "De bello ciuili" de Lucain, une parole en mutation (de la rhétorique républicaine à une poétique de la guerre civile)

Les deux premiers chants de Lucain témoignent d une utilisation novatrice des discours directs dans l épopée. Présentés sous forme de triades de paroles juxtaposées le dialogue n est plus possible dans le monde du De bello ciuili- dont l objectif et le genre sont similaires, ils incitent le lecteur-auditeur de l Antiquité, rompu aux joutes oratoires des concours de déclamation, à les comparer. L examen de deux de ces groupes de discours sert de préliminaire à une enquête plus large sur la parole rhétorique, puis sur la parole poétique.Dans la confrontation des discours de la première triade (Curion / César /Laelius, au chant I) se lit la condamnation de l éloquence traditionnelle fondée sur des valeurs éthiques universellement partagées. Elle est supplantée par une rhétorique sophistique qui redéfinit, exclusivement en fonction des intérêts personnels de l orateur, tout ce qui a trait au droit, au juste ou à la citoyenneté, notions problématiques dans le contexte de perversion morale du bellum ciuile. L efficacité de cette nouvelle éloquence est signalée par le succès des trois suasoires qui sont à l origine des grands tournants narratifs de l œuvre : Curion décide César à entrer définitivement dans l affrontement civil (Chant I), Cicéron pousse Pompée à donner le signal du début du combat à Pharsale (Chant VII) et Pothin persuade Ptolémée d assassiner Magnus (Chant VIII).Dans la comparaison des trois paroles prophétiques de la fin du livre I auxquelles répondent les trois discours du début du chant suivant, effusions angoissées de Romains anonymes (les femmes, les hommes et le vieillard), se dessine un art poétique destiné à justifier les choix génériques du poète pour traiter son sujet. Conformant son œuvre à la médiocrité humaine des masses, il doit renoncer au genre tragique (discours des femmes) ainsi qu à la célébration épique des héros (discours des hommes) et s efforcer de proposer, à l instar du vieillard qui se remémore le passé pour anticiper le futur (le plus long discours de l épopée, rappelant, par sa place et son sujet, l ilioupersis d Enée), une épopée historique qui cherche à percer l opacité du monde de la guerre civile, dans lequel les dieux ne sont plus anthropomorphes. Empruntant leur esthétique du déchiffrement du réel aux Piérides ovidiennes, ces poétesses humaines, rivales des divines Muses (Métamorphoses V), Lucain refonde alors la persona de son uates. Chantre d un genre nouveau, pour une épopée renouvelée, le piéridique uates du De bello ciuili qui ne peut plus être omniscient puisque les pensées et les actions des superi lui sont inconnaissables- refuse le patronage des divinités traditionnelles de la poésie, promet à son héros César, non la gloire mais l exécration éternelle et proclame avec défi, qu il ne devra lui-même l éternité qu à la seule puissance de son talent personnel, divines Muses et grands guerriers héroïques des œuvres du passé ayant été congédiés par la guerre civile.The first two books of Lucan reveal an innovative use of direct speech in epic. Presented as contiguous speech triads dialogs being impossible in the realm of De bello ciuili whose purpose and genre are similar, they lead the ancient reader-listener, used to oral debates typical of declamation contests, to compare them. The investigation of two of these speech groups is our first step to a larger inquiry on rhetoric speech, then on poetic speech.Confronting the speech of the first triad (Curion/Caesar/Laelius in book I) reveals the end of traditional eloquence based on universal ethic values. It is superseded by a sophistic rhetoric that redefines (exclusively according to the speaker's private interests) whatever relates to law, justice or citizenship problematic concepts in the perverse moral context of bellum ciuile. The efficiency of this new eloquence is highlighted by the success of the three suasory performances which cause the work's main narrative turns: Curion convinces Caesar to definitely take part to the civil war (book I), Cicero leads Pompeus to launch the battle at Pharsalia (book VII) and Pothinus persuades Ptolemy to murder Magnus (book VIII).Comparing the three prophetic speeches at the end of book I (which mirror the three speeches at the beginning of the following book), anxious complains of anonimous Romans (the women, the men and the elderly), we identify an art of poetry aimed at motivating the generic choices made by the poet to handle his subject. Working along the lines of the human depravity of masses, he may not employ neither the tragic style (the speech of women) nor the epic celebration of heroes (the speech of men), but must suggest as the old man remembers the past to anticipate the future (the longest speech of the epic reminds Eneas Ilioupersis by means of its place and subject) an historical epic aiming at enlightening the opaque world of civil war, in which the gods are no longer anthropomorphic. Borrowing their deciphering aesthetic to Ovids Pierides, human female poets rivaling the godly Muses (Metamorphosis V), Lucan reinvents the persona of his uates. Promoting a new genre, for a renewed epic, the 'pieridic' uates of De Bello Ciuili, which can no longer be omniscient since the superi's thoughts and deeds are out of his reach refuses to worship the traditional poetry deities, swears to his 'hero' Caesar not the glory but the eternal hatred and defiantly proclaims that he himself will deserve eternity only through his own talent, the godly Muses and great heroic warriors of ancient works having been dismissed by civil war.PARIS-EST-Université (770839901) / SudocPARIS12-Bib. électronique (940280011) / SudocSudocFranceF

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Le "De bello ciuili" de Lucain, une parole en mutation : de la rhétorique républicaine à une poétique de la guerre civile

Les deux premiers chants de Lucain témoignent d’une utilisation novatrice des discours directs dans l’épopée. Présentés sous forme de triades de paroles juxtaposées –le dialogue n’est plus possible dans le monde du De bello ciuili- dont l’objectif et le genre sont similaires, ils incitent le lecteur-auditeur de l’Antiquité, rompu aux joutes oratoires des concours de déclamation, à les comparer. L’examen de deux de ces groupes de discours sert de préliminaire à une enquête plus large sur la parole rhétorique, puis sur la parole poétique.Dans la confrontation des discours de la première triade (Curion / César /Laelius, au chant I) se lit la condamnation de l’éloquence traditionnelle fondée sur des valeurs éthiques universellement partagées. Elle est supplantée par une rhétorique sophistique qui redéfinit, exclusivement en fonction des intérêts personnels de l’orateur, tout ce qui a trait au droit, au juste ou à la citoyenneté, notions problématiques dans le contexte de perversion morale du bellum ciuile. L’efficacité de cette nouvelle éloquence est signalée par le succès des trois suasoires qui sont à l’origine des grands tournants narratifs de l’œuvre : Curion décide César à entrer définitivement dans l’affrontement civil (Chant I), Cicéron pousse Pompée à donner le signal du début du combat à Pharsale (Chant VII) et Pothin persuade Ptolémée d’assassiner Magnus (Chant VIII).Dans la comparaison des trois paroles prophétiques de la fin du livre I auxquelles répondent les trois discours du début du chant suivant, effusions angoissées de Romains anonymes (les femmes, les hommes et le vieillard), se dessine un art poétique destiné à justifier les choix génériques du poète pour traiter son sujet. Conformant son œuvre à la médiocrité humaine des masses, il doit renoncer au genre tragique (discours des femmes) ainsi qu’à la célébration épique des héros (discours des hommes) et s’efforcer de proposer, à l’instar du vieillard qui se remémore le passé pour anticiper le futur (le plus long discours de l’épopée, rappelant, par sa place et son sujet, l’ilioupersis d’Enée), une épopée historique qui cherche à percer l’opacité du monde de la guerre civile, dans lequel les dieux ne sont plus anthropomorphes. Empruntant leur esthétique du déchiffrement du réel aux Piérides ovidiennes, ces poétesses humaines, rivales des divines Muses (Métamorphoses V), Lucain refonde alors la persona de son uates. Chantre d’un genre nouveau, pour une épopée renouvelée, le ‘piéridique’ uates du De bello ciuili qui ne peut plus être omniscient –puisque les pensées et les actions des superi lui sont inconnaissables- refuse le patronage des divinités traditionnelles de la poésie, promet à son ‘héros’ César, non la gloire mais l’exécration éternelle et proclame avec défi, qu’il ne devra lui-même l’éternité qu’à la seule puissance de son talent personnel, divines Muses et grands guerriers héroïques des œuvres du passé ayant été congédiés par la guerre civile.The first two books of Lucan reveal an innovative use of direct speech in epic. Presented as contiguous speech triads – dialogs being impossible in the realm of De bello ciuili – whose purpose and genre are similar, they lead the ancient reader-listener, used to oral debates typical of declamation contests, to compare them. The investigation of two of these speech groups is our first step to a larger inquiry on rhetoric speech, then on poetic speech.Confronting the speech of the first triad (Curion/Caesar/Laelius in book I) reveals the end of traditional eloquence based on universal ethic values. It is superseded by a sophistic rhetoric that redefines (exclusively according to the speaker's private interests) whatever relates to law, justice or citizenship – problematic concepts in the perverse moral context of bellum ciuile. The efficiency of this new eloquence is highlighted by the success of the three suasory performances which cause the work's main narrative turns: Curion convinces Caesar to definitely take part to the civil war (book I), Cicero leads Pompeus to launch the battle at Pharsalia (book VII) and Pothinus persuades Ptolemy to murder Magnus (book VIII).Comparing the three prophetic speeches at the end of book I (which mirror the three speeches at the beginning of the following book), anxious complains of anonimous Romans (the women, the men and the elderly), we identify an ‘art of poetry’ aimed at motivating the generic choices made by the poet to handle his subject. Working along the lines of the human depravity of masses, he may not employ neither the tragic style (the speech of women) nor the epic celebration of heroes (the speech of men), but must suggest – as the old man remembers the past to anticipate the future (the longest speech of the epic reminds Eneas’ Ilioupersis by means of its place and subject) – an historical epic aiming at enlightening the opaque world of civil war, in which the gods are no longer anthropomorphic. Borrowing their deciphering aesthetic to Ovids’ Pierides, human female poets rivaling the godly Muses (Metamorphosis V), Lucan reinvents the persona of his uates. Promoting a new genre, for a renewed epic, the 'pieridic' uates of De Bello Ciuili, which can no longer be omniscient – since the superi's thoughts and deeds are out of his reach – refuses to worship the traditional poetry deities, swears to his 'hero' Caesar not the glory but the eternal hatred and defiantly proclaims that he himself will deserve eternity only through his own talent, the godly Muses and great heroic warriors of ancient works having been dismissed by civil war

Novel missense mutations in PRPF6 cause autosomal dominant retinitis pigmentosa with incomplete penetrance and impairment of PRPF6 protein localization within the nucleus

International audiencePurpose : To characterize clinically and genetically two families with autosomal dominant retinitis pigmentosa (adRP) with new causative mutations in PRPF6, a gene described to be associated with this condition in a single study.Methods : A large adRP and sporadic RP cohort was screened for mutations using targeted next-generation sequencing. Clinical investigations included visual acuity and visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, full-fields and multifocal electroretinogram (ERG) recording. Cellular localization of GFP-tagged wild-type or mutated PRPF6 in HEK293 transfected cells was observed by confocal microscopy.Results : Two heterozygous mutations c.680C>T (p.Thr227Met) and c.514C>T (p.Arg172Trp) in PRPF6 were identified in an adRP family and in a sporadic RP patient, respectively. Both variants segregated with the disease phenotype and were predicted to be pathogenic. An asymptomatic heterozygous carrier of the p.Arg172Trp mutation was also identified. In HEK293 transfected cells, an abnormal accumulation of the two mutated GFP-PRPF6, but not wild-type, within Cajal bodies was observed.Conclusions : We identified two novel causative mutations in PRPF6, responsible for autosomal dominant retinitis pigmentosa with variation of penetrance. Presence of asymptomatic carriers is common among patients with adRP, especially when the cause of the disease is due to a mutation in splicing factors’ genes. The two mutations identified lead to a mislocalization of the PRPF6 protein within the nucleus, which could indicate a possible alteration in the assembly or recycling of the tri-snRNP complex of the spliceosome

Novel missense mutations in PRPF6 cause autosomal dominant retinitis pigmentosa with incomplete penetrance and impairment of PRPF6 protein localization within the nucleus

International audiencePurpose : To characterize clinically and genetically two families with autosomal dominant retinitis pigmentosa (adRP) with new causative mutations in PRPF6, a gene described to be associated with this condition in a single study.Methods : A large adRP and sporadic RP cohort was screened for mutations using targeted next-generation sequencing. Clinical investigations included visual acuity and visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, full-fields and multifocal electroretinogram (ERG) recording. Cellular localization of GFP-tagged wild-type or mutated PRPF6 in HEK293 transfected cells was observed by confocal microscopy.Results : Two heterozygous mutations c.680C>T (p.Thr227Met) and c.514C>T (p.Arg172Trp) in PRPF6 were identified in an adRP family and in a sporadic RP patient, respectively. Both variants segregated with the disease phenotype and were predicted to be pathogenic. An asymptomatic heterozygous carrier of the p.Arg172Trp mutation was also identified. In HEK293 transfected cells, an abnormal accumulation of the two mutated GFP-PRPF6, but not wild-type, within Cajal bodies was observed.Conclusions : We identified two novel causative mutations in PRPF6, responsible for autosomal dominant retinitis pigmentosa with variation of penetrance. Presence of asymptomatic carriers is common among patients with adRP, especially when the cause of the disease is due to a mutation in splicing factors’ genes. The two mutations identified lead to a mislocalization of the PRPF6 protein within the nucleus, which could indicate a possible alteration in the assembly or recycling of the tri-snRNP complex of the spliceosome

A 4.6 Mb Inversion Leading to PCDH15-LINC00844 and BICC1-PCDH15 Fusion Transcripts as a New Pathogenic Mechanism Implicated in Usher Syndrome Type 1

International audienceUsher type 1 syndrome is a rare autosomal recessive disorder involving congenital severe-to-profound hearing loss, development of vision impairment in the first decade, and severe balance difficulties. The PCDH15 gene, one of the five genes implicated in this disease, is involved in 8-20% of cases. In this study, we aimed to identify and characterize the two causal variants in a French patient with typical Usher syndrome clinical features. Massively parallel sequencing-based gene panel and screening for large rearrangements were used, which detected a single multi-exon deletion in the PCDH15 gene. As the second pathogenic event was likely localized in the unscreened regions of the gene, PCDH15 transcripts from cultured nasal cells were analyzed and revealed a loss of junction between exon 13 and exon 14. This aberration could be explained by the identification of two fusion transcripts, PCDH15-LINC00844 and BICC1-PCDH15, originating from a 4.6 Mb inversion. This complex chromosomal rearrangement could not be detected by our diagnostic approach but was instead characterized by long-read sequencing, which offers the possibility of detecting balanced structural variants (SVs). This finding extends our knowledge of the mutational spectrum of the PCDH15 gene with the first ever identification of a large causal paracentric inversion of chromosome 10 and illustrates the utility of screening balanced SVs in an exhaustive molecular diagnostic approach

Atypical Foveal Hypoplasia in Best Disease

Purpose: To determine the prevalence and characteristics of foveal hypoplasia (also called fovea plana) in patients with Best disease using spectral-domain (SD) optical coherence tomography (OCT) and OCT-angiography (OCT-A). Design: A retrospective observational study including patients diagnosed with Best disease. Subjects and Participants: Fifty-nine eyes of thirty-two patients (fifteen females (46.9%) and seventeen males (53.1%), p = 0.9) diagnosed with Best disease were included. Patients’ eyes were categorized into two groups: Eyes with a fovea plana appearance (‘FP group’) and eyes without fovea plana appearance (‘no FP group’), based on the foveal appearance on B-scan SD-OCT. Methods and Main Outcome Measures: Cross-sectional OCT images were assessed for the persistence of inner retinal layers (IRL) and OCT-A was analyzed for the presence of a foveal avascular zone (FAZ), the size of which was determined when applicable. Results: Overall, 16 eyes (27.1%) of 9 patients had a fovea plana appearance (‘FP group’) with the persistence of IRL, and 43 eyes (72.9%) of 23 patients did not have fovea plana appearance (‘no FP group’). Among FP eyes, OCT-A performed in 13 eyes showed bridging vessels through the FAZ in 100% of eyes with OCT-A. Using Thomas classification, 14 out of the 16 eyes with fovea plana (87.5%) had atypical foveal hypoplasia, and the 2 others (12.5%) had a grade 1b fovea plana. Conclusion: In our series, foveal hypoplasia was present in 27.1% of patients with Best disease. OCT-A showed bridging vessels through the FAZ in all eyes. These findings highlight the microvascular changes associated with Best disease, which can be an early sign of the disease in patients with a family history

Enrichment of LOVD-USHbases with 152 USH2A Genotypes Defines an Extensive Mutational Spectrum and Highlights Missense Hotspots

International audienceAlterations of USH2A, encoding usherin, are responsible for more than 70% of cases of Usher syndrome type II (USH2), a recessive disorder that combines moderate to severe hearing loss and retinal degeneration. The longest USH2A transcript encodes usherin isoform b, a 5,202-amino-acid transmembrane protein with an exceptionally large extracellular domain consisting notably of a Laminin N-terminal domain and numerous Laminin EGF-like (LE) and Fibronectin type III (FN3) repeats. Mutations of USH2A are scattered throughout the gene and mostly private. Annotating these variants is therefore of major importance to correctly assign pathogenicity. We have extensively genotyped a novel cohort of 152 Usher patients and identified 158 different mutations, of which 93 are newly described. Pooling this new data with the existing pathogenic variants already incorporated in USHbases reveals several previously unappreciated features of the mutational spectrum. We show that parts of the protein are more likely to tolerate single amino acid variations, whereas others constitute pathogenic missense hotspots. We have found, in repeated LE and FN3 domains, a nonequal distribution of the missense mutations that highlights some crucial positions in usherin with possible consequences for the assessment of the pathogenicity of the numerous missense variants identified in USH2A

The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A

International audienceUsher syndrome is an autosomal recessive disorder characterized by congenital hearing loss combined with retinitis pigmentosa, and in some cases, vestibular areflexia. Three clinical subtypes are distinguished, and MYO7A and USH2A represent the two major causal genes involved in Usher type I, the most severe form, and type II, the most frequent form, respectively. Massively parallel sequencing was performed on a cohort of patients in the context of a molecular diagnosis to confirm clinical suspicion of Usher syndrome. We report here 231 pathogenic MYO7A and USH2A genotypes identified in 73 Usher type I and 158 Usher type II patients. Furthermore, we present the ACMG classification of the variants, which comprise all types. Among them, 68 have not been previously reported in the literature, including 12 missense and 16 splice variants. We also report a new deep intronic variant in USH2A. Despite the important number of molecular studies published on these two genes, we show that during the course of routine genetic diagnosis, undescribed variants continue to be identified at a high rate. This is particularly pertinent in the current era, where therapeutic strategies based on DNA or RNA technologies are being developed

NAITRE study on the impact of conditional cash transfer on poor pregnancy outcomes in underprivileged women: protocol for a nationwide pragmatic cluster-randomised superiority clinical trial in France

International audienceIntroduction Prenatal care is recommended during pregnancy to improve neonatal and maternal outcomes. Women of lower socioeconomic status (SES) are less compliant to recommended prenatal care and suffer a higher risk of adverse perinatal outcomes. Several attempts to encourage optimal pregnancy follow-up have shown controversial results, particularly in high-income countries. Few studies have assessed financial incentives to encourage prenatal care, and none reported materno-fetal events as the primary outcome. Our study aims to determine whether financial incentives could improve pregnancy outcomes in women with low SES in a high-income country.Methods and analysis This pragmatic cluster-randomised clinical trial includes pregnant women with the following criteria: (1) age above 18 years, (2) first pregnancy visit before 26 weeks of gestation and (3) belonging to a socioeconomically disadvantaged group. The intervention consists in offering financial incentives conditional on attending scheduled pregnancy follow-up consultations. Clusters are 2-month periods with random turnover across centres. A composite outcome of maternal and neonatal morbidity and mortality is the primary endpoint. Secondary endpoints include maternal or neonatal outcomes assessed separately, qualitative assessment of the perception of the intervention and cost-effectiveness analysis for which children will be followed to the end of their first year through the French health insurance database. The study started in June 2016, and based on an expected decrease in the primary endpoint from 18% to 14% in the intervention group, we plan to include 2000 women in each group.Ethics and dissemination Ethics approval was first gained on 28 September 2014. An independent data security and monitoring committee has been established. Results of the main trial and each of the secondary analyses will be submitted for publication in a peer-reviewed journal.Trial registration number NCT02402855; pre-results