Academic literature on the topic 'Musonio Rufo'

O conceito de “cidadão do mundo” foi reinventado na modernidade, como parte de um projeto de mundo humanista. Foi na antiguidade, porém, que, segundo Diógenes Laercio e outros, Diógenes o cínico pela primeira vez se declarou kosmopolites. O conceito foi depois enfatizado pelos estoicos, em especial Sêneca e Musonio Rufo. Alguns historiadores tendem a ver a campanha de Alexandre Magno como a aplicação do projeto de cidade universal no mundo conhecido. Este texto tem por objetivo problematizar algumas questões concernentes ao cosmopolitismo helenístico, do ponto de vista histórico-factual e quanto a sua concepção intelectual e teórica.

Abstract Background: CTX + dual HER2-targeting monoclonal antibodies (mAb) remains a standard of care for treatment (Tx) of both HER2+ early-stage and MBC. However, when the SOPHIA trial was launched, limited Tx options existed after progression on T, pertuzumab (P), and ado-trastuzumab emtansine. M, an Fc-engineered anti-HER2 mAb, targets the same epitope as T and exerts similar antiproliferative effects. M enhances CD16A-mediated ADCC compared to T. Furthermore, M treatment is associated with increased HER2-specific T- and B-cell responses and increased T-cell clonality compared to baseline. The phase 3 SOPHIA (NCT02492711) study demonstrated PFS benefit of M vs T, both + CTX, in HER2+ MBC pts. M improved PFS over T, with a 24% relative risk reduction (HR .76; 95% CI .59-.98; P=.033; median, 5.8 [95% CI 5.5-7.0] months (mo) vs 4.9 [95% CI 4.2-5.6] mo (Rugo HS, et al. JAMA Oncol 2021), resulting in FDA approval. Median OS after 270 mortality events (2nd interim analysis) was 21.6 mo with M vs 19.8 mo with T (HR .89; 95% CI .69-1.13; P=.33). Here we report final OS after 385 events, as well as updated safety.Methods: Pts with disease progression after ≥2 lines of anti-HER2 Tx, including P, and 1-3 lines of Tx for HER2+ MBC were randomized 1:1 to CTX + either M (15 mg/kg) or T (8 mg/kg loading dose, then 6 mg/kg), both given IV every 3 weeks. Randomization was stratified by number of metastatic sites (≤2, >2), lines of Tx for MBC (≤2, >2), and CTX choice (capecitabine, eribulin, gemcitabine, or vinorelbine). Sequential primary end points were central-blinded review of PFS and OS.Results: The intent-to-treat (ITT) population comprised 536 pts (M, 266; T, 270). At the median follow-up of 20.2 mo among all ITT pts, pts received a median of 7 cycles of M + CTX vs 6 cycles of T + CTX. Median OS after 385 events in the ITT population was 21.6 mo with M vs 21.9 mo with T (HR .95; 95% CI .77-1.17; P=.62; Table). Based on a prespecified, non-α-allocated exploratory analysis, a numerical OS advantage in favor of the M arm was observed in the subgroup of pts homozygous for the CD16A-158F low-affinity allele (median OS, 23.6 vs 19.2 mo; HR .72; 95% CI .52-1.00; nominal P=.05). In contrast, in the small subgroup of CD16A-158V homozygotes, median OS was longer for T vs M (31.1 mo vs 22.0 mo; HR 1.77; 95% CI 1.01-3.12; nominal P=.04). Grade ≥3 adverse events (AE) occurred in 146 pts (55.3%) receiving M vs 141 pts (53.0%) receiving T. Serious AEs were seen in 47 pts (17.8%) receiving M vs 51 pts (19.2%) receiving T. Incidence of infusion-related reactions was higher with M (36 [13.6%]) vs T (9 [3.4%]). Left ventricular dysfunction requiring delay or cessation of M/T administration occurred in 4 pts (1.5%) receiving M and in 7 pts (2.6%) receiving T. Conclusions: The median OS in the ITT population was not statistically different between the 2 arms. An exploratory analysis of CD16A genotyping indicates a numerical OS advantage in favor of M in F homozygous pts, along with a numerical OS advantage in favor of T in V homozygous pts. Safety of M + CTX was similar to previous reports and consistent with M FDA-approved label. Studies of M in HER2+ breast cancer pts with different CD16A allelic variants are warranted, including MARGOT, the neoadjuvant investigator-initiated study on the efficacy of M vs T in pts carrying F-allelic variants of CD16A. Median OSITT analysisPrespecified, non-α-allocated exploratory analysis (n=506)N=536CD16A-158F carriers (F/F and F/V)(n=437)CD16A-158F homozygotes (F/F)(n=192)CD16A-158F/V heterozygotes(n=245)CD16A-158V homozygotes (V/V)(n=69)aM + CTX, mo21.6 (n=266)23.3 (n=221)23.6 (n=102)21.3 (n=119)22.0 (n=37)T + CTX, mo21.9 (n=270)20.8 (n=216)19.2 (n=90)22.0 (n=126)31.1 (n=32)HR (95% CI)0.95 (0.77-1.17)0.86 (0.69-1.08)0.72 (0.52-1.00)0.96 (0.71-1.30)1.77 (1.01-3.12)P value0.620.19b0.05b0.78b0.04bAbbreviations: CTX, chemotherapy; HR, hazard ratio; ITT, intent to treat; M, margetuximab; mo, months; OS, overall survival; T, trastuzumab. Cutoff date: June 14, 2021. aThis subgroup was characterized by an imbalance in poor prognostic features. bNominal P value. Citation Format: Hope Rugo, Seock-Ah Im, Fatima Cardoso, Javier Cortes, Giuseppe Curigliano, Antonino Musolino, Mark D. Pegram, Thomas Bachelot, Gail S. Wright, Cristina Saura, Santiago Escrivá-de-Romaní, Michelino De Laurentiis, Gary N. Schwartz, Timothy Pluard, Francesco Ricci, William Gwin, III, Christelle Levy, Ursa Brown-Glaberman, Jean-Marc Ferrero, Maaike de Boer, Sung-Bae Kim, Katarína Petráková, Denise A. Yardley, Orit Freedman, Erik H. Jakobsen, Einav Nili Gal-Yam, Rinat Yerushalmi, Peter A. Fasching, Emily Ashley, Shengyan Hong, Minori Rosales, William J. Gradishar. Phase 3 SOPHIA study of margetuximab (M) + chemotherapy (CTX) vs trastuzumab (T) + CTX in patients (pts) with HER2+ metastatic breast cancer (MBC) after prior anti-HER2 therapies: Final overall survival (OS) analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD8-01.

RESUMENLos objetivos específicosson lossiguientes: (i) reconstruir en forma sistemática la relación entre λόγος y ἔθος/ἄσκησις desarrollada por Musonio Rufo en las Disertaciones 5 y 6; (ii) postular las reflexiones de Aristóteles sobre el problema de la habituación como un marco conceptual relevante para encuadrar el análisis de ambas disertaciones; (iii) analizar las posibles tensiones lógicas entre la concepción de Musonio de ἔθος/ἄσκησις y la concepción intelectualista de la acción humana defendida por la ortodoxia estoica. Sugeriré asimismo que el recurso a las Dissertationes de Epicteto puede ofrecer una respuesta tentativa a interrogantes no resueltos en las Disertaciones 5 y 6.PALABRAS CLAVEEJERCICIOS ESPIRITUALES, ESTOICISMO, INTELECTUALISMO, PSICOLOGÍA DE LA ACCIÓNABSTRACTThe specific goals are the following: (i) to put together in a systematic manner the relationship between λόγος and ἔθος/ἄσκησις presented by Musonius Rufus in Lectures 5 and 6; (ii) to propose Aristotle’s reflections on the problem of habituation as a relevant framework to make sense of both lectures; (iii) to analyze the possible logical conflicts between Musonius’ conception of ἔθος/ἄσκησις and the intellectualist conception of human agency defended by Stoic orthodoxy. I will further suggest that Epictetus’ Discourses may offer a tentative answer to questions that are left unanswered in Lectures 5 and 6.KEYWORDSSPIRITUAL EXERCISES, STOICISM, INTELLECTUALISM, PSYCHOLOGY OF ACTION

Questa tesi verte sulla maniera in cui i principali Stoici romani, vale a dire Seneca, Musonio Rufo, Epitteto, Ierocle e Marco Aurelio, concepivano e si servivano della nozione di καθῆκον (officium in latino), ereditata dalla tradizione stoica precedente. L’idea centrale che argomentiamo nel corso della tesi è che gli Stoici romani avevano tutti una concezione forte del καθῆκον, che testimonia una loro tendenza teorica comune, derivata dalla riflessione degli Stoici precedenti su questa nozione; inoltre, la prospettiva degli Stoici romani sul καθῆκον ci permette di conoscerne aspetti trascurati dalle fonti dossografiche apparentemente più informative a questo proposito: pensiamo, per esempio, al rapporto fra καθήκοντα e parenesi, all’importanza delle emozioni nel compimento dei καθήκοντα e all’antagonismo fra καθήκοντα e πάθη. Nella letteratura critica esistente sull’etica stoica e sul pensiero degli Stoici romani la tematica del καθῆκον è spesso considerata tangenzialmente rispetto ad altre, soprattutto perché, a eccezione di Epitteto, gli Stoici romani non tematizzano quasi mai la nozione di καθῆκον. Tuttavia, la nostra ricostruzione della rete concettuale del καθῆκον nella tradizione stoica ci permette di riconoscere la presenza, importante sebbene talora implicita, di questa nozione nella riflessione e nell’insegnamento degli stoici romani. Riusciamo così a delineare, per quanto possibile, la concezione del καθῆκον di questi filosofi. Le sujet de cette thèse est la façon dont les principaux stoïciens romains, tels que Sénèque, Musonius Rufus, Épictète, Hiéroclès et Marc Aurèle, ont conçu et employé la notion de καθῆκον (officium en latin), héritée de la tradition stoïcienne précédente. L’idée que nous y soutenons est que les stoïciens romains avaient tous une conceptualisation forte du καθῆκον, témoignant d’une tendance théorique commune entre eux qu’ils dérivaient de la réflexion des stoïciens précédents sur cette notion ; de plus, leur perspective sur le καθῆκον nous permet d’en connaître des aspects négligés par les sources doxographiques apparemment les plus éclairantes à ce sujet : nous pensons par exemple au lien entre καθήκοντα et parénèse, à l’importance des émotions dans l’accomplissement des καθήκοντα et à l’antagonisme entre καθήκοντα et πάθη. Dans la littérature critique existante concernant l’éthique stoïcienne ou bien la pensée des stoïciens romains, le thème du καθῆκον est souvent considéré marginalement par rapport à d’autres, surtout parce que, sauf pour Épictète, les autres stoïciens romains ne thématisent presque jamais la notion de καθῆκον. Cependant, une fois compris le réseau conceptuel du καθῆκον dans la tradition stoïcienne, nous parvenons à reconnaître la présence, importante bien que parfois implicite, de cette notion dans la réflexion et l’enseignement des stoïciens romains. Par cette méthode nous reconstruisons, dans la mesure du possible, la conceptualisation du καθῆκον par ces philosophes. This thesis deals with how the most important Roman Stoics, i.e. Seneca, Musonius Rufus, Epictetus, Hierocles and Marcus Aurelius, conceived and employed the notion of καθῆκον (officium in Latin), that they inherited from the previous Stoic tradition. Our claim is that all the Roman Stoics shared a strong conception of καθῆκον, in accordance with a general theoretical stance derived from the tradition of the earlier Stoics. Moreover, the perspective of the Roman Stoics on this topic allows us to discover some aspects of the καθῆκον that are neglected by the doxographic sources, apparently the most informative ones on this topic: we are thinking, for example, about the link between καθήκοντα and paraenesis, about the importance of emotions in performing καθήκοντα and about the opposition between καθήκοντα and πάθη. In the scholarship concerning Stoic ethics or the thought of the Roman Stoics, the theorical domain of the καθῆκον is often considered tangentially with regards to others, especially because the Roman Stoics almost never focus on the notion of καθῆκον, Epictetus being a notable exception. However, reconstructing the conceptual network of the καθῆκον in the Stoic tradition allows us to recognize its presence, important though sometimes implicit, in the Roman Stoics’ reflection and teaching. Thus, we manage to re-establish, insofar as possible, these philosophers’ conception of καθῆκον.