Academic literature on the topic 'Hybridation duale'

AbstractThe numerical simulation of non conservative system is a difficult challenge for two reasons at least. The first one is that it is not possible to derive jump relations directly from conservation principles, so that in general, if the model description is non ambiguous for smooth solutions, this is no longer the case for discontinuous solutions. From the numerical view point, this leads to the following situation: if a scheme is stable, its limit for mesh convergence will depend on its dissipative structure. This is well known since at least [1]. In this paper we are interested in the “dual” problem: given a system in non conservative form and consistent jump relations, how can we construct a numerical scheme that will, for mesh convergence, provide limit solutions that are the exact solution of the problem. In order to investigate this problem, we consider a multiphase flow model for which jump relations are known. Our scheme is an hybridation of Glimm scheme and Roe scheme.

Abstract BACKGROUND: Neoadjuvant therapy with antiHER-2 blockade is the standard of care for HER-2 positive early BC. The objective of this treatment is tumor downstaging to increase resectability and pathological complete response (pCR), a reliable surrogate endpoint for survival. Adding Trastuzumab (T) to chemotherapy resulted in an improvement in pCR, however, resistance to this agent is common and the incorporation of Pertuzumab (P) to the neoadjuvant scene demonstrated an increase in pCR in the Peony (39.3% vs 21.8%) and Neosphere trials (45.8% vs 29%). Across all studies, pCR is even higher in patients (pts) with negative hormonal receptor (HR) status (50%-63%) (3, 4). Tryphaena and Berenice found low rates of cardiotoxicity with T-P combination. Recently, TRAIN-2 data showed that anthracyclines and platinum have a similar pCR (67% vs 68%), but febrile neutropenia and cardiotoxicity is higher in the anthracycline group, concluding that omitting this therapy might be a preferred approach in the presence of dual HER2 blockade. Our study investigated the pCR benefit of dual HER2 blockade with anthracyclines and platinum in HER2 positive early BC. METHODS: We conducted a retrospective, unicenter, observational study of pts, treated with neoadjuvant T-P plus chemotherapy, in HER-2 positive early BC, between April 2015 and December 2022 at University Hospital A Coruña (Spain). The primary endpoint was total pCR in breast and axila (tpCR: ypT0/is ypN0). Secondary endpoints were: association between clinicopatological characteristics and pCR; and between cardiotoxicity and treatment pattern. Statistical analyses were conducted with Statistical Package for the Social Science (SPSS). RESULTS: During the study period, from April 2015 to May 2022, 154 pts were enrrolled. The median age was 51,3 years [range 26 – 799 years], all patients were female. Infiltrating ductal carcinoma was present in 92.2% pts, and 5.8% were inflammatory BC. At diagnosis, 11.7%, 61.7% and 26.6% had stages I, II and III, respectively, and 51.3% revealed axillary node involvement. Among observed cases, 94 (61%) were positive HR; 68 (45%) had histological grade 2 and 83 (53.9%) histological grade 3 tumors; and 151 pts (99.3%) presented a ki-67 level >20%. HER2 by immunohistochemistry (IHC) resulted in 3+ for 133 pts (86.9%) and in 2+ for 20 pts (13.1%), all of them with positive result by in situ hybridation (ISH). P-T were mostly combined with anthracyclines (64.9%). tpCR rate was 50.6%, and it was not significantly different according chemotherapy approach. tpCR was significantly higher among HR negative tumours (73.3%) compared with HR positive (36.2%) (p= 0.001), and in HER2 positive 3+ (55.6%) compared with HER2 positive 2+ (15%) tumours (p= 0.001). Achievement of tpCR was not significantly associated with tumor size, stage, histological grade and ki-67 level. Breast pCR was higher than tpCR (54.2%). 13 pts (8.4%) presented recurrence disease, in 76.9% of cases was a metastatic relapse. Cardiotoxicity was low during all stages of treatment and was not significantly associated with chemotherapy pattern. CONCLUSIONS: Neoadjuvant T-P plus chemotherapy with either anthracyclines or platinum therapy, demonstrated same efficacy and cardiac safety in our real-world study. pCR rates are lower in positive HR and HER2 positive 2+, needing more investigation with combination strategies including hormonotherapy, Our results are similar to data from randomized trials and other real-world efficacy studies, but we need more follow-up to identify late cardiotoxicity by anthracyclines and recurrences in positive HR tumors. Citation Format: Beatriz Alonso de Castro, Cristina Reboredo, Lourdes Calvo, Maria-Eva Perez-Lopez, Martin Igor Gomez Randulfe Rodriguez, Sofia silva diaz, Iria Parajo Vazquez, Silvia Antolin Novoa. Real-world efficacy of dual HER2-blockade in combination with anthracycline-containing and anthracycline-free neoadjuvant treatment in early breast cancer (BC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-07.

Abstract Abstract 4699 Objectives We have evaluated the possibility to use the new BD Cytometric Bead Array to detect the presence of the BCR-ABL fusion protein2 in peripheral blood samples with a routine blood hematology analyser, the Abbott Cell-Dyn Sapphire, for a quick identification of those positive samples, both at diagnosis and at follow up to detect the MRD. This pilot study was carried out on 5 samples with different level of BCR-ABL fusion protein2 plus 2 control samples positive and negative respectively: results were compared with those obtained with the BD FACScanto and the standard FISH analysis reference method. Methods Flow cytometry allows for the discrimination of particles on the basis of attributes such as size and fluorescence. BD Cytometric Bead Array (CBA) systems provide a way of coupling a soluble analyte or set of analytes with beads of known size and fluorescence, making it possible to detect analytes through flow cytometry.1 The BD” BCR-ABL Protein Kit uses this technology to detect BCR-ABL fusion proteins2 in human blood research samples. Cell-Dyn Sapphire is a routine automated hematology analyzer for full blood count. Moreover the system employs immuno-fluorescence analysis technology, similar to that used on a dedicated fluorescence flow cytometer, for analysis of MAb applications. BD FacScant is a routine dedicated flow cytometer using 6 fluorescence channels. FISH (Fluorescence In Situ Hybridation) is a cytogenetic technique using fluorescent probes that bind to only those part of the chromosome with which they show a high degree of sequence similarity in interphase nuclei and on metaphase chromosome. FISH detects and localizes the presence, the absence or the translocation of specific DNA sequences on chromosomes. In this patients' category, LSI bcr/abl dual fusion DNA probe hybridises to chromosome 22q11.2 (breakpoint cluster region SpectrumGreen) and to chromosome 9q34 (abl oncogene SpectrumOrange). In interphase nuclei of normal cells, the probe signals generally appear as two distinct signals of each colour. In the pathological cells with bcr/abl translocation, individual orange and green signals from the normal 9 and 22 chromosome and two orange/green fusion signals (one each from the derivative 9 and 22 chromosomes) is observed. We have analysed 200 nuclei in fluorescence microscopy for each sample. Statistical analyses were performed using the MedCalc program comparing the median fluorescence values obtained by the 2 cytometers and with the standard diagnostic procedure. Results Correlation of median fluorescence data between the BD FACScanto and the CD Sapphire is excellent with a Correlation coefficient r = 1,0000 and a Significance level P<0,0001 (Fig 1). The Box –and –whisker Multiple comparison graph of the CD method versus the FISH reference one is represented in Figure 2. The results of our pilot study demonstrate the robustness of this new diagnostic tool in detecting the presence of the BCR-ABL fusion protein2 in the routine Laboratory of Hematology. The main limit to use this tool is now represented by the high cost of the BD Cytometric Bead Array. Disclosures: No relevant conflicts of interest to declare.

Abstract Background Treatment related toxicity complicates outcome in elderly patients with AML (Estey et al. Blood. 2006). Conventionally, 7+3 induction (anthracycline plus cytarabine) results in Complete Remission rate of about 30%. Regimens with less toxicity, such as 10-days (d) schedule of DAC, seem promising with CR rate of 47% (Blum et al. PNAS. 2010). In secondary MDS derived AML, response prediction could be derived from mutation status in epigenetic modifiers (IDH1, IDH2, DNMT3 A, TET2), transcriptional regulators (RUNX1, CBL), and genes in spliceosome machinery, such as SF3B1 and SRSF2 (Husseinzadeh et al. American Society of Hem Meeting. Abstract # 1698. 2012). IDH-1 mutation is known to induce hypermethylator phenotype (fig 1) (Figueroa et al. Cancer Cell. 2010) and might be present in conjunction with SRSF2 mutations, an unique unreported molecular subset, feasible for exploring azanucleoside response prediction. Herein, we report a case of trisomy 8 MDS derived IDH1 and SRSF2 mutated AML who underwent rapid morphological blast differentiation in the context of acute differentiation syndrome while treated with 10 days (d) of hypomethylating dose of DAC. Methods A 61-year-old male with performance status (PS) = 3 presented with leukocytosis of 18.9 K/uL (peripheral blast 90%). He had a history of low-grade MDS diagnosed 2 years before AML transformation. After morphological confirmation of M5 AML, fluorescent in situ hybridation (FISH) revealed 81% nuclei with trisomy 8. Extracted DNA was tested with a custom-designed Leukemia Cancer Gene Mutation Panel using AmpliSeq™ technology and showed IDH1 c.394C>T(p.R132C) mutation (Fig. 2B) and c.284C>T(p.P95L) mutation of SRSF2 gene (Fig. 2C). DAC was initiated at 15 mg/m2 for a total of 10 days every 28 d cycle. Results By day 5 of cycle (C)1 of DAC treatment, brisk and significant rebound leukocytosis of 60 K/uL (Fig. 3) was observed, along with shortness of breath, hypoxemia and radiological evidence of floppy bilateral pulmonary infiltrates suggestive of acute-like differentiation syndrome. In addition to broad-spectrum antimicrobial and antifungal, dexamethasone at 4 mg intravenously (IV) every 8-hour (h) and hydroxyurea at 1 g orally every 8 h resulted in progressive normalization of peripheral blood count and hypoxemia after 48 h. Patient (pt) recovered from C1 and proceeded with C2 of treatment. A similar episode of brisk/robust leukocytosis was observed by day 5 of C2 requiring dexamethasone and hydroxyurea. Progressive morphological differentiation was observed to full mature and morphologically normal monocytes and neutrophil (Fig. 4). Pt expired as result of severe clostridium difficile colitis during C3 of DAC. Conclusions In our case, we observed robust acute differentiation syndrome characterized by rapid increase of WBC, shortness of breath and hypoxemia associated with azanucleoside treatment. Beside a novel association of IDH-1 and SRSF2 mutations, acute differentiation might suggest potential feature for azanucleoside response phenotype. Our case adds body of evidence of connection between epigenetic regulator and spliceosome mutations. Further studies on the impact of dual mutations in epigenetic reprogramming, leukemia transformation, and azanucleoside response will allow improved decision algorithm and therapeutic design. Disclosures: No relevant conflicts of interest to declare.

Notre thèse vise à répondre à la problématique : quel est le rôle du contrôle de gestion dans les Offices Publics de l’Habitat (OPH) confrontés à la complexité institutionnelle ? En étudiant ces organisations sujettes au pluralisme institutionnel (Greenwood et al., 2011), nous cherchons à enrichir la littérature (Château Terrisse, 2012 ; Boitier et Rivière, 2016 ; Renaud, 2017 ; Amans et al., 2020…) sur le rôle actif des dispositifs de contrôle de gestion dans l’hybridation de logiques potentiellement incompatibles. L’ancrage théorique de la thèse se situe dans le courant des microfondations de la théorie néo-institutionnelle (Thornton et Ocasio, 1999 ; Thornton et al., 2012).Notre démarche méthodologique est structurée en deux temps. Nous réalisons d’abord une étude qualitative sur Gesthome, un OPH en pleine mutation confronté à quatre logiques institutionnelles (bureaucratique, politique, de marché et professionnelle). Cette étude qualitative mobilise plusieurs méthodes de recueil et d’analyse des données : 16 entretiens semi-directifs auprès des parties prenantes internes et externes de cette organisation, l’analyse de 26 documents et des archives de 713 pages ainsi qu’une observation participante durant 3 ans (3 carnets de notes de 120 pages chacun). Ce travail de terrain minutieux est réalisé dans le cadre d’une Convention Industrielle de Formation par la Recherche (CIFRE).Pour l’analyse de contenu, nous utilisons le logiciel d’analyse qualitative N’Vivo. Puis, en complément de l’étude qualitative, une étude quantitative est menée auprès de 32 OPH sur le territoire français afin de vérifier la transférabilité des résultats obtenus au sein de Gesthome.Nous montrons que les dispositifs de contrôle de gestion permettent la coexistence des logiques, favorisent l’hybridation duale, voire « triale » des logiques en servant de base à des compromis. Il ressort de notre étude au sein de Gesthome et de l’étude quantitative quatre compromis (Amans et al., 2020) conduisant au polymorphisme organisationnel (Renaud, 2017) : un compromis des logiques politique et de marché, un compromis des logiques politique et professionnelle, un compromis des logiques de marché et professionnelle et enfin un compromis entre les trois logiques. En outre, nos travaux apportent un éclairage sur le pilotage des OPHLM encore balbutiant dans l'état de l'art
Our thesis aims to answer the question: What is the role of management control in Public Housing Offices (OPH) in the face of institutional complexity? By studying these organizations subject to institutional pluralism (Greenwood et al., 2011), we seek to enrich the literature (Château Terrisse, 2012 ; Boitier and Rivière, 2016; Renaud, 2017 ; Amans et al., 2020…) on the role active management control devices in the hybridization of potentially incompatible logics. The theoretical grounding of the thesis is in the current of micro-foundations of neo-institutional theory (Thornton and Ocasio, 1999; Thornton et al., 2012).Our methodological approach is structured in two stages. We first carry out a qualitative study on Gesthome, a rapidly changing OPH, confronted with four institutional logics (bureaucratic, political, market and professional). This qualitative study mobilizes several methods of data collection and analysis: 16 semi-structured interviews with internal and external stakeholders of this organization, the analysis of 26 documents and archives of 713 pages as well as participant observation during 3 years (3 notebooks of 120 pages each). This meticulous fieldwork is carried out within the framework of an Industrial Research Training Agreement (CIFRE).For content analysis, we use the qualitative analysis software N'Vivo. Then, in addition to the qualitative study, a quantitative study is conducted with 32 DPOs on French territory in order to verify the transferability of the results obtained within Gesthome.We show that the management control devices allow the coexistence of logics, promote the dual hybridization or even “triale” of logics, by serving as a basis for compromises. Our study within Gesthome and the quantitative study show four compromises (Amans et al., 2020) leading to organizational polymorphism (Renaud, 2017): a compromise of political and market logics, a compromise of political and professional, a compromise between market and professional logics and finally a compromise between the three logics. In addition, our work sheds light on the piloting of OPH still in their infancy in the state of the art