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Background The value of adding carboplatin (Cb) to neoadjuvant chemotherapy for TNBC is debated. Current evidence supports the association between Cb use and increased pathological complete response (pCR) rate. However, treatment schedules and doses adopted in randomized trials were not always consistent with those used in clinical practice. Methods Clinicopathological data of TNBC (ER & PgR Results 166 patients were included: 61% treated with AT, 39% with AT+Cb (all patients in this group received Cb AUC2 weekly administered concomitantly to the taxane segment). Main characteristics: median age 50 yrs, ductal histology 93%, grade 3 90%, cT > 2cm 86%, cN + 57%, median TILs 10%, median Ki67 60%, BRCA mutated 10%. After propensity score matching, pCR rate was significantly higher for AT+Cb vs AT: 52% vs 31% (OR 2.39 95%CI 1.04-5.50, p = 0.040). In multivariable analysis, treatment with AT+Cb maintained an independent association with pCR: OR 2.51 95%CI 1.03-6.11, P = 0.043. The achievement of pCR was significantly associated with improved disease-free survival (HR 0.16, 95%CI 0.06-0.45). No difference in DFS was observed comparing AT+Cb vs AT: HR 0.99, 95%CI 0.44-2.25. Conclusions We confirmed in a clinical practice setting the association of Cb-containing neoadjuvant chemotherapy with higher pCR rates. Additional data are needed to clarify the impact on long-term survival. These data support the conditional positive recommendation for Cb inclusion in neoadjuvant chemotherapy for TNBC provided by the Italian Association of Medical Oncology Guidelines on Breast Cancer. Funding Has not received any funding. Disclosure M.V. Dieci: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Celgene; Advisory / Consultancy: Genomic Health. V. Guarneri: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.

Recent interest in a severe accident management scheme known as ‘In-Yessel Retention’ has created the need to establish the coolability limits of large, inverted geometries. In this paper, full-scale simulations conducted at UCSB's ULPU facility are examined at the microscopic level. Because of the peculiar geometry, it has become possible to directly visualize the boiling transition phenomenon, and with the help of microthermocouples to quantitatively identify the mechanism of dryout. Altogether, a new boiling transition regime was identified, with a significant coupling between overall systems dynamics and the microphenomena. This leads the way to the a priori prediction of critical heat flux and factors that may influence it.

The ACOPO experiment simulates natural convection heat transfer from volumetrically heated pools at a half-scale reactor lower head geometry (hemispherical). New data for internal Rayleigh numbers of up to 1016 are presented, correlated and discussed, in relation to other available correlations. These ACOPO results confirm a key component of the in-vessel retention severe accident management strategy for an AP600-like design, as recently established in DOE/ID-10460.

The conditions of the MAGICO-2000 experiment are extended to more broadly investigate the regimes of premixing, and the corresponding internal structures of mixing zones. With the help of the data and numerical simulations using the computer code PM-ALPHA, we can distinguish extremes of behavior dominated by inertia and thermal effects—we name these the inertia and thermal regimes, respectively. This is an important distinction that should guide future experiments aimed at code verification in this area. Interesting intermediate behaviors are also delineated and discussed.

Lower head integrity under steam explosion loads in an AP600-like reactor design is considered. The assessment is the second part of an evaluation of the in-vessel retention idea as a severe accident management concept, the first part (DOE:ID-10460) dealing with thermal loads. The assessment is conducted in terms of the risk oriented accident analysis methodology (ROAAM), and includes the comprehensive evaluation of all relevant severe accident scenarios, melt conditions and timing of release from the core region, fully three-dimensional mixing and explosion wave dynamics, and lower head fragility under local, dynamic loading. All of these factors are brought together in a ROAAM probabilistic framework to evaluate failure likelihood. The conclusion is that failure is 'physically unreasonable'. © 1999 Elsevier Science S.A. All rights reserved.

An overall verification approach for the PM-ALPHA code is presented and implemented. The approach consists of a stepwise testing procedure focused principally on the multifield aspects of the premixing phenomenon. Breakup is treated empirically, but it is shown that, through reasonable choices of the breakup parameters, consistent interpretations of existing integral premixing experiments can be obtained. The present capability is deemed adequate for bounding energetics evaluations.

As computations of transient, multidimensional, multiphase flows are becoming increasingly more realistic, so increases the demand for their detailed experimental validation. Key in this task is the evolution of flow patterns, and the usual approaches of local measurements are inherently limited in meeting this demand. In this paper, we demonstrate the particular suitability of flash X-ray radiography, and the feasibility of reliably quantifying the radiographs of flow regions of various sizes, from microscopic to rather large scale.

This work addresses certain fundamental aspects of the premixing phase of steam explosions. At issue are the multifield interaction aspects under highly transient, multidimensional conditions and in the presence of strong phase changes. They are addressed in an experiment (the MAGICO-2000) involving well-characterized particle clouds mixing with water and detailed measurements on both external and internal characteristics of the mixing zone. Both cold and hot (up to 1500°C) particle clouds are considered in conjunction with saturated and subcooled water pools. The PM-ALPHA code is used as an aid in interpreting the experimental results and the exercise reveals good predictive capabilities for it.

The ACOPO experiment simulates natural convection heat transfer from volumetrically heated pools, at a half-scale reactor lower head geometry (hemispherical). Data for Rayleigh numbers of up to 2·1016, from the first round of experiments, are presented in this paper. The results are in substantial agreement with those of the mini-ACOPO proof-of-concept experiment. Moreover, it is shown that these ACOPO results confirm a key component of the in-vessel retention capability for an AP600-like design, as recently established in DOE/ID-10460.

Three recently published premixing experiments, the Magico, mixa , and Faro , are discussed comparatively, and two of them, the Magico and Faro , are analyzed with the help of the computer code Pm-alpha . The results of these analyses are shown to provide quantitative interpretations of the data, and to suggest conditions/measurements in further experiments to enhance the insights thus obtained. Also, a quantitative radiography technique is described and applied to Magico for the measurement of chordal-averaged void fractions in the mixing zone. The results are in excellent agreement with Pm-Alpha predictions, thus confirming the previously reported good comparisons with the local (point) measurements of Flute .

The thermal field in a reactor vessel downcomer and resulting thermal/stress response in the adjacent reactor vessel wall during high-pressure safety injection are examined, especially with regard to departures from one-dimensional behavior. Similarity solutions for the stratification (in the cold leg) that creates the downcomer plumes, and scaling considerations for the thermal conduction and stress fields in the vessel wall are developed to provide generalized criteria for the adequacy of the one-dimensional treatment.

This paper describes the first attempt to experimentally quantify the multiphase transient associated with the premixing of steam explosions — a hot particulated (heavy) phase falling, in film boiling, into a coolant pool, which is thus forced to rapid vaporization. The process is characterized by mixing-zone-averaged and local void-fraction transients, as well as mixing-front advancement histories, and the data are found to be in good agreement with predictions carried out with our PM-ALPHA code. In particular, these tests confirm the predicted water depletion phenomenon which is a crucial factor in limiting the energetics of large-scale steam explosions.