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KEYNOTE-522 demonstrated statistically significant improvements in pathological complete response (pCR) with neoadjuvant pembrolizumab plus chemotherapy and event-free survival (EFS) with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in patients with high-risk, early-stage triple-negative breast cancer (TNBC). Prior studies have shown the prognostic value of the residual cancer burden (RCB) index to quantify the extent of residual disease after neoadjuvant chemotherapy. In this preplanned exploratory analysis, we assessed RCB distribution and EFS within RCB categories by treatment group. A total of 1174 patients with stage T1c/N1-2 or T2-4/N0-2 TNBC were randomized 2 : 1 to pembrolizumab 200 mg or placebo every 3 weeks given with four cycles of paclitaxel + carboplatin, followed by four cycles of doxorubicin or epirubicin + cyclophosphamide. After surgery, patients received pembrolizumab or placebo for nine cycles or until recurrence or unacceptable toxicity. Primary endpoints are pCR and EFS. RCB is a prespecified exploratory endpoint. The association between EFS and RCB was assessed using a Cox regression model. Pembrolizumab shifted patients into lower RCB categories across the entire spectrum compared with placebo. There were more patients in the pembrolizumab group with RCB-0 (pCR), and fewer patients in the pembrolizumab group with RCB-1, RCB-2, and RCB-3. The corresponding hazard ratios (95% confidence intervals) for EFS were 0.70 (0.38-1.31), 0.92 (0.39-2.20), 0.52 (0.32-0.82), and 1.24 (0.69-2.23). The most common first EFS events were distant recurrences, with fewer in the pembrolizumab group across all RCB categories. Among patients with RCB-0/1, more than half [21/38 (55.3%)] of all events were central nervous system recurrences, with 13/22 (59.1%) in the pembrolizumab group and 8/16 (50.0%) in the placebo group. Addition of pembrolizumab to chemotherapy resulted in fewer EFS events in the RCB-0, RCB-1, and RCB-2 categories, with the greatest benefit in RCB-2. These findings demonstrate that pembrolizumab not only increased pCR rates, but also improved EFS among most patients who do not have a pCR. • KEYNOTE-522 evaluated neoadjuvant pembrolizumab + chemotherapy/adjuvant pembrolizumab versus neoadjuvant chemotherapy alone in early TNBC. • Neoadjuvant pembrolizumab + chemotherapy/adjuvant pembrolizumab significantly improved pCR/EFS versus neoadjuvant chemotherapy alone. • We explored the effect of adding pembrolizumab to chemotherapy on outcomes by RCB category. • Pembrolizumab not only increased pCR rates, but also improved EFS among many patients who do not have a pCR. • Findings support neoadjuvant pembrolizumab + chemotherapy/adjuvant pembrolizumab as a standard of care treatment in early TNBC. [ABSTRACT FROM AUTHOR]

• Extensive literature survey on two-phase flow experiment using 12 m or longer vertical tube was conducted. • Experiments were conducted on two-phase flow regime observation, void fraction and frictional pressure drop measurement over a long channel length under high-pressure brine conditions. • The transition of flow regime took place at higher superficial gas velocity under brine conditions. • Through drift-flux model analysis, change in gas velocity under brine conditions was confirmed. • New frictional pressure drop model at high-pressure two-phase flow under brine conditions is proposed. The offshore methane hydrate production test conducted in Japan has demonstrated a successful production of methane gas from marine gas hydrates using depressurization methods. The method produces methane gas by dissociating methane hydrate, which is stable at low temperature and high pressure conditions, by lowering the bottom-hole pressure in the wellbore. Under this method, stable control of bottom-hole pressure is necessary to ensure continuous methane gas production. Therefore, understanding the behavior of upward gas–liquid two-phase flow, involving gas-brine mixture, in a wellbore is essential for the proper pressure drop evaluation in the production line. In the present study, void fraction and frictional pressure drop behaviors under nitrogen-brine two-phase flow conditions is investigated using the high-pressure test facility of 52.7 mm inner diameter and 28 m height. The measured void fraction was assessed using drift-flux model, and the results showed that the decrease in bubble diameter under bubbly flow in gas-brine two-phase flow conditions resulted in decrease in bubble rise velocity and uniformity of bubble distribution. It was also found that, under bubbly flow in gas-brine mixture, the frictional pressure drop tends to further decrease with elevation. Based on these findings and obtained experimental dataset, the new frictional pressure model for gas-brine two-phase flow under high-pressure conditions is developed in the present study. [ABSTRACT FROM AUTHOR]