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Control of heat exhaust is essential for the operation of power producing fusion reactors. Here, we present results of heat exhaust feedback control experiments in JET and AUG. In JET, we demonstrate the first X-point radiator (XPR) control in DD and DT discharges using argon seeding. In AUG, we improve the XPR control with nitrogen seeding, resulting in achieving the first detached L-H and H-L transition (in a single discharge). The controllers are designed using a model-based design procedure. The required models are obtained experimentally using perturbative (system identification) experiments. We study the dynamic response of the XPR to various seeding species and varying operating conditions. We find that the sensitivity (relative gain) of the XPR varies as function the height of the radiator inside the confined region but that the relative phase is consistent for all operating points. In AUG, the XPR is also less sensitive to impurity seeding changes for higher heating powers. In JET, we show that the XPR dynamics are the same for DD and DT plasmas. However, we observe that XPR control is only possible with argon and not with neon. The results show that a controller might well be designed in earlier stages of operation of a future device, but remains applicable and can be further tuned for full power operation.

This study presents results from particle transport modelling for D/T ratio control experiments conducted during the JET DTE3 campaign. TRANSP interpretative and JETTO predictive simulations for D and T densities were performed and their results are discussed. Despite using simplified models based on Bohm-gyroBohm transport, the simulations incorporate self-consistent sources and impurities and cover the full radial range. The simplified models effectively reproduced the evolution of electron density and neutron rates. However, the predicted D/T ratio evolution responded to control requests faster than what was experimentally observed, suggesting that the employed models possess certain limitations. Specific cases involving swapped gas injection species were also studied, highlighting the potential applicability of the proposed methodology in future experimental scenarios. TRANSP interpretative analysis indicates that a Real-Time (RT) scheme employing simplified quasi-neutrality and Zeff estimations can be implemented with high degree of reliability. JETTO predictive analysis suggests that a simplified modelling approach for the behaviour of the future RT controllers of D/T mixture can be effective. Such an approach involves using measured temperatures, omitting explicit modelling of the SOL physics, and adopting simplified assumptions for the particle transport.

Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial ( n =113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m 2 . More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6–43.9%)) vs AZA (14.3% (5.4–28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50–80%); AZA, 70% (50–80%)) or time to progression (PAN+AZA, 70% (40–90%); AZA, 70% (40–80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen.

The understanding of the time-scales and associated transient behavior of fusion exhaust plasmas plays a crucial role in its dynamic modeling and its control. This work presents an overview of experimental investigations of the exhaust dynamics in TCV, MAST-U, ASDEX-Upgrade, WEST, DIII-D, and JET. From the presented experiments, a clear picture arises on properties of the exhaust dynamics across machines. Particularly, we observe that the scrape-off layer equilibrates on fast time-scales ( > 70 Hz) and that exhaust dynamics measured in response to gas valve modulations mostly behave smoothly and linearly, with similarities across devices, across scenarios (H-mode, L-mode), injected species, and injection locations. The measurements presented have formed the basis for systematic exhaust control on the considered devices. We now present this database for the essential validation of dynamic exhaust models for reactor design and control.

We monitored 133 high-risk allo-SCT recipients for 6 months after transplant for EBV reactivation by quantitative real-time PCR. Rituximab was given as pre-emptive therapy for viremia >1000 copies/mL. The 1-year cumulative incidence of EBV reactivation was 29.4% (95% confidence interval (CI): 18–40) in patients monitored due to initial high-risk characteristics ( n =93) and 31.8% (95% CI: 19.7–44) in those followed because of the development of refractory GVHD ( n =40). Overall response rate to Rituximab was 83%. Nine patients (9.6%) developed post-transplant lymphoproliferative disorder (PTLD) at a median of +62 days after SCT. Eight of them showed a concomitant CMV reactivation. Second SCT was the only risk factor associated with EBV infection and PTLD in multivariate analysis (hazard ratio (HR) 2.6 (95% CI: 1.1–6.4; P =0.04) and HR 6.4 (95%CI: 1.3–32; P =0.02)). The development of EBV reactivation was not associated with non-relapse mortality or OS ( P =0.97 and P =0.84, respectively).

This study aimed to characterize the incidence, etiology and outcome of infectious episodes in patients with steroid refractory acute GvHD (SR-GvHD). The cohort included 127 adults treated with inolimomab (77%) or etanercept (23%) owing to acute 2–4 SR-GvHD, with a response rate of 43% on day +30 and a 4-year survival of 15%. The 1-year cumulative incidences of bacterial, CMV and invasive fungal infection were 74%, 65% and 14%, respectively. A high rate (37%) of enterococcal infections was observed. Twenty patients (15.7%) developed BK virus-hemorrhagic cystitis and five percent had an EBV reactivation with only one case of PTLD. One-third of long-term survivors developed pneumonia by a community respiratory virus and/or encapsulated bacteria, mostly associated with chronic GvHD. Infections were an important cause of non-relapse mortality, with a 4-year incidence of 46%. In multivariate analysis, use of rituximab in the 6 months before SCT (hazard ratio; HR 4.2; 95% confidence interval; CI 1.1–16.3), severe infection before SR-GvHD onset (HR 5.8; 95% CI 1.3–26.3) and a baseline C-reactive protein >15 UI/mL (HR 2.9; 95% CI 1.1–8.5) were associated with infection-related mortality. High rates of opportunistic infections with remarkable mortality warrant further efforts to optimize long-term outcomes after SR-GvHD.

Background Epigenetic therapy, using hypomethylating agents (HMA), is known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy and/or allogeneic stem cell transplantation. However, response rates to HMA are low and there is an unmet need in finding prognostic and predictive biomarkers of treatment response and overall survival. We performed global methylation analysis of 75 patients with high-risk MDS and secondary AML who were included in CETLAM SMD-09 protocol, in which patients received HMA or intensive treatment according to age, comorbidities and cytogenetic. Results Unsupervised analysis of global methylation pattern at diagnosis did not allow patients to be differentiated according to the cytological subtype, cytogenetic groups, treatment response or patient outcome. However, after a supervised analysis we found a methylation signature defined by 200 probes, which allowed differentiating between patients responding and non-responding to azacitidine (AZA) treatment and a different methylation pattern also defined by 200 probes that allowed to differentiate patients according to their survival. On studying follow-up samples, we confirmed that AZA decreases global DNA methylation, but in our cohort the degree of methylation decrease did not correlate with the type of response. The methylation signature detected at diagnosis was not useful in treated samples to distinguish patients who were going to relapse or progress. Conclusions Our findings suggest that in a subset of specific CpGs, altered DNA methylation patterns at diagnosis may be useful as a biomarker for predicting AZA response and survival.

We prospectively compared two strategies of allogeneic PBSCT from HLA-identical siblings in adults with poor-risk AML or myelodysplastic syndrome with >5% marrow blasts in an early disease status (AML or refractory anemia with excess blasts (RAEB type 2) in first remission after chemotherapy or untreated RAEB type 1). Based only on age, all consecutive patients were offered one of two specific transplant protocols. Patients ⩽50 years old received conventional high-dose conditioning with cyclophosphamide-TBI and use of CD34+-selected PBSCT (CTCD34+ group), while patients aged >50 years received a reduced-intensity conditioning (RIC) with fludarabine and oral busulphan (FB-RIC). Seventy-five patients entered the study (35 in the CTCD34+ and 39 in the FB-RIC group). The median follow-up was >4 years in both groups. The 4-year non-relapse mortality (NRM) was 19 and 20%, respectively ( P =0.8). Relapse and survival were also equivalent in both groups. These results suggest that in this setting, the expected high NRM in elderly patients can be reduced with an RIC regimen.