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Treatment of relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a great challenge. Aiming to evaluate the combination of venetoclax and hypomethylating agents (HMAClax) for the treatment of relapse of myeloid malignancies after alloHSCT, we retrospectively collected data from 32 patients treated at 11 German centers. Venetoclax was applied with azacitidine (n = 13) or decitabine (n = 19); 11 patients received DLI in addition. HMAClax was the first salvage therapy in 8 patients. The median number of cycles per patient was 2 (1–19). All but 1 patient had grade 3/4 neutropenia. Hospital admission for grade 3/4 infections was necessary in 23 patients (72%); 5 of these were fatal. In 30 evaluable patients, overall response rate (ORR) was 47% (14/30, 3 CR MRDneg, 5 CR, 2 CRi, 1 MLFS, 3 PR). ORR was 86% in first salvage patients versus 35% in later salvage patients (p = 0.03). In 6 patients with molecular relapse (MR), ORR was 67% versus 42% in patients with hematological relapse (HR) (n = 24, p = n.s.). After a median follow-up of 8.4 months, 25 patients (78%) had died and 7 were alive. Estimated median overall survival was 3.7 months. Median survival of patients with HMAClax for first versus later salvage therapy was 5.7 and 3.4 months (p = n.s.) and for patients with MR (not reached) compared to HR (3.4 months, p = 0.024). This retrospective case series shows that venetoclax is utilized in various different combinations, schedules, and doses. Toxicity is substantial and patients who receive venetoclax/HMA combinations for MR or as first salvage therapy derive the greatest benefit.
Ultra-intense MeV photon and neutron beams are indispensable tools in many research fields such as nuclear, atomic and material science as well as in medical and biophysical applications. For astrophysical applications aimed on laboratory investigations of the r-processes responsible for the production of heavy elements in explosive supernova scenarios, neutron fluxes in excess of 1021 n/(cm2 s) are required. These ultra-high fluxes are unattainable with existing conventional reactor- and accelerator-based facilities. Currently discussed concepts for the generation of high-flux neutron beams are based on ultra-high-power multi-petawatt lasers operating at >1023 W/cm2 intensities. Here, we present a novel concept for the efficient generation of γ and neutron beams based on relativistic laser interactions with a long-scale near critical density plasma at 1019 W/cm2 intensity. New experimental insights in the laser-driven generation of ultra-intense well-directed multi-MeV beams of photons with fluences of >1012 ph/sr and a ultra-high intense neutron source with >1010 neutrons per shot are presented. Optimization of the target-set based on the gamma-driven nuclear reactions promises an ultra-high neutron fluence of >1011 n/cm2 and corresponding neutron peak-fluxes of ∼1022 n/(cm2 s) already at moderate relativistic laser intensities.
Machine learning entails a broad range of techniques that have been widely used in Science and Engineering since decades. High-energy physics has also profited from the power of these tools for advanced analysis of colliders data. It is only up until recently that Machine Learning has started to be applied successfully in the domain of Accelerator Physics, which is testified by intense efforts deployed in this domain by several laboratories worldwide. This is also the case of CERN, where recently focused efforts have been devoted to the application of Machine Learning techniques to beam dynamics studies at the Large Hadron Collider (LHC). This implies a wide spectrum of applications from beam measurements and machine performance optimisation to analysis of numerical data from tracking simulations of non-linear beam dynamics. In this paper, the LHC-related applications that are currently pursued are presented and discussed in detail, paying also attention to future developments.
Background: Patients undergoing allogeneic stem cell transplantation (aSCT) are at high risk to develop an invasive fungal disease (IFD). Optimisation of antifungal prophylaxis strategies may improve patient outcomes and reduce treatment costs.
Objectives: To analyse the clinical and economical impact of using continuous micafungin as antifungal prophylaxis.
Patients/Methods: We performed a single-centre evaluation comparing patients who received either oral posaconazole with micafungin as intravenous bridging as required (POS-MIC) to patients who received only micafungin (MIC) as antifungal prophylaxis after aSCT. Epidemiological, clinical and direct treatment cost data extracted from the Cologne Cohort of Neutropenic Patients (CoCoNut) were analysed.
Results: Three hundred and thirteen patients (97 and 216 patients in the POS-MIC and MIC groups, respectively) were included into the analysis. In the POS-MIC and MIC groups, median overall length of stay was 42 days (IQR: 35–52 days) vs 40 days (IQR: 35–49 days; p = .296), resulting in median overall costs of €42,964 (IQR: €35,040–€56,348) vs €43,291 (IQR: €37,281 vs €51,848; p = .993), respectively. Probable/proven IFD in the POS-MIC and MIC groups occurred in 5 patients (5%) vs 3 patients (1%; p = .051), respectively. The Kaplan-Meier analysis showed improved outcome of patients in the MIC group at day 100 (p = .037) and day 365 (p < .001) following aSCT.
Conclusions: Our study results demonstrate improved outcomes in the MIC group compared with the POS-MIC group, which can in part be explained by a tendency towards less probable/proven IFD. Higher drug acquisition costs of micafungin did not translate into higher overall costs.
Non-forest ecosystems, dominated by shrubs, grasses and herbaceous plants, provide ecosystem services including carbon sequestration and forage for grazing, yet are highly sensitive to climatic changes. Yet these ecosystems are poorly represented in remotely-sensed biomass products and are undersampled by in-situ monitoring. Current global change threats emphasise the need for new tools to capture biomass change in non-forest ecosystems at appropriate scales. Here we assess whether canopy height inferred from drone photogrammetry allows the estimation of aboveground biomass (AGB) across low-stature plant species sampled through a global site network. We found mean canopy height is strongly predictive of AGB across species, demonstrating standardised photogrammetric approaches are generalisable across growth forms and environmental settings. Biomass per-unit-of-height was similar within, but different among, plant functional types. We find drone-based photogrammetry allows for monitoring of AGB across large spatial extents and can advance understanding of understudied and vulnerable non-forested ecosystems across the globe.
Surface temperature is a fundamental parameter of Earth’s climate. Its evolution through time is commonly reconstructed using the oxygen isotope and the clumped isotope compositions of carbonate archives. However, reaction kinetics involved in the precipitation of carbonates can introduce inaccuracies in the derived temperatures. Here, we show that dual clumped isotope analyses, i.e., simultaneous ∆47 and ∆48 measurements on the single carbonate phase, can identify the origin and quantify the extent of these kinetic biases. Our results verify theoretical predictions and evidence that the isotopic disequilibrium commonly observed in speleothems and scleractinian coral skeletons is inherited from the dissolved inorganic carbon pool of their parent solutions. Further, we show that dual clumped isotope thermometry can achieve reliable palaeotemperature reconstructions, devoid of kinetic bias. Analysis of a belemnite rostrum implies that it precipitated near isotopic equilibrium and confirms the warmer-than-present temperatures during the Early Cretaceous at southern high latitudes.
Dielectrons are an excellent probe for the QCD matter created in created in ultra-relativistic heavy-ion collisions, since they are emitted during the whole evolution of the collision and do not interact strongly with the medium. To isolate the QGP signals, measurement of the dielectron production in vacuum and its modifications due to the presence of cold nuclear matter is necessary. We present and discuss results from a low magnetic field detector setup in proton-proton collisions at √s = 13 TeV, as well as the measurement of dielectron production in pp, p-Pb, and Pb-Pb collisions at √sNN = 5 TeV.
Heavy quarks are useful probes to investigate the properties of the Quark-Gluon Plasma (QGP) produced in heavy-ion collisions at the LHC, since they are produced in initial hard scattering processes. To single out the signals that are characteristic of the QGP, it is nevertheless crucial to understand the primordial heavy-quark production in vacuum, and to disentangle hot from cold nuclear matter effects. Moreover, observations of collective effects in high-multiplicity pp and p-Pb collisions show surprising similarities with those in heavy-ion collisions. Heavy-flavour production in such collisions could give further insight into the underlying processes. The heavy-flavour production can be studied with e+e− pairs from correlated semileptonic decays of heavy-flavour hadrons. Compared to single heavy-flavour measurements, the dielectron yield contains information about the initial kinematical correlations between the charm and anti-charm quarks, which is otherwise not accessible, and is sensitive to soft heavy-flavour production. We report results on correlated e+e− pairs in pp collisions recorded by the ALICE detector at different collision energies. The production of heavy quarks is discussed by comparing the yield of dielectrons from heavy-flavour hadron decays as a function of invariant mass, pair transverse momentum and distance of closest approach to the primary vertex with different Monte Carlo event generators. The heavy-flavour production cross sections are also presented. Results from high-multiplicity pp collisions at √s=13 TeV and the status of the p-Pb analysis at √sNN=5.02 TeV are reported as well.
Heavy quarks are useful probes to investigate the properties of the Quark-Gluon Plasma (QGP) produced in heavy-ion collisions at the LHC, since they are produced in initial hard scattering processes. To single out the signals that are characteristic of the QGP, it is nevertheless crucial to understand the primordial heavy-quark production in vacuum, and to disentangle hot from cold nuclear matter effects. Moreover, observations of collective effects in high-multiplicity pp and p-Pb collisions show surprising similarities with those in heavy-ion collisions. Heavy-flavour production in such collisions could give further insight into the underlying processes. The heavy-flavour production can be studied with e+e− pairs from correlated semileptonic decays of heavy-flavour hadrons. Compared to single heavy-flavour measurements, the dielectron yield contains information about the initial kinematical correlations between the charm and anti-charm quarks, which is otherwise not accessible, and is sensitive to soft heavy-flavour production. We report results on correlated e+e− pairs in pp collisions recorded by the ALICE detector at different collision energies. The production of heavy quarks is discussed by comparing the yield of dielectrons from heavy-flavour hadron decays as a function of invariant mass, pair transverse momentum and distance of closest approach to the primary vertex with different Monte Carlo event generators. The heavy-flavour production cross sections are also presented. Results from high-multiplicity pp collisions at √s=13 TeV and the status of the p-Pb analysis at √sNN=5.02 TeV are reported as well.
Heavy quarks are useful probes to investigate the properties of the Quark-Gluon Plasma (QGP) produced in heavy-ion collisions at the LHC, since they are produced in initial hard scattering processes. To single out the signals that are characteristic of the QGP, it is nevertheless crucial to understand the primordial heavy-quark production in vacuum, and to disentangle hot from cold nuclear matter effects. Moreover, observations of collective effects in high-multiplicity pp and p-Pb collisions show surprising similarities with those in heavy-ion collisions. Heavy-flavour production in such collisions could give further insight into the underlying processes. The heavy-flavour production can be studied with e+e− pairs from correlated semileptonic decays of heavy-flavour hadrons. Compared to single heavy-flavour measurements, the dielectron yield contains information about the initial kinematical correlations between the charm and anti-charm quarks, which is otherwise not accessible, and is sensitive to soft heavy-flavour production. We report results on correlated e+e− pairs in pp collisions recorded by the ALICE detector at different collision energies. The production of heavy quarks is discussed by comparing the yield of dielectrons from heavy-flavour hadron decays as a function of invariant mass, pair transverse momentum and distance of closest approach to the primary vertex with different Monte Carlo event generators. The heavy-flavour production cross sections are also presented. Results from high-multiplicity pp collisions at √s=13 TeV and the status of the p-Pb analysis at √sNN=5.02 TeV are reported as well.