Clonal Activation of Akt in Low-Risk MDS Patients with Del(5q) treated with Lenalidomide

The activation of inositide signalling pathways, such as Akt/mTOR, has been demonstrated in high-risk MDS (1). Lenalidomide is currently used in the treatment of del(5q) low-risk MDS patients, where it may suppress the del(5q) clone and restore a normal erythropoiesis, via inhibition of Akt phosphorylation (2). Here, we studied the expression of inositide signalling molecules in 6 low-risk MDS patients who were given Lenalidomide by immunocytochemistry and Real-Time PCR. In our case series, 4 out of 6 del(5q) low-risk MDS patients responded to Lenalidomide and showed an activation of erythropoiesis, in that Beta-Globin levels increased, as compared with baseline. Moreover, these subjects also displayed an activation of PI-PLCgamma1 and Akt. Interestingly, Akt resulted to be specifically phosphorylated in cells not showing the 5q deletion, hinting at a clonal activation of this pathway. The 2 non responder patients early discontinued Lenalidomide for adverse events, and for these patients neither a clinical assessment of Lenalidomide effect, nor a molecular analysis, were possible. Our data show Akt/PI-PLCgamma1 activation during Lenalidomide treatment, and confirm the activation of erythropoiesis in responder patients. In addition, our results indicate that Akt is specifically phosphorylated in the 5q+ clone. Therefore, it is conceivable that Lenalidomide strengthens the proliferation of the 5q+ clone, whilst the del(5q) clone undergoes an apoptotic process, allowing the restoration of the normal erythropoiesis. This is extremely important, not only for MDS pathogenesis, but also for the development of innovative targeted therapies

A real-life study of daratumumab-bortezomib-dexamethasone (D-VD) in lenalidomide exposed/refractory multiple myeloma patients: a report from the Triveneto Myeloma Working Group

Treatment of lenalidomide refractory (Len-R) multiple myeloma (MM) patients still represents an unmet clinical need. In the last years, daratumumab-bortezomib-dexamethasone (D-VD) combination was extensively used in this setting, even though only a small fraction of Len-R patients was included in the pivotal trial. This real-life study aimed to evaluate the efficacy and safety of the D-VD regimen in a cohort that exclusively enrolled Len exposed or refractory MM patients. The study cohort included 57 patients affected by relapsed/refractory MM. All patients were previously exposed to Len, with 77.2% being refractory. The overall response rate (ORR) was 79.6% with 43% of cases obtaining at least a very good partial response (VGPR). The D-VD regimen showed a favorable safety profile, with low frequency of grade 3–4 adverse events, except for thrombocytopenia observed in 21.4% of patients. With a median follow-up of 13 months, median progression-free survival (PFS) was 17 months. No significant PFS differences were observed according to age, ISS, LDH levels, type of relapse, and high-risk FISH. Len exposed patients displayed a PFS advantage as compared to Len refractory patients (29 vs 16 months, p = 0.2876). Similarly, patients treated after Len maintenance showed a better outcome as compared to patients who had received a full-dose Len treatment (23 vs 13 months, p = 0.1728). In conclusion, our real-world data on D-VD combination showed remarkable efficacy in Len-R patients, placing this regimen as one of the standards of care to be properly taken into account in this MM setting

Two-particle azimuthal correlations in photonuclear ultraperipheral Pb+Pb collisions at 5.02 TeV with ATLAS

Two-particle long-range azimuthal correlations are measured in photonuclear collisions using 1.7 nb−1 of 5.02 TeV Pb+Pb collision data collected by the ATLAS experiment at the CERN Large Hadron Collider. Candidate events are selected using a dedicated high-multiplicity photonuclear event trigger, a combination of information from the zero-degree calorimeters and forward calorimeters, and from pseudorapidity gaps constructed using calorimeter energy clusters and charged-particle tracks. Distributions of event properties are compared between data and Monte Carlo simulations of photonuclear processes. Two-particle correlation functions are formed using charged-particle tracks in the selected events, and a template-fitting method is employed to subtract the nonflow contribution to the correlation. Significant nonzero values of the secondand third-order flow coefficients are observed and presented as a function of charged-particle multiplicity and transverse momentum. The results are compared with flow coefficients obtained in proton-proton and proton-lead collisions in similar multiplicity ranges, and with theoretical expectations. The unique initial conditions present in this measurement provide a new way to probe the origin of the collective signatures previously observed only in hadronic collisions

Search for supersymmetry in events with four or more charged leptons in 139 fb−1 of √ s= 13 TeV pp collisions with the ATLAS detector

A search for supersymmetry in events with four or more charged leptons (electrons, muons and τ -leptons) is presented. The analysis uses a data sample corresponding to 139 fb−1 of proton-proton collisions delivered by the Large Hadron Collider at √s = 13 TeV and recorded by the ATLAS detector. Four-lepton signal regions with up to two hadronically decaying τ -leptons are designed to target several supersymmetric models, while a general five-lepton signal region targets any new physics phenomena leading to a final state with five charged leptons. Data yields are consistent with Standard Model expectations and results are used to set upper limits on contributions from processes beyond the Standard Model. Exclusion limits are set at the 95% confidence level in simplified models of general gauge-mediated supersymmetry, excluding higgsino masses up to 540 GeV. In R-parity-violating simplified models with decays of the lightest supersymmetric particle to charged leptons, lower limits of 1.6 TeV, 1.2 TeV, and 2.5 TeV are placed on wino, slepton and gluino masses, respectively

Search for R-parity-violating supersymmetry in a final state containing leptons and many jets with the ATLAS experiment using √s=13 TeV proton–proton collision data

A search for R-parity-violating supersymmetry in final states characterized by high jet multiplicity, at least one isolated light lepton and either zero or at least three btagged jets is presented. The search uses 139 fb−1 of √s =13 TeV proton–proton collision data collected by the ATLAS experiment during Run 2 of the Large Hadron Collider. The results are interpreted in the context of R-parity-violating supersymmetry models that feature gluino production, topsquark production, or electroweakino production. The dominant sources of background are estimated using a data-driven model, based on observables at medium jet multiplicity, to predict the b-tagged jet multiplicity distribution at the higher jet multiplicities used in the search. Machine-learning techniques are used to reach sensitivity to electroweakino production, extending the data-driven background estimation to the shape of the machine-learning discriminant. No significant excess over the Standard Model expectation is observed and exclusion limits at the 95% confidence level are extracted, reaching as high as 2.4 TeV in gluino mass, 1.35 TeV in topsquark mass, and 320 (365) GeV in higgsino (wino) mass

Search for bottom-squark pair production in pp collision events at s=13 TeV with hadronically decaying τ -leptons, b -jets, and missing transverse momentum using the ATLAS detector

A search for pair production of bottom squarks in events with hadronically decaying τ-leptons, b-tagged jets, and large missing transverse momentum is presented. The analyzed dataset is based on proton-proton collisions at √s=13 TeV delivered by the Large Hadron Collider and recorded by the ATLAS detector from 2015 to 2018, and corresponds to an integrated luminosity of 139 fb−1. The observed data are compatible with the expected Standard Model background. Results are interpreted in a simplified model where each bottom squark is assumed to decay into the second-lightest neutralino ˜χ02 and a bottom quark, with ˜χ02 decaying into a Higgs boson and the lightest neutralino ˜χ01. The search focuses on final states where at least one Higgs boson decays into a pair of hadronically decaying τ-leptons. This allows the acceptance and thus the sensitivity to be significantly improved relative to the previous results at low masses of the ˜χ02, where bottom-squark masses up to 850 GeV are excluded at the 95% confidence level, assuming a mass difference of 130 GeV between ˜χ02 and ˜χ01. Model-independent upper limits are also set on the cross section of processes beyond the Standard Model

Search for squarks and gluinos in final states with one isolated lepton, jets, and missing transverse momentum at √s=13 TeV with the ATLAS detector

The results of a search for gluino and squark pair production with the pairs decaying via the lightest charginos into a final state consisting of two W bosons, the lightest neutralinos (χ˜ 01 ), and quarks, are presented: the signal is characterised by the presence of a single charged lepton (e± or μ±) from a W boson decay, jets, and missing transverse momentum. The analysis is performed using 139 fb−1 of proton–proton collision data taken at a centre-of-mass energy √s = 13 delivered by the Large Hadron Collider and recorded by the ATLAS experiment. No statistically significant excess of events above the Standard Model expectation is found. Limits are set on the direct production of squarks and gluinos in simplified models. Masses of gluino (squark) up to 2.2 (1.4 ) are excluded at 95% confidence level for a light χ˜ 01

A search for the decays of stopped long-lived particles at √ s= 13 TeV with the ATLAS detector

A search for long-lived particles, which have come to rest within the ATLAS detector, is presented. The subsequent decays of these particles can produce high-momentum jets, resulting in large out-of-time energy deposits in the ATLAS calorimeters. These de- cays are detected using data collected during periods in the LHC bunch structure when collisions are absent. The analysed dataset is composed of events from proton-proton collisions produced by the Large Hadron Collider at a centre-of-mass energy of √ s= 13 TeV and recorded by the ATLAS experiment during 2017 and 2018. The dataset used for this search corresponds to a total live time of 579 hours. The results of this search are used to derive lower limits on the mass of gluino R-hadrons, assuming a branching fraction B(g∼→qq¯¯χ01) = 100%, with masses of up to 1.4 TeV excluded for gluino lifetimes of 10−5 to 103 s

Search for dark matter produced in association with a Standard Model Higgs boson decaying into b-quarks using the full Run 2 dataset from the ATLAS detector

The production of dark matter in association with Higgs bosons is predicted in several extensions of the Standard Model. An exploration of such scenarios is presented, considering final states with missing transverse momentum and b-tagged jets consistent with a Higgs boson. The analysis uses proton-proton collision data at a centre-of-mass energy of 13 TeV recorded by the ATLAS experiment at the LHC during Run 2, amounting to an integrated luminosity of 139 fb−1. The analysis, when compared with previous searches, benefits from a larger dataset, but also has further improvements providing sensitivity to a wider spectrum of signal scenarios. These improvements include both an optimised event selection and advances in the object identification, such as the use of the likelihood-based significance of the missing transverse momentum and variable-radius track-jets. No significant deviation from Standard Model expectations is observed. Limits are set, at 95% confidence level, in two benchmark models with two Higgs doublets extended by either a heavy vector boson Z0 or a pseudoscalar singlet a and which both provide a dark matter candidate χ. In the case of the two-Higgs-doublet model with an additional vector boson Z0, the observed limits extend up to a Z0 mass of 3 TeV for a mass of 100 GeV for the dark matter candidate. The two-Higgs-doublet model with a dark matter particle mass of 10 GeV and an additional pseudoscalar a is excluded for masses of the a up to 520 GeV and 240 GeV for tan β = 1 and tan β = 10 respectively. Limits on the visible cross-sections are set and range from to 0.05 fb to 3.26 fb, depending on the missing transverse momentum and b-quark jet multiplicity requirements

Search for Lepton-Flavor Violation in Z-Boson Decays with τ Leptons with the ATLAS Detector

A search for lepton-flavor-violating Z→eτ and Z→μτ decays with pp collision data recorded by the ATLAS detector at the LHC is presented. This analysis uses 139 fb−1 of Run 2 pp collisions at √s=13 TeV and is combined with the results of a similar ATLAS search in the final state in which the τ lepton decays hadronically, using the same data set as well as Run 1 data. The addition of leptonically decaying τ leptons significantly improves the sensitivity reach for Z→ℓτ decays. The Z→ℓτ branching fractions are constrained in this analysis to B(Z→eτ)<7.0×10−6 and B(Z→μτ)<7.2×10−6 at 95% confidence level. The combination with the previously published analyses sets the strongest constraints to date: B(Z→eτ)<5.0×10−6 and B(Z→μτ)<6.5×10−6 at 95% confidence level