Showing papers by "Université catholique de Louvain published in 2020"

Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study.

Abstract: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.

PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase.

Abstract: mTORC1 is an important regulator of muscle mass but how it is modulated by oxygen and nutrients is not completely understood. We show that loss of the prolyl hydroxylase domain isoform 1 oxygen sensor in mice (PHD1KO) reduces muscle mass. PHD1KO muscles show impaired mTORC1 activation in response to leucine whereas mTORC1 activation by growth factors or eccentric contractions was preserved. The ability of PHD1 to promote mTORC1 activity is independent of its hydroxylation activity but is caused by decreased protein content of the leucyl tRNA synthetase (LRS) leucine sensor. Mechanistically, PHD1 interacts with and stabilizes LRS. This interaction is promoted during oxygen and amino acid depletion and protects LRS from degradation. Finally, elderly subjects have lower PHD1 levels and LRS activity in muscle from aged versus young human subjects. In conclusion, PHD1 ensures an optimal mTORC1 response to leucine after episodes of metabolic scarcity.

Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia

Abstract: Background Older patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising effica...

The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics

Abstract: In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept. Gut microbiota can be manipulated to benefit host health, including the use of probiotics, prebiotics and synbiotics. This Consensus Statement outlines the definition and scope of the term ‘synbiotics’ as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in May 2019.

GW190814: Gravitational Waves from the Coalescence of a 23 Solar Mass Black Hole with a 2.6 Solar Mass Compact Object

Abstract: We report the observation of a compact binary coalescence involving a 222–243 M ⊙ black hole and a compact object with a mass of 250–267 M ⊙ (all measurements quoted at the 90% credible level) The gravitational-wave signal, GW190814, was observed during LIGO's and Virgo's third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network The source was localized to 185 deg2 at a distance of ${241}_{-45}^{+41}$ Mpc; no electromagnetic counterpart has been confirmed to date The source has the most unequal mass ratio yet measured with gravitational waves, ${0112}_{-0009}^{+0008}$, and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system The dimensionless spin of the primary black hole is tightly constrained to ≤007 Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence We estimate a merger rate density of 1–23 Gpc−3 yr−1 for the new class of binary coalescence sources that GW190814 represents Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models of the formation and mass distribution of compact-object binaries

GW190521: A Binary Black Hole Merger with a Total Mass of 150 M

Abstract: On May 21, 2019 at 03:02:29 UTC Advanced LIGO and Advanced Virgo observed a short duration gravitational-wave signal, GW190521, with a three-detector network signal-to-noise ratio of 14.7, and an estimated false-alarm rate of 1 in 4900 yr using a search sensitive to generic transients. If GW190521 is from a quasicircular binary inspiral, then the detected signal is consistent with the merger of two black holes with masses of 85_{-14}^{+21} M_{⊙} and 66_{-18}^{+17} M_{⊙} (90% credible intervals). We infer that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65 M_{⊙}. We calculate the mass of the remnant to be 142_{-16}^{+28} M_{⊙}, which can be considered an intermediate mass black hole (IMBH). The luminosity distance of the source is 5.3_{-2.6}^{+2.4} Gpc, corresponding to a redshift of 0.82_{-0.34}^{+0.28}. The inferred rate of mergers similar to GW190521 is 0.13_{-0.11}^{+0.30} Gpc^{-3} yr^{-1}.

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer.

Abstract: Background Patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents hav...

Variability in the analysis of a single neuroimaging dataset by many teams

Abstract: Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.

Science Case for the Einstein Telescope

Abstract: The Einstein Telescope (ET), a proposed European ground-based gravitational-wave detector of third-generation, is an evolution of second-generation detectors such as Advanced LIGO, Advanced Virgo, and KAGRA which could be operating in the mid 2030s. ET will explore the universe with gravitational waves up to cosmological distances. We discuss its main scientific objectives and its potential for discoveries in astrophysics, cosmology and fundamental physics.

Mucus barrier, mucins and gut microbiota: the expected slimy partners?

Abstract: The gastrointestinal tract is often considered as a key organ involved in the digestion of food and providing nutrients to the body for proper maintenance. However, this system is composed of organs that are extremely complex. Among the different parts, the intestine is viewed as an incredible surface of contact with the environment and is colonised by hundreds of trillions of gut microbes. The role of the gut barrier has been studied for decades, but the exact mechanisms involved in the protection of the gut barrier are various and complementary. Among them, the integrity of the mucus barrier is one of the first lines of protection of the gastrointestinal tract. In the past, this ‘slimy’ partner was mostly considered a simple lubricant for facilitating the progression of the food bolus and the stools in the gut. Since then, different researchers have made important progress, and currently, the regulation of this mucus barrier is gaining increasing attention from the scientific community. Among the factors influencing the mucus barrier, the microbiome plays a major role in driving mucus changes. Additionally, our dietary habits (ie, high-fat diet, low-fibre/high-fibre diet, food additives, pre- probiotics) influence the mucus at different levels. Given that the mucus layer has been linked with the appearance of diseases, proper knowledge is highly warranted. Here, we debate different aspects of the mucus layer by focusing on its chemical composition, regulation of synthesis and degradation by the microbiota as well as some characteristics of the mucus layer in both physiological and pathological situations.

GW190412: Observation of a binary-black-hole coalescence with asymmetric masses

Abstract: We report the observation of gravitational waves from a binary-black-hole coalescence during the first two weeks of LIGO’s and Virgo’s third observing run. The signal was recorded on April 12, 2019 at 05∶30∶44 UTC with a network signal-to-noise ratio of 19. The binary is different from observations during the first two observing runs most notably due to its asymmetric masses: a ∼30 M⊙ black hole merged with a ∼8 M⊙ black hole companion. The more massive black hole rotated with a dimensionless spin magnitude between 0.22 and 0.60 (90% probability). Asymmetric systems are predicted to emit gravitational waves with stronger contributions from higher multipoles, and indeed we find strong evidence for gravitational radiation beyond the leading quadrupolar order in the observed signal. A suite of tests performed on GW190412 indicates consistency with Einstein’s general theory of relativity. While the mass ratio of this system differs from all previous detections, we show that it is consistent with the population model of stellar binary black holes inferred from the first two observing runs.

Einstein-Gauss-Bonnet Gravity in Four-Dimensional Spacetime.

Abstract: In this Letter we present a general covariant modified theory of gravity in D=4 spacetime dimensions which propagates only the massless graviton and bypasses Lovelock's theorem. The theory we present is formulated in D>4 dimensions and its action consists of the Einstein-Hilbert term with a cosmological constant, and the Gauss-Bonnet term multiplied by a factor 1/(D-4). The four-dimensional theory is defined as the limit D→4. In this singular limit the Gauss-Bonnet invariant gives rise to nontrivial contributions to gravitational dynamics, while preserving the number of graviton degrees of freedom and being free from Ostrogradsky instability. We report several appealing new predictions of this theory, including the corrections to the dispersion relation of cosmological tensor and scalar modes, singularity resolution for spherically symmetric solutions, and others.

Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor.

Abstract: Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.

LOBSTER: Local orbital projections, atomic charges, and chemical-bonding analysis from projector-augmented-wave-based density-functional theory

Abstract: We present an update on recently developed methodology and functionality in the computer program Local Orbital Basis Suite Toward Electronic-Structure Reconstruction (LOBSTER) for chemical-bonding analysis in periodic systems. LOBSTER is based on an analytic projection from projector-augmented wave (PAW) density-functional theory (DFT) computations (Maintz et al., J. Comput. Chem. 2013, 34, 2557), reconstructing chemical information in terms of local, auxiliary atomic orbitals and thereby opening the output of PAW-based DFT codes to chemical interpretation. We demonstrate how LOBSTER has been improved by taking into account time-reversal symmetry, thereby speeding up the DFT and LOBSTER calculations by a factor of 2. Over the recent years, the functionalities have also been continually expanded, including accurate projected densities of states (DOSs), crystal orbital Hamilton population (COHP) analysis, atomic and orbital charges, gross populations, and the recently introduced k-dependent COHP. The software is offered free-of-charge for non-commercial research.

Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis

Abstract: Background In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. Methods In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of Results A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials. Conclusions In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.).

2019 Update of the Joint European League against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis

Abstract: Objective To update the 2012 EULAR/ERA–EDTA recommendations for the management of lupus nephritis (LN). Methods Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. Results The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria 1 g/24 hours despite renin–angiotensin–aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. Conclusions We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.

Properties and Astrophysical Implications of the 150 M Binary Black Hole Merger GW190521

Abstract: The gravitational-wave signal GW190521 is consistent with a binary black hole (BBH) merger source at redshift 0.8 with unusually high component masses, 85-14+21 M o˙ and 66-18+17 M o˙, compared to previously reported events, and shows mild evidence for spin-induced orbital precession. The primary falls in the mass gap predicted by (pulsational) pair-instability supernova theory, in the approximate range 65-120 M o˙. The probability that at least one of the black holes in GW190521 is in that range is 99.0%. The final mass of the merger (142-16+28 M o˙) classifies it as an intermediate-mass black hole. Under the assumption of a quasi-circular BBH coalescence, we detail the physical properties of GW190521's source binary and its post-merger remnant, including component masses and spin vectors. Three different waveform models, as well as direct comparison to numerical solutions of general relativity, yield consistent estimates of these properties. Tests of strong-field general relativity targeting the merger-ringdown stages of the coalescence indicate consistency of the observed signal with theoretical predictions. We estimate the merger rate of similar systems to be 0.13-0.11+0.30 Gpc-3 yr-1. We discuss the astrophysical implications of GW190521 for stellar collapse and for the possible formation of black holes in the pair-instability mass gap through various channels: via (multiple) stellar coalescences, or via hierarchical mergers of lower-mass black holes in star clusters or in active galactic nuclei. We find it to be unlikely that GW190521 is a strongly lensed signal of a lower-mass black hole binary merger. We also discuss more exotic possible sources for GW190521, including a highly eccentric black hole binary, or a primordial black hole binary.

Initial results from the InSight mission on Mars

Abstract: NASA’s InSight (Interior exploration using Seismic Investigations, Geodesy and Heat Transport) mission landed in Elysium Planitia on Mars on 26 November 2018. It aims to determine the interior structure, composition and thermal state of Mars, as well as constrain present-day seismicity and impact cratering rates. Such information is key to understanding the differentiation and subsequent thermal evolution of Mars, and thus the forces that shape the planet’s surface geology and volatile processes. Here we report an overview of the first ten months of geophysical observations by InSight. As of 30 September 2019, 174 seismic events have been recorded by the lander’s seismometer, including over 20 events of moment magnitude Mw = 3–4. The detections thus far are consistent with tectonic origins, with no impact-induced seismicity yet observed, and indicate a seismically active planet. An assessment of these detections suggests that the frequency of global seismic events below approximately Mw = 3 is similar to that of terrestrial intraplate seismic activity, but there are fewer larger quakes; no quakes exceeding Mw = 4 have been observed. The lander’s other instruments—two cameras, atmospheric pressure, temperature and wind sensors, a magnetometer and a radiometer—have yielded much more than the intended supporting data for seismometer noise characterization: magnetic field measurements indicate a local magnetic field that is ten-times stronger than orbital estimates and meteorological measurements reveal a more dynamic atmosphere than expected, hosting baroclinic and gravity waves and convective vortices. With the mission due to last for an entire Martian year or longer, these results will be built on by further measurements by the InSight lander. Geophysical and meteorological measurements by NASA’s InSight lander on Mars reveal a planet that is seismically active and provide information about the interior, surface and atmospheric workings of Mars.

Managing ICU surge during the COVID-19 crisis: rapid guidelines.

Abstract: Given the rapidly changing nature of COVID-19, clinicians and policy makers require urgent review and summary of the literature, and synthesis of evidence-based guidelines to inform practice. The WHO advocates for rapid reviews in these circumstances. The purpose of this rapid guideline is to provide recommendations on the organizational management of intensive care units caring for patients with COVID-19 including: planning a crisis surge response; crisis surge response strategies; triage, supporting families, and staff.

Monocarboxylate transporters in cancer

Abstract: Background Tumors are highly plastic metabolic entities composed of cancer and host cells that can adopt different metabolic phenotypes. For energy production, cancer cells may use 4 main fuels that are shuttled in 5 different metabolic pathways. Glucose fuels glycolysis that can be coupled to the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) in oxidative cancer cells or to lactic fermentation in proliferating and in hypoxic cancer cells. Lipids fuel lipolysis, glutamine fuels glutaminolysis, and lactate fuels the oxidative pathway of lactate, all of which are coupled to the TCA cycle and OXPHOS for energy production. This review focuses on the latter metabolic pathway. Scope of review Lactate, which is prominently produced by glycolytic cells in tumors, was only recently recognized as a major fuel for oxidative cancer cells and as a signaling agent. Its exchanges across membranes are gated by monocarboxylate transporters MCT1-4. This review summarizes the current knowledge about MCT structure, regulation and functions in cancer, with a specific focus on lactate metabolism, lactate-induced angiogenesis and MCT-dependent cancer metastasis. It also describes lactate signaling via cell surface lactate receptor GPR81. Major conclusions Lactate and MCTs, especially MCT1 and MCT4, are important contributors to tumor aggressiveness. Analyses of MCT-deficient (MCT+/- and MCT−/-) animals and (MCT-mutated) humans indicate that they are druggable, with MCT1 inhibitors being in advanced development phase and MCT4 inhibitors still in the discovery phase. Imaging lactate fluxes non-invasively using a lactate tracer for positron emission tomography would further help to identify responders to the treatments.

Extraction and validation of a new set of CMS pythia8 tunes from underlying-event measurements

Abstract: New sets of CMS underlying-event parameters (“tunes”) are presented for the pythia8 event generator. These tunes use the NNPDF3.1 parton distribution functions (PDFs) at leading (LO), next-to-leading (NLO), or next-to-next-to-leading (NNLO) orders in perturbative quantum chromodynamics, and the strong coupling evolution at LO or NLO. Measurements of charged-particle multiplicity and transverse momentum densities at various hadron collision energies are fit simultaneously to determine the parameters of the tunes. Comparisons of the predictions of the new tunes are provided for observables sensitive to the event shapes at LEP, global underlying event, soft multiparton interactions, and double-parton scattering contributions. In addition, comparisons are made for observables measured in various specific processes, such as multijet, Drell–Yan, and top quark-antiquark pair production including jet substructure observables. The simulation of the underlying event provided by the new tunes is interfaced to a higher-order matrix-element calculation. For the first time, predictions from pythia8 obtained with tunes based on NLO or NNLO PDFs are shown to reliably describe minimum-bias and underlying-event data with a similar level of agreement to predictions from tunes using LO PDF sets.

Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study.

Abstract: Summary Background Patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for autologous stem-cell transplantation have poor outcomes and few treatment options. Tafasitamab (MOR208) is an Fc-enhanced, humanised, anti-CD19 monoclonal antibody that has shown preclinical and single-agent activity in patients with relapsed or refractory B-cell malignancies. Preclinical data suggested that tafasitamab might act synergistically with lenalidomide. We aimed to assess the antitumour activity and safety of tafasitamab plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for autologous stem-cell transplantation. Methods In this multicentre, open-label, single-arm, phase 2 study (L-MIND), patients older than 18 years with histologically confirmed diffuse large B-cell lymphoma, who relapsed or had refractory disease after previous treatment with one to three systemic regimens (with at least one anti-CD20 therapy), were not candidates for high-dose chemotherapy and subsequent autologous stem-cell transplantation, had an Eastern Cooperative Oncology Group performance status of 0–2, and had measurable disease at baseline were recruited from 35 academic and community hospitals in ten countries. Patients received coadministered intravenous tafasitamab (12 mg/kg) and oral lenalidomide (25 mg/day) for up to 12 cycles (28 days each), followed by tafasitamab monotherapy (in patients with stable disease or better) until disease progression. The primary endpoint was the proportion of patients with an objective response (centrally assessed), defined as a complete or partial response according to the 2007 International Working Group response criteria for malignant lymphoma. Antitumour activity analyses are based on all patients who received at least one dose of both tafasitamab and lenalidomide; safety analyses are based on all patients who received at least one dose of either study medication. Recruitment is complete, and the trial is in follow-up. This trial is registered with ClinicalTrials.gov , NCT02399085 . Findings Between Jan 18, 2016, and Nov 15, 2017, 156 patients were screened: 81 were enrolled and received at least one dose of either study medication, and 80 received at least one dose of both tafasitamab and lenalidomide. Median follow-up was 13·2 months (IQR 7·3–20·4) as of data cutoff on Nov 30, 2018. 48 (60%; 95% CI 48–71) of 80 patients who received tafasitamab plus lenalidomide had an objective response: 34 (43%; 32–54) had a complete response and 14 (18%; 10–28) had a partial response. The most common treatment-emergent adverse events of grade 3 or worse were neutropenia (39 [48%] of 81 patients), thrombocytopenia (14 [17%]), and febrile neutropenia (ten [12%]). Serious adverse events occurred in 41 (51%) of 81 patients. The most frequently reported serious adverse events (in two or more patients) were pneumonia (five [6%]), febrile neutropenia (five [6%]), pulmonary embolism (three [4%]), bronchitis (two [2%]), atrial fibrillation (two [2%]), and congestive cardiac failure (two [2%]). Interpretation Tafasitamab in combination with lenalidomide was well tolerated and resulted in a high proportion of patients with relapsed or refractory diffuse large B-cell lymphoma ineligible for autologous stem-cell transplantation having a complete response, and might represent a new therapeutic option in this setting. Funding MorphoSys.

Higgs Boson studies at future particle colliders

Abstract: This document aims to provide an assessment of the potential of future colliding beam facilities to perform Higgs boson studies. The analysis builds on the submissions made by the proponents of future colliders to the European Strategy Update process, and takes as its point of departure the results expected at the completion of the HL-LHC program. This report presents quantitative results on many aspects of Higgs physics for future collider projects of sufficient maturity using uniform methodologies.

COVID-19 pandemic and cardiac imaging: EACVI recommendations on precautions, indications, prioritization, and protection for patients and healthcare personnel.

Abstract: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020.