Using machine learning to predict antibody response to SARS-CoV-2 vaccination in solid organ transplant recipients: the multicentre ORCHESTRA cohort

Objectives: Study aim is to assess predictors of negative antibody response (AbR) in solid organ transplant (SOT) recipients after the first booster of SARS-CoV-2 vaccination. Methods: SOT recipients receiving SARS-CoV-2 vaccination were prospectively enrolled (March 2021-January 2022) at six hospitals in Italy and Spain. AbR was assessed at first dose (t0), second dose (t1), 3±1 month (t2), and 1 month after third dose (t3). Negative AbR at t3 was defined as anti-receptor binding domain titre <45 BAU/mL. Machine Learning models were developed to predict the individual risk of negative (vs. positive) AbR using as covariates age, type of transplant, time between transplant and vaccination, immunosuppressive drugs, type of vaccine, and graft function, and subsequently assessed using a validation cohort. Results: Overall, 1615 SOT recipients (1072 [66.3%] males, mean±standard deviation (SD) age 57.85±13.77) were enrolled and 1211 received three vaccination doses. Negative AbR rate decreased from (886/946) 93.66% to (202/923) 21.90% from t0 to t3. Univariate analysis showed that older patients (mean age 60.21±11.51 vs. 58.11±13.08), anti-metabolites (57.9% vs. 35.1%) steroids (52.9% vs. 38.5%), recent transplantation (<3 years) (17.8% vs. 2.3%), and kidney, heart, or lung compared to liver transplantation (25%, 31.8%, 30.4% vs. 5.5%) had a higher likelihood of negative AbR. Machine learning algorithms showing best prediction performance were logistic regression (precision recall curve-PRAUC mean 0.37 [95%CI 0.36-0.39]) and k-Nearest Neighbors (PRAUC 0.36 [0.35-0.37]). Conclusions: Almost a quarter of SOT recipients showed negative AbR after first booster dosage. Unfortunately, clinical information cannot efficiently predict negative AbR even with ML algorithms

Phi and Omega meson production in anti-p p annihilation and the OZI rule

The ~b~r+/toTr + ratio from hp annihilations on a liquid hydrogen target, for h momenta between 64 and 297 MeV/c, was measured using the OBELIX spectrometer at LEAR. The raUo R(dpTr/torr) = tr(~p --~ dp~r+)/tr(hp ~ tour +) turned out 0.110 + 0.015star 4- 0.006syst. Implications of this result on the OZI rule are discussed

Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.

BackgroundBaricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.MethodsIn this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168.FindingsBetween Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012).InterpretationIn hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered.FundingNational Institute of Allergy and Infectious Diseases

Observation of B-s(0) -> chi(c1)phi decay and study of B-0 -> chi K-c1,K-2*(0) decays

The first observation of the decay B-s(0) -> chi(c1)phi and a study of B-0 -> chi K-c1,K-2*(0) decays are presented. The analysis is performed using a dataset, corresponding to an integrated luminosity of 1.0 fb(-1), collected by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. The following ratios of branching fractions are measured: B(B-s(0) -> chi(c1)phi)/B(B-s(0) -> J/psi phi) = (18.9 +/- 1.8 (stat) +/- 1.3 (syst) +/- 0.8(B)) x 10(-2), B(B-0 -> chi K-c1*(0))//B(B-0 -> J/psi K*(0)) = (19.8 +/- 1.1 (stat) +/- 1.2 (syst) +/- 0.9(B)) x 10(-2), B(B-0 -> chi K-c2*(0))//B(B-0 -> chi K-c1*(0)) = (17.1 +/- 5.0 (stat) +/- 1.7 (syst) +/- 1.1(B)) x 10(-2), where the third uncertainty is due to the limited knowledge of the branching fractions of chi(c) -> J/psi gamma modes

Measurement of the flavour-specific CP-violating asymmetry a(sl)(s) in B-s(0) decays

The CP-violating asymmetry a(sl)(s), is studied using semileptonic decays of B-s(0) and (B) over bar (0)(s) mesons produced in pp collisions at a centre-of-mass energy of 7 TeV at the LHC, exploiting a data sample corresponding to an integrated luminosity of 1.0 fb(-1). The reconstructed final states are D-s(+/-)mu(+/-)(s), with the D-s(+/-) particle decaying in the phi pi(+/-) mode. The D-s(+/-)mu(+/-)(s) yields are summed over B-s(0) and (B) over bar (0)(s) initial states, and integrated with respect to decay time. Data-driven methods are used to measure efficiency ratios. We obtain a(sl)(s) = (-0.06 +/- 0.50 +/- 0.36)%, where the first uncertainty is statistical and the second systematic

First measurement of time-dependent CP violation in Bs0→K+K− B_s^0\to K^+K^- decays

Direct and mixing-induced CP-violating asymmetries in B-s(0) -> K+K- decays are measured for the first time using a data sample of p p collisions, corresponding to an integrated luminosity of 1.0 fb(-1), collected with the LHCb detector at a centre-of-mass energy of 7 TeV. The results are C-KK = 0.14 +/- 0.11 +/- 0.03 and S-KK = 0.30 +/- 0.12 +/- 0.04, where the first uncertainties are statistical and the second systematic. The corresponding quantities are also determined for B-0 -> pi(+)pi(-) decays to be C-pi pi = -0.38 +/- 0.15 +/- 0.02 and S-pi pi = -0.71 +/- 0.13 +/- 0.02, in good agreement with existing measurements

Search for the rare decay D-0 -> mu(+) mu(-)

A search for the rare decay D-0 -> mu(+) mu(-) is performed using a data sample, corresponding to an integrated luminosity of 0.9 fb(-1), of pp collisions collected at a centre-of-mass energy of 7 TeV by the LHCb experiment. The observed number of events is consistent with the background expectations and corresponds to an upper limit of B(D-0 -> mu(+) mu(-)) < 6.2 (7.6) x 10(-9) at 90% (95%) confidence level. This result represents an improvement of more than a factor twenty with respect to previous measurements

Study of the rare B-s(0) and B-0 decays into the pi(+) pi(-) mu(+) mu(-) final state

A search for the rare decays B-s(0) -> pi(+) pi-mu(+) mu-and B-0 -> pi(+) pi-mu(+) mu-is performed in a data set corresponding to an integrated luminosity of 3.0 fb(-1) collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3GeV/c(2) and with muon pairs that do not originate from a resonance are considered. The first observation of the decay B-s(0) -> pi(+) pi-mu(+) mu- and the first evidence of the decay B-0 -> pi(+) pi-mu(+) mu-are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be B(B-s(0) -> pi(+) pi-mu(+) mu(-)) =(8.6 +/- 1.5(stat) +/- 0.7(syst) +/- 0.7 (norm)) x 10(-8) and B(B-0 -> pi(+) pi-mu(+) mu(-)) =(2.11 +/- 0.51(stat) +/- 0.15(syst) +/- 0.16(norm)) x10(-8), where the third uncertainty is due to the branching fraction of the decay B-0. -> J/Psi(mu(+) mu(-)) K*(892)(0)(-> K+ pi(-)), used as a normalisation. (C) 2015 The Authors. Published by Elsevier B.V

Identification of beauty and charm quark jets at LHCb

Identification of jets originating from beauty and charm quarks is important for measuring Standard Model processes and for searching for new physics. The performance of algorithms developed to select b- and c-quark jets is measured using data recorded by LHCb from proton-proton collisions at root s = 7TeV in 2011 and at root s = 8TeV in 2012. The efficiency for identifying a b (c) jet is about 65%(25%) with a probability for misidentifying a light-parton jet of 0.3% for jets with transverse momentum pT > 20GeV and pseudorapidity 2 : 2 < eta < 4.2. The dependence of the performance on the pT and eta of the jet is also measured

Measurement of the CP-violating phase beta in B-0 -> J/psi pi(+)pi(-) decays and limits on penguin effects

Time-dependent CP violation is measured in the (B-0) over bar -> J/psi pi(+)pi(-) p-channel for each pi(+)pi(-) resonant final state using data collected with an integrated luminosity of 3.0 fb(-1) in pp collisions using the LHCb detector. The final state with the largest rate, J/psi rho(0)(770), is used to measure the CP-violating angle 2 beta(eff) to be (41.7 +/- 9.6(-6.3)(+2.8)).. This result can be used to limit the size of penguin amplitude contributions to CPviolation measurements in, for example, (B-0) over bar -> J/psi pi(+)pi(-) decays. Assuming approximate SU(3) flavour symmetry and neglecting higher order diagrams, the shift in the CP-violating phase phi(s) limited to be within the interval [-1.05 degrees, + 1.18 degrees] at 95% confidence level. Changes to the limit due to SU(3) symmetry breaking effects are also discussed. (C) 2015 The Authors. Published by Elsevier B.V