Characterization of Domiphen Bromide as a New Fast-Acting Antiplasmodial Agent Inhibiting the Apicoplastidic Methyl Erythritol Phosphate Pathway

The evolution of resistance by the malaria parasite to artemisinin, the key component of the combination therapy strategies that are at the core of current antimalarial treatments, calls for the urgent identification of new fast-acting antimalarials. The apicoplast organelle is a preferred target of antimalarial drugs because it contains biochemical processes absent from the human host. Fosmidomycin is the only drug in clinical trials targeting the apicoplast, where it inhibits the methyl erythritol phosphate (MEP) pathway. Here, we characterized the antiplasmodial activity of domiphen bromide (DB), another MEP pathway inhibitor with a rapid mode of action that arrests the in vitro growth of Plasmodium falciparum at the early trophozoite stage. Metabolomic analysis of the MEP pathway and Krebs cycle intermediates in 20 mu M DB-treated parasites suggested a rapid activation of glycolysis with a concomitant decrease in mitochondrial activity, consistent with a rapid killing of the pathogen. These results present DB as a model compound for the development of new, potentially interesting drugs for future antimalarial combination therapies

National critical incident reporting systems relevant to anaesthesia: a European survey

Background Critical incident reporting is a key tool in the promotion of patient safety in anaesthesia. Methods We surveyed representatives of national incident reporting systems in six European countries, inviting information on scope and organization, and intelligence on factors determining success and failure. Results Some systems are government-run and nationally conceived; others started out as small, specialty-focused initiatives, which have since acquired a national reach. However, both national co-ordination and specialty enthusiasts seem to be necessary for an optimally functioning system. The role of reporting culture, definitional issues, and dissemination is discussed. Conclusions We make recommendations for others intending to start new systems and speculate on the prospects for sharing patient safety lessons relevant to anaesthesia at European leve

Measurement of the Bs0→J/ψηB_{s}^{0} \rightarrow J/\psi \eta lifetime

Using a data set corresponding to an integrated luminosity of $3 fb^{-1}$, collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of 7 and 8 TeV, the effective lifetime in the $B^0_s \rightarrow J/\psi \eta$ decay mode, $\tau_{\textrm{eff}}$, is measured to be $\tau_{\textrm{eff}} = 1.479 \pm 0.034~\textrm{(stat)} \pm 0.011 ~\textrm{(syst)}$ ps. Assuming $CP$ conservation, $\tau_{\textrm{eff}}$ corresponds to the lifetime of the light $B_s^0$ mass eigenstate. This is the first measurement of the effective lifetime in this decay mode.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-017.htm

Model-independent evidence for J/ψpJ/\psi p contributions to Λb0→J/ψpK−\Lambda_b^0\to J/\psi p K^- decays

The data sample of $\Lambda_b^0\to J/\psi p K^-$ decays acquired with the LHCb detector from 7 and 8~TeV $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$, is inspected for the presence of $J/\psi p$ or $J/\psi K^-$ contributions with minimal assumptions about $K^- p$ contributions. It is demonstrated at more than 9 standard deviations that $\Lambda_b^0\to J/\psi p K^-$ decays cannot be described with $K^- p$ contributions alone, and that $J/\psi p$ contributions play a dominant role in this incompatibility. These model-independent results support the previously obtained model-dependent evidence for $P_c^+\to J/\psi p$ charmonium-pentaquark states in the same data sample.Comment: 21 pages, 12 figures (including the supplemental section added at the end

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date

Bose-Einstein correlations of same-sign charged pions in the forward region in pp collisions at √s=7 TeV

Bose-Einstein correlations of same-sign charged pions, produced in protonproton collisions at a 7 TeV centre-of-mass energy, are studied using a data sample collected by the LHCb experiment. The signature for Bose-Einstein correlations is observed in the form of an enhancement of pairs of like-sign charged pions with small four-momentum difference squared. The charged-particle multiplicity dependence of the Bose-Einstein correlation parameters describing the correlation strength and the size of the emitting source is investigated, determining both the correlation radius and the chaoticity parameter. The measured correlation radius is found to increase as a function of increasing charged-particle multiplicity, while the chaoticity parameter is seen to decreas

Amplitude analysis of B+→J/ψϕK+B^+\to J/\psi \phi K^+ decays

The first full amplitude analysis of $B^+\to J/\psi \phi K^+$ with $J/\psi\to\mu^+\mu^-$, $\phi\to K^+K^-$ decays is performed with a data sample of 3 fb$^{-1}$ of $pp$ collision data collected at $\sqrt{s}=7$ and $8$ TeV with the LHCb detector. The data cannot be described by a model that contains only excited kaon states decaying into $\phi K^+$, and four $J/\psi\phi$ structures are observed, each with significance over $5$ standard deviations. The quantum numbers of these structures are determined with significance of at least $4$ standard deviations. The lightest has mass consistent with, but width much larger than, previous measurements of the claimed $X(4140)$ state. The model includes significant contributions from a number of expected kaon excitations, including the first observation of the $K^{*}(1680)^+\to\phi K^+$ transition.Comment: 62 pages 26 figure

Observation of J/ψϕJ/\psi\phi structures consistent with exotic states from amplitude analysis of B+→J/ψϕK+B^+\to J/\psi \phi K^+ decays

The first full amplitude analysis of $B^+\to J/\psi \phi K^+$ with $J/\psi\to\mu^+\mu^-$, $\phi\to K^+K^-$ decays is performed with a data sample of 3 fb$^{-1}$ of $pp$ collision data collected at $\sqrt{s}=7$ and $8$ TeV with the LHCb detector. The data cannot be described by a model that contains only excited kaon states decaying into $\phi K^+$, and four $J/\psi\phi$ structures are observed, each with significance over $5$ standard deviations. The quantum numbers of these structures are determined with significance of at least $4$ standard deviations. The lightest has mass consistent with, but width much larger than, previous measurements of the claimed $X(4140)$ state.Comment: 17 pages, 3 figure

Study of J /ψ production in Jets

The production of J/ψ mesons in jets is studied in the forward region of proton-proton collisions using data collected with the LHCb detector at a center-of-mass energy of 13 TeV. The fraction of the jet transverse momentum carried by the J/ψ meson, z(J/ψ)≡pT(J/ψ)/pT(jet), is measured using jets with pT(jet)>20 GeV in the pseudorapidity range 2.5<η(jet)<4.0. The observed z(J/ψ)distribution for J/ψ mesons produced in b-hadron decays is consistent with expectations. However, the results for prompt J/ψ production do not agree with predictions based on fixed-order nonrelativistic QCD. This is the first measurement of the pT fraction carried by prompt J/ψ mesons in jets at any experiment