Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Measurement of CP violation parameters and polarisation fractions in Bs0→J/ψK‾∗0 {\mathrm{B}}_{\mathrm{s}}^0\to \mathrm{J}/\psi {\overline{\mathrm{K}}}^{\ast 0} decays

The first measurement of ${C\!P}$ asymmetries in the decay ${B_s^0\to J/\psi \overline{K}^{*}(892)^{0}}$ and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of $3.0\,fb^{-1}$ of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of $7$ and $8\,\mathrm{TeV}$. Together with constraints from ${B^0\to J/\psi \rho^0}$, the results are used to constrain additional contributions due to penguin diagrams in the ${C\!P}$-violating phase ${{\phi}_{s}}$, measured through ${B_s^0}$ decays to charmonium.The first measurement of CP asymmetries in the decay ${B}_s^0\to J/\psi {\overline{\mathrm{K}}}^{\ast }{(892)}^0$ and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of 3.0 fb^{−}^{1} of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Together with constraints from B$^{0}$ → J/ψ ρ$^{0}$, the results are used to constrain additional contributions due to penguin diagrams in the CP -violating phase ϕ$_{s}$ , measured through B$_{s}^{0}$ decays to charmonium.The first measurement of ${C\!P}$ asymmetries in the decay ${B_s^0\to J/\psi \overline{K}^{*}(892)^{0}}$ and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of $3.0\,fb^{-1}$ of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of $7$ and $8\,\mathrm{TeV}$. Together with constraints from ${B^0\to J/\psi \rho^0}$, the results are used to constrain additional contributions due to penguin diagrams in the ${C\!P}$-violating phase ${{\phi}_{s}}$, measured through ${B_s^0}$ decays to charmonium

Measurement of the J/ψ pair production cross-section in pp collisions at s=13 \sqrt{s}=13 TeV

The production cross-section of J/ψ pairs is measured using a data sample of pp collisions collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=13$ TeV, corresponding to an integrated luminosity of 279 ±11 pb$^{−1}$. The measurement is performed for J/ψ mesons with a transverse momentum of less than 10 GeV/c in the rapidity range 2.0 < y < 4.5. The production cross-section is measured to be 15.2 ± 1.0 ± 0.9 nb. The first uncertainty is statistical, and the second is systematic. The differential cross-sections as functions of several kinematic variables of the J/ψ pair are measured and compared to theoretical predictions.The production cross-section of $J/\psi$ pairs is measured using a data sample of $pp$ collisions collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s} = 13 \,{\mathrm{TeV}}$, corresponding to an integrated luminosity of $279 \pm 11 \,{\mathrm{pb^{-1}}}$. The measurement is performed for $J/\psi$ mesons with a transverse momentum of less than $10 \,{\mathrm{GeV}}/c$ in the rapidity range $2.0<y<4.5$. The production cross-section is measured to be $15.2 \pm 1.0 \pm 0.9 \,{\mathrm{nb}}$. The first uncertainty is statistical, and the second is systematic. The differential cross-sections as functions of several kinematic variables of the $J/\psi$ pair are measured and compared to theoretical predictions

Measurement of forward W→eνW\to e\nu production in pppp collisions at s=8 \sqrt{s}=8\,TeV

A measurement of the cross-section for $W \to e\nu$ production in $pp$ collisions is presented using data corresponding to an integrated luminosity of $2\,$fb$^{-1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8\,$TeV. The electrons are required to have more than $20\,$GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive $W$ production cross-sections, where the $W$ decays to $e\nu$, are measured to be \begin{align*} \begin{split} \sigma_{W^{+} \to e^{+}\nu_{e}}&=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\,\mathrm{pb},\\ \sigma_{W^{-} \to e^{-}\bar{\nu}_{e}}&=\,\,\,809.0\pm 1.9\pm 18.1\pm\,\,\,7.0\pm \phantom{0}9.4\,\mathrm{pb}, \end{split} \end{align*} where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination. Differential cross-sections as a function of the electron pseudorapidity are measured. The $W^{+}/W^{-}$ cross-section ratio and production charge asymmetry are also reported. Results are compared with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics. Finally, in a precise test of lepton universality, the ratio of $W$ boson branching fractions is determined to be \begin{align*} \begin{split} \mathcal{B}(W \to e\nu)/\mathcal{B}(W \to \mu\nu)=1.020\pm 0.002\pm 0.019, \end{split} \end{align*} where the first uncertainty is statistical and the second is systematic.A measurement of the cross-section for $W \to e\nu$ production in $pp$ collisions is presented using data corresponding to an integrated luminosity of $2\,$fb$^{-1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8\,$TeV. The electrons are required to have more than $20\,$GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive $W$ production cross-sections, where the $W$ decays to $e\nu$, are measured to be \begin{equation*} \sigma_{W^{+} \to e^{+}\nu_{e}}=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\,\mathrm{pb}, \end{equation*} \begin{equation*} \sigma_{W^{-} \to e^{-}\bar{\nu}_{e}}=\,\,\,809.0\pm 1.9\pm 18.1\pm\,\,\,7.0\pm \phantom{0}9.4\,\mathrm{pb}, \end{equation*} where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination. Differential cross-sections as a function of the electron pseudorapidity are measured. The $W^{+}/W^{-}$ cross-section ratio and production charge asymmetry are also reported. Results are compared with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics. Finally, in a precise test of lepton universality, the ratio of $W$ boson branching fractions is determined to be \begin{equation*} \mathcal{B}(W \to e\nu)/\mathcal{B}(W \to \mu\nu)=1.020\pm 0.002\pm 0.019, \end{equation*} where the first uncertainty is statistical and the second is systematic.A measurement of the cross-section for W → eν production in pp collisions is presented using data corresponding to an integrated luminosity of 2 fb$^{−1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8$ TeV. The electrons are required to have more than 20 GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive W production cross-sections, where the W decays to eν, are measured to be ${\sigma}_{W^{+}\to {e}^{+}{\nu}_e}=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\kern0.5em \mathrm{p}\mathrm{b},$ ${\sigma}_{W^{-}\to {e}^{-}{\overline{\nu}}_e}=809.0\pm 1.9\pm 18.1\pm \kern0.5em 7.0\pm \kern0.5em 9.4\,\mathrm{p}\mathrm{b},$ where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination

Measurement of the B0s→μ+μ− Branching Fraction and Effective Lifetime and Search for B0→μ+μ− Decays

A search for the rare decays Bs0→μ+μ- and B0→μ+μ- is performed at the LHCb experiment using data collected in pp collisions corresponding to a total integrated luminosity of 4.4  fb-1. An excess of Bs0→μ+μ- decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be B(Bs0→μ+μ-)=(3.0±0.6-0.2+0.3)×10-9, where the first uncertainty is statistical and the second systematic. The first measurement of the Bs0→μ+μ- effective lifetime, τ(Bs0→μ+μ-)=2.04±0.44±0.05  ps, is reported. No significant excess of B0→μ+μ- decays is found, and a 95% confidence level upper limit, B(B0→μ+μ-)<3.4×10-10, is determined. All results are in agreement with the standard model expectations.A search for the rare decays $B^0_s\to\mu^+\mu^-$ and $B^0\to\mu^+\mu^-$ is performed at the LHCb experiment using data collected in $pp$ collisions corresponding to a total integrated luminosity of 4.4 fb$^{-1}$. An excess of $B^0_s\to\mu^+\mu^-$ decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be ${\cal B}(B^0_s\to\mu^+\mu^-)=\left(3.0\pm 0.6^{+0.3}_{-0.2}\right)\times 10^{-9}$, where the first uncertainty is statistical and the second systematic. The first measurement of the $B^0_s\to\mu^+\mu^-$ effective lifetime, $\tau(B^0_s\to\mu^+\mu^-)=2.04\pm 0.44\pm 0.05$ ps, is reported. No significant excess of $B^0\to\mu^+\mu^-$ decays is found and a 95 % confidence level upper limit, ${\cal B}(B^0\to\mu^+\mu^-)<3.4\times 10^{-10}$, is determined. All results are in agreement with the Standard Model expectations