Executive Summary:International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients’ readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of &gt;80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of &gt;80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.</p

Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A PALISI Network Document

RATIONALE: Pediatric specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients' readiness for extubation. METHODS: Twenty-six international experts comprised a multi-professional panel to establish pediatric specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. Systematic review was conducted for questions which did not meet an a-priori threshold of ≥80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence, drafted, and voted on the recommendations. MEASUREMENTS AND MAIN RESULTS: Three questions related to systematic screening, using an extubation readiness testing bundle and use of a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ≥80% agreement. For the remaining 8 questions, 5 systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials; measures of respiratory muscle strength; assessment of risk of post-extubation upper airway obstruction and its prevention; use of post-extubation non-invasive respiratory support; and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. CONCLUSION: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.The project was funded by Eunice Kennedy Shriver National Institute of Child Health (NICHD) and Human Development National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (R13HD102137), in addition to funds from department of pediatrics at Indiana University School of Medicine, Indianapolis, Indiana

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Observation and branching fraction measurement of the decay Ξb−→Λb0π−\Xi_b^-\to\Lambda_b^0\pi^-

International audienceThe decay $\Xi_b^-\to\Lambda_b^0\pi^-$ is observed using a proton-proton collision data sample collected at center-of-mass energy $\sqrt{s}=13$ TeV with the LHCb detector, corresponding to an integrated luminosity of 5.5 fb$^{-1}$. This process is mediated by the $s\to u\bar{u}d$ quark-level transition, where the $b$ quark in the $\Xi_b^-$ baryon is a spectator in the decay. Averaging the results obtained using the two $\Lambda_b^0$ decay modes, $\Lambda_b^0\to\Lambda_c^+\pi^-$ and $\Lambda_b^0\to\Lambda_c^+\pi^-\pi^+\pi^-$, the relative production ratio is measured to be $(f_{\Xi_b^-}/f_{\Lambda_b^0}){\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)=(7.3\pm0.8\pm0.6)\times10^{-4}$. Here the uncertainties are statistical and systematic, respectively, and $f_{\Xi_b^-}(f_{\Lambda_b^0})$ is the fragmentation fraction for a $b$ quark into a $\Xi_b^-$ ($\Lambda_b^0$) baryon. Using an independent measurement of $f_{\Xi_b^-}/f_{\Lambda_b^0}$, the branching fraction ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)=(0.89\pm0.10\pm0.07\pm0.29)\%$ is obtained, where the last uncertainty is due to the assumed SU(3) flavor symmetry in the determination of $f_{\Xi_b^-}/f_{\Lambda_b^0}$

Observation of the decays B(s)0→Ds1(2536)∓K±B_{(s)}^{0}\to D_{s1}(2536)^{\mp}K^{\pm}

International audienceThis paper reports the observation of the decays $B_{(s)}^{0}\to D_{s1}(2536)^{\mp}K^{\pm}$ using proton-proton collision data collected by the LHCb experiment, corresponding to an integrated luminosity of $9\,\mathrm{fb}^{-1}$. The branching fractions of these decays are measured relative to the normalisation channel $B^{0}\to \overline{D}^{0}K^{+}K^{-}$. The $D_{s1}(2536)^{-}$ meson is reconstructed in the $\overline{D}^{*}(2007)^{0}K^{-}$ decay channel and the products of branching fractions are measured to be $$\mathcal{B}(B_{s}^{0}\to D_{s1}(2536)^{\mp}K^{\pm})\times\mathcal{B}(D_{s1}(2536)^{-}\to\overline{D}^{*}(2007)^{0}K^{-})=(2.49\pm0.11\pm0.12\pm0.25\pm0.06)\times 10^{-5},$$$$\mathcal{B}(B^{0}\to D_{s1}(2536)^{\mp}K^{\pm})\times\mathcal{B}(D_{s1}(2536)^{-}\to\overline{D}^{*}(2007)^{0}K^{-}) = (0.510\pm0.021\pm0.036\pm0.050)\times 10^{-5}.$$ The first uncertainty is statistical, the second systematic, and the third arises from the uncertainty of the branching fraction of the $B^{0}\to \overline{D}^{0}K^{+}K^{-}$ normalisation channel. The last uncertainty in the $B_{s}^{0}$ result is due to the limited knowledge of the fragmentation fraction ratio, $f_{s}/f_{d}$. The significance for the $B_{s}^{0}$ and $B^{0}$ signals is larger than $10\,\sigma$. The ratio of the helicity amplitudes which governs the angular distribution of the $D_{s1}(2536)^{-}\to\overline{D}^{*}(2007)^{0}K^{-}$ decay is determined from the data. The ratio of the $S$- and $D$-wave amplitudes is found to be $1.11\pm0.15\pm 0.06$ and its phase $0.70\pm0.09\pm 0.04$ rad, where the first uncertainty is statistical and the second systematic

Measurement of CP violation in B0→ψ(→ℓ+ℓ−)KS0(→π+π−)B^0\to\psi(\to\ell^+\ell^-)K^0_S(\to\pi^+\pi^-) decays

International audienceA measurement of time-dependent CP violation in the decays of $B^0$ and $\overline{B}^0$ mesons to the final states $J/\psi(\to\mu^+\mu^-)K^0_S$, $\psi(2S)(\to\mu^+\mu^-)K^0_S$ and $J/\psi(\to e^+e^-)K^0_S$ with $K^0_S\to\pi^+\pi^-$ is presented. The data correspond to an integrated luminosity of 6 fb${}^{-1}$ collected at a centre-of-mass energy of $\sqrt{s}=13$ TeV with the LHCb detector. The CP-violation parameters are measured to be \begin{align*} S_{\psi K^0_S} &= 0.717 \pm 0.013 (\text{stat}) \pm 0.008 (\text{syst}), \\ C_{\psi K^0_S} &= 0.008 \pm 0.012 (\text{stat}) \pm 0.003 (\text{syst}). \end{align*} This measurement of $S_{\psi K^0_S}$ represents the most precise single measurement of the CKM angle $\beta$ to date and is more precise than the current world average. In addition, measurements of the CP-violation parameters of the individual channels are reported and a combination with the LHCb Run 1 measurements is performed

Measurement of the CKM angle γ\gamma using the B±→D∗h±B^{\pm}\rightarrow D^{*} h^{\pm} channels

International audienceA measurement of the $CP$-violating observables from $B^{\pm}\rightarrow D^* K^{\pm}$ and $B^{\pm}\rightarrow D^* \pi^{\pm}$ decays is presented, where $D^* (D)$ is an admixture of $D^{*0}$ and $\bar{D}^{*0}$ ($D^0$ and $\bar{D}^0$) states and is reconstructed through the decay chains $D^* \rightarrow D\pi^0/\gamma$ and $D \to K_S^0 \pi^+\pi^-/K_S^0 K^+K^-$. The measurement is performed by analysing the signal yield variation across the $D$ decay phase space and is independent of any amplitude model. The data sample used was collected by the LHCb experiment in proton-proton collisions and corresponds to a total integrated luminosity of 9 fb$^{-1}$ at centre-of-mass energies of 7, 8 and 13 TeV. The CKM angle $\gamma$ is determined to be $(69^{+13}_{-14})^{\circ}$ using the measured $CP$-violating observables. The hadronic parameters $r^{D^* K^{\pm}}_B, r^{D^* \pi^{\pm}}_B, \delta^{D^* K^{\pm}}_B, \delta^{D^* \pi^{\pm}}_B$, which are the ratios and strong phase differences between favoured and suppressed $B^{\pm}$ decays, are also reported

Freeze-out radii extracted from three-pion cumulants in pp, p–Pb and Pb–Pb collisions at the LHC

In high-energy collisions, the spatio-temporal size of the particle production region can be measured using the Bose–Einstein correlations of identical bosons at low relative momentum. The source radii are typically extracted using two-pion correlations, and characterize the system at the last stage of interaction, called kinetic freeze-out. In low-multiplicity collisions, unlike in high-multiplicity collisions, two-pion correlations are substantially altered by background correlations, e.g. mini-jets. Such correlations can be suppressed using three-pion cumulant correlations. We present the first measurements of the size of the system at freeze-out extracted from three-pion cumulant correlations in pp, p–Pb and Pb–Pb collisions at the LHC with ALICE. At similar multiplicity, the invariant radii extracted in p–Pb collisions are found to be 5–15% larger than those in pp, while those in Pb–Pb are 35–55% larger than those in p–Pb. Our measurements disfavor models which incorporate substantially stronger collective expansion in p–Pb as compared to pp collisions at similar multiplicity

Freeze-out radii extracted from three-pion cumulants in pp, p–Pb and Pb–Pb collisions at the LHC

In high-energy collisions, the spatio-temporal size of the particle production region can be measured using the Bose-Einstein correlations of identical bosons at low relative momentum. The source radii are typically extracted using two-pion correlations, and characterize the system at the last stage of interaction, called kinetic freeze-out. In low-multiplicity collisions, unlike in high-multiplicity collisions, two-pion correlations are substantially altered by background correlations, e.g. mini-jets. Such correlations can be suppressed using three-pion cumulant correlations. We present the first measurements of the size of the system at freeze-out extracted from three-pion cumulant correlations in pp, p-Pb and Pb-Pb collisions at the LHC with ALICE. At similar multiplicity, the invariant radii extracted in p-Pb collisions are found to be 5-15% larger than those in pp, while those in Pb-Pb are 35-55% larger than those in p-Pb. Our measurements disfavor models which incorporate substantially stronger collective expansion in p-Pb as compared to pp collisions at similar multiplicity