RAPID AND RELIABLE HEALING OF CRITICAL SIZE BONE DEFECTS WITH GENETICALLY MODIFIED SHEEP MUSCLE

Large segmental defects in bone fail to heal and remain a clinical problem. Muscle is highly osteogenic, and preliminary data suggest that autologous muscle tissue expressing bone morphogenetic protein-2 (BMP-2) efficiently heals critical size defects in rats. Translation into possible human clinical trials requires, inter alia, demonstration of efficacy in a large animal, such as the sheep. Scale-up is fraught with numerous biological, anatomical, mechanical and structural variables, which cannot be addressed systematically because of cost and other practical issues. For this reason, we developed a translational model enabling us to isolate the biological question of whether sheep muscle, transduced with adenovirus expressing BMP-2, could heal critical size defects in vivo. Initial experiments in athymic rats noted strong healing in only about one-third of animals because of unexpected immune responses to sheep antigens. For this reason, subsequent experiments were performed with Fischer rats under transient immunosuppression. Such experiments confirmed remarkably rapid and reliable healing of the defects in all rats, with bridging by 2 weeks and remodelling as early as 3-4 weeks, despite BMP-2 production only in nanogram quantities and persisting for only 1-3 weeks. By 8 weeks the healed defects contained well-organised new bone with advanced neo-cortication and abundant marrow. Bone mineral content and mechanical strength were close to normal values. These data demonstrate the utility of this model when adapting this technology for bone healing in sheep, as a prelude to human clinical trials

Use of genetically modified muscle and fat grafts to repair defects in bone and cartilage

We report a novel technology for the rapid healing of large osseous and chondral defects, based upon the genetic modification of autologous skeletal muscle and fat grafts. These tissues were selected because they not only possess mesenchymal progenitor cells and scaffolding properties, but also can be biopsied, genetically modified and returned to the patient in a single operative session. First generation adenovirus vector carrying cDNA encoding human bone morphogenetic protein-2 (Ad.BMP-2) was used for gene transfer to biopsies of muscle and fat. To assess bone healing, the genetically modified ("gene activated") tissues were implanted into 5mm-long critical size, mid-diaphyseal, stabilized defects in the femora of Fischer rats. Unlike control defects, those receiving gene-activated muscle underwent rapid healing, with evidence of radiologic bridging as early as 10 days after implantation and restoration of full mechanical strength by 8 weeks. Histologic analysis suggests that the grafts rapidly differentiated into cartilage, followed by efficient endochondral ossification. Fluorescence in situ hybridization detection of Y-chromosomes following the transfer of male donor muscle into female rats demonstrated that at least some of the osteoblasts of the healed bone were derived from donor muscle. Gene activated fat also healed critical sized defects, but less quickly than muscle and with more variability. Anti-adenovirus antibodies were not detected. Pilot studies in a rabbit osteochondral defect model demonstrated the promise of this technology for healing cartilage defects. Further development of these methods should provide ways to heal bone and cartilage more expeditiously, and at lower cost, than is presently possible

A study of CP violation in the decays B±→[K+K-π+π-]Dh± (h= K, π) and B±→[π+π-π+π-]Dh±

The first study of CP violation in the decay mode B±→[K+K-π+π-]Dh± , with h= K, π , is presented, exploiting a data sample of proton–proton collisions collected by the LHCb experiment that corresponds to an integrated luminosity of 9 \,fb - 1 . The analysis is performed in bins of phase space, which are optimised for sensitivity to local CP asymmetries. CP -violating observables that are sensitive to the angle γ of the Unitarity Triangle are determined. The analysis requires external information on charm-decay parameters, which are currently taken from an amplitude analysis of LHCb data, but can be updated in the future when direct measurements become available. Measurements are also performed of phase-space integrated observables for B±→[K+K-π+π-]Dh± and B±→[π+π-π+π-]Dh± decays

Study of charmonium decays to KS0KπK^0_S K \pi in the B→(KS0Kπ)KB \to (K^0_S K \pi) K channels

A study of the $B^+\to K^0_SK^+K^-\pi^+$ and $B^+\to K^0_SK^+K^+\pi^-$ decays is performed using proton-proton collisions at center-of-mass energies of 7, 8 and 13 TeV at the LHCb experiment. The $K^0_SK \pi$ invariant mass spectra from both decay modes reveal a rich content of charmonium resonances. New precise measurements of the $\eta_c$ and $\eta_c(2S)$ resonance parameters are performed and branching fraction measurements are obtained for $B^+$ decays to $\eta_c$, $J/\psi$, $\eta_c(2S)$ and $\chi_{c1}$ resonances. In particular, the first observation and branching fraction measurement of $B^+ \to \chi_{c0} K^0 \pi^+$ is reported as well as first measurements of the $B^+\to K^0K^+K^-\pi^+$ and $B^+\to K^0K^+K^+\pi^-$ branching fractions. Dalitz plot analyses of $\eta_c \to K^0_SK\pi$ and $\eta_c(2S) \to K^0_SK\pi$ decays are performed. A new measurement of the amplitude and phase of the $K \pi$ $S$-wave as functions of the $K \pi$ mass is performed, together with measurements of the $K^*_0(1430)$, $K^*_0(1950)$ and $a_0(1700)$ parameters. Finally, the branching fractions of $\chi_{c1}$ decays to $K^*$ resonances are also measured.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-051.html (LHCb public pages

Measurement of ZZ boson production cross-section in pppp collisions at s=5.02\sqrt{s} = 5.02 TeV

The first measurement of the $Z$ boson production cross-section at centre-of-mass energy $\sqrt{s} = 5.02\,$TeV in the forward region is reported, using $pp$ collision data collected by the LHCb experiment in year 2017, corresponding to an integrated luminosity of $100 \pm 2\,\rm{pb^{-1}}$. The production cross-section is measured for final-state muons in the pseudorapidity range $2.0 20\,\rm{GeV/}\it{c}$. The integrated cross-section is determined to be $$\sigma_{Z \rightarrow \mu^{+}\mu^{-}} = 39.6 \pm 0.7\,(\rm{stat}) \pm 0.6\,(\rm{syst}) \pm 0.8\,(\rm{lumi}) \ \rm{pb}$$ for the di-muon invariant mass in the range $60<M_{\mu\mu}<120\,\rm{GeV/}\it{c^{2}}$. This result and the differential cross-section results are in good agreement with theoretical predictions at next-to-next-to-leading order in the strong coupling. Based on a previous LHCb measurement of the $Z$ boson production cross-section in $p$Pb collisions at $\sqrt{s_{NN}}=5.02$ TeV, the nuclear modification factor $R_{p\rm{Pb}}$ is measured for the first time at this energy. The measured values are $1.2^{+0.5}_{-0.3}\,(\rm{stat}) \pm 0.1\,(\rm{syst})$ in the forward region ($1.53<y^*_{\mu}<4.03$) and $3.6^{+1.6}_{-0.9}\,(\rm{stat}) \pm 0.2\,(\rm{syst})$ in the backward region ($-4.97<y^*_{\mu}<-2.47$), where $y^*_{\mu}$ represents the muon rapidity in the centre-of-mass frame.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-010.html (LHCb public pages

Test of lepton flavour universality using B0→D∗−τ+ντB^0 \to D^{*-}\tau^+\nu_{\tau} decays with hadronic τ\tau channels

The branching fraction $\mathcal{B}(B^0 \to D^{*-}\tau^+\nu_{\tau})$ is measured relative to that of the normalisation mode $B^0 \to D^{*-}\pi^+\pi^-\pi^+$ using hadronic $\tau^+ \to \pi^+\pi^-\pi^+(\pi^0)\bar{\nu}_{\tau}$ decays in proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the LHCb experiment, corresponding to an integrated luminosity of 2 fb$^{-1}$. The measured ratio is $\mathcal{B}(B^0 \to D^{*-}\tau^+\nu_{\tau})/\mathcal{B}(B^0 \to D^{*-}\pi^+\pi^-\pi^+)= 1.70 \pm 0.10^{+0.11}_{-0.10}$, where the first uncertainty is statistical and the second is related to systematic effects. Using established branching fractions for the $B^0 \to D^{*-}\pi^+\pi^-\pi^+$ and $B^0 \to D^{*-} \mu^+\nu_\mu$ modes, the lepton universality test, $\mathcal{R}(D^{*-}) \equiv \mathcal{B}(B^0 \to D^{*-}\tau^+\nu_{\tau})/\mathcal{B}(B^0 \to D^{*-} \mu^+\nu_\mu)$ is calculated, $$\mathcal{R}(D^{*-}) = 0.247 \pm 0.015 \pm 0.015 \pm 0.012\, ,$$ where the third uncertainty is due to the uncertainties on the external branching fractions. This result is consistent with the Standard Model prediction and with previous measurements.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-052.html (LHCb public pages

Studies of η\eta and η′\eta' production in pppp and ppPb collisions

The production of $\eta$ and $\eta'$ mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5<y_{\rm c.m.}<3.5$ (forward rapidity) and $-4.0<y_{\rm c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5<p_{\rm T}<10~{\rm GeV}$ and $3<p_{\rm T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as $\eta$ and $\eta'$ meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb public pages

Amplitude analysis of the Λb0→pK−γ decay

The resonant structure of the radiative decay Λb0→pK−γ in the region of proton-kaon invariant-mass up to 2.5 GeV/c2 is studied using proton-proton collision data recorded at centre-of-mass energies of 7, 8, and 13 TeV collected with the LHCb detector, corresponding to a total integrated luminosity of 9 fb−1. Results are given in terms of fit and interference fractions between the different components contributing to this final state. Only Λ resonances decaying to pK− are found to be relevant, where the largest contributions stem from the Λ(1520), Λ(1600), Λ(1800), and Λ(1890) states

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

This 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.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-014.html (LHCb public pages

Measurement of the mass difference and relative production rate of the Ωb−\Omega^-_b and Ξb−\Xi^-_b baryons

The mass difference between the $\Omega^-_b$ and $\Xi^-_b$ baryons is measured using proton-proton collision data collected by the LHCb experiment, corresponding to an integrated luminosity of $9 \, \text{fb}^{-1}$, and is found to be \begin{equation} m(\Omega^-_b)- m(\Xi^-_b) = 248.54 \pm 0.51 \text{(stat)} \pm 0.38 \text{(syst)} \, \text{MeV}/c^2. \end{equation} The mass of the $\Omega^-_b$ baryon is measured to be \begin{equation} m(\Omega^-_b)= 6045.9 \pm 0.5 \text{(stat)} \pm 0.6 \text{(syst)} \, \text{MeV}/c^2. \end{equation} This is the most precise determination of the $\Omega^-_b$ mass to date. In addition, the production rate of $\Omega^-_b$ baryons relative to that of $\Xi^-_b$ baryons is measured for the first time in $pp$ collisions, using an LHCb dataset collected at a center-of-mass energy of $13 \, \text{TeV}$ and corresponding to an integrated luminosity of $6\,\text{fb}^{-1}$. Reconstructing beauty baryons in the kinematic region $2 < \eta < 6$ and $p_T < 20\,\text{GeV}/c$ with their decays to a $J/\psi$ meson and a hyperon, the ratio \begin{equation} \frac{f_{\Omega^-_b}}{f_{\Xi^-_b}}\times\frac{\mathcal{B}(\Omega^-_b \to J/\psi \Omega^-)}{\mathcal{B}(\Xi^-_b \to J/\psi \Xi^-)} = 0.120 \pm 0.008 \text{(stat)} \pm 0.008 \text{(syst)}, \end{equation} is obtained, where $f_{\Omega^-_b}$ and $f_{\Xi^-_b}$ are the fragmentation fractions of $b$ quarks into $\Omega^-_b$ and $\Xi^-_b$ baryons, respectively, and $\mathcal{B}$ represents the branching fractions of their respective decays.Comment: 23 pages, 3 figures. All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-053.html (LHCb public pages