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

Measurement of lepton universality parameters in B+→K+ℓ+ℓ−B^+\to K^+\ell^+\ell^- and B0→K∗0ℓ+ℓ−B^0\to K^{*0}\ell^+\ell^- decays

A simultaneous analysis of the $B^+\to K^+\ell^+\ell^-$ and $B^0\to K^{*0}\ell^+\ell^-$ decays is performed to test muon-electron universality in two ranges of the square of the dilepton invariant mass, $q^2$. The measurement uses a sample of beauty meson decays produced in proton-proton collisions collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of $9$ $\text{fb}^{-1}$. A sequence of multivariate selections and strict particle identification requirements produce a higher signal purity and a better statistical sensitivity per unit luminosity than previous LHCb lepton universality tests using the same decay modes. Residual backgrounds due to misidentified hadronic decays are studied using data and included in the fit model. Each of the four lepton universality measurements reported is either the first in the given $q^2$ interval or supersedes previous LHCb measurements. The results are compatible with the predictions of the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-045.html (LHCb public pages

Charmonium production in pNe collisions at √sNN=68.5 GeV

The measurement of charmonium states produced in proton-neon (pNe) collisions by the LHCb experiment in its fixed-target configuration is presented. The production of J/ψ and ψ(2 S) mesons is studied with a beam of 2.5 TeV protons colliding on gaseous neon targets at rest, corresponding to a nucleon-nucleon centre-of-mass energy sNN=68.5GeV . The data sample corresponds to an integrated luminosity of 21.7 ± 1.4 nb - 1 . The J/ψ and ψ(2 S) hadrons are reconstructed in μ+μ- final states. The J/ψ production cross-section per target nucleon in the centre-of-mass rapidity range y⋆∈ [- 2.29 , 0] is found to be 506±8±46nb/nucleon . The ratio of J/ψ and D cross-sections is evaluated to (1.06 ± 0.02 ± 0.09) % . The ψ(2 S) to J/ψ relative production rate is found to be (1.67 ± 0.27 ± 0.10) % in good agreement with other measurements involving beam and target nuclei of similar sizes

Observation of Cabibbo-suppressed two-body hadronic decays and precision mass measurement of the Ωc0\Omega_{c}^{0} baryon

The first observation of the singly Cabibbo-suppressed $\Omega_{c}^{0}\to\Omega^{-}K^{+}$ and $\Omega_{c}^{0}\to\Xi^{-}\pi^{+}$ decays is reported, using proton-proton collision data at a centre-of-mass energy of $13\,{\rm TeV}$, corresponding to an integrated luminosity of $5.4\,{\rm fb}^{-1}$, collected with the LHCb detector between 2016 and 2018. The branching fraction ratios are measured to be $\frac{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}K^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.0608\pm0.0051({\rm stat})\pm 0.0040({\rm syst})$, $\frac{\mathcal{B}(\Omega_{c}^{0}\to\Xi^{-}\pi^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.1581\pm0.0087({\rm stat})\pm0.0043({\rm syst})\pm0.0016({\rm ext})$. In addition, using the $\Omega_{c}^{0}\to\Omega^{-}\pi^{+}$ decay channel, the $\Omega_{c}^{0}$ baryon mass is measured to be $M(\Omega_{c}^{0})=2695.28\pm0.07({\rm stat})\pm0.27({\rm syst})\pm0.30({\rm ext})\,{\rm MeV}/c^{2}$, improving the precision of the previous world average by a factor of four.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-011.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

First observation of the B+→Ds+Ds−K+B^+ \rightarrow D_s^+ D_s^- K^+ decay

The $B^+ \rightarrow D_s^+ D_s^- K^+$ decay is observed for the first time using proton-proton collision data collected by the LHCb detector at centre-of-mass energies of $7$, $8$ and $13\, \text{TeV}$, corresponding to an integrated luminosity of $9\,\text{fb}^{-1}$. Its branching fraction relative to that of the $B^{+} \rightarrow D^{+} D^{-} K^{+}$ decay is measured to be $$\frac{B\left(B^{+} \rightarrow D_s^{+} D_s^{-} K^{+}\right)}{B\left(B^{+} \rightarrow D^{+} D^{-} K^{+}\right)}=0.525 \pm 0.033 \pm 0.027 \pm 0.034,$$ where the first uncertainty is statistical, the second systematic, and the third is due to the uncertainties on the branching fractions of the $D_s^{\pm} \rightarrow K^{\mp} K^{\pm} \pi^{\pm}$ and $D^{\pm} \rightarrow K^{\mp} \pi^{\pm} \pi^{\pm}$ decays. This measurement fills an experimental gap in the knowledge of the family of Cabibbo$-$favoured $\bar{b} \rightarrow \bar{c} c \bar{s}$ transitions and opens the path for unique studies of spectroscopy in future.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-2022-019.html (LHCb public pages

First observation of a doubly charged tetraquark and its neutral partner

A combined amplitude analysis is performed for the decays $B^0 \rightarrow \overline{D}^0 D^+_s\pi^-$ and $B^+\rightarrow D^- D^+_s\pi^+$, which are related by isospin symmetry. The analysis is based on data collected by the LHCb detector in proton-proton collisions at center-of-mass energies of 7, 8 and 13$\,\rm{TeV}$. The full data sample corresponds to an integrated luminosity of 9$\,\rm{fb^{-1}}$. Two new resonant states with masses of $2.908\pm0.011\pm0.020\,\rm{GeV}$ and widths of $0.136\pm0.023\pm0.011\,\rm{GeV}$ are observed, which decay to $D^+_s\pi^+$ and $D^+_s\pi^-$ respectively. The former state indicates the first observation of a doubly charged open-charm tetraquark state with minimal quark content $[c\bar{s}u\bar{d}]$, and the latter state is a neutral tetraquark composed of $[c\bar{s}\bar{u}d]$ quarks. Both states are found to have spin-parity $0^+$, and their resonant parameters are consistent with each other, which suggests that they belong to an isospin triplet.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-026.html (LHCb public pages

Observation of the Bs0 ⁣→D∗+D∗−B^0_s\!\to D^{*+}D^{*-} decay

The first observation of the $B^0_s\!\to D^{*+}D^{*-}$ decay and the measurement of its branching ratio relative to the $B^0\!\to D^{*+}D^{*-}$ decay are presented. The data sample used corresponds to an integrated luminosity of 9$\,\text{fb}^{-1}$ of proton-proton collisions recorded by the LHCb experiment at centre-of-mass energies of 7, 8 and 13$\,\text{TeV}$ between 2011 and 2018. The decay is observed with a very high significance and the ratio of branching fractions is determined to be \begin{align*} \frac{\mathcal{B}(B^0_s\!\to D^{*+}D^{*-})}{\mathcal{B}(B^0\!\to D^{*+}D^{*-})} = 0.269 \pm 0.032 \pm 0.011 \pm 0.008\, , \end{align*} where the first uncertainty is statistical, the second systematic and the third due to the uncertainty of the fragmentation fraction ratio $f_s/f_d$. The $B^0_s\!\to D^{*+}D^{*-}$ branching fraction is calculated to be \begin{align*} \mathcal{B}(B^0_s\!\to D^{*+}D^{*-}) = (2.15 \pm 0.26 \pm 0.09 \pm 0.06 \pm 0.16)\times 10^{-4} \,, \end{align*} where the fourth uncertainty is due to the $B^0\!\to D^{*+}D^{*-}$ branching fraction.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-023.html (LHCb public pages