Skeletal muscle alterations in tachycardia-induced heart failure are linked to deficient natriuretic peptide signalling and are attenuated by RAS-/NEP-inhibition

Background Heart failure induced cachexia is highly prevalent. Insights into disease progression are lacking. Methods Early state of left ventricular dysfunction (ELVD) and symptomatic systolic heart failure (HF) were both induced in rabbits by tachypacing. Tissue of limb muscle (LM) was subjected to histologic assessment. For unbiased characterisation of early and late myopathy, a proteomic approach followed by computational pathway-analyses was performed and combined with pathway-focused gene expression analyses. Specimen of thoracic diaphragm (TD) served as control for inactivity-induced skeletal muscle alterations. In a subsequent study, inhibition of the renin-angiotensin-system and neprilysin (RAS-/NEP) was compared to placebo. Results HF was accompanied by loss of protein content (8.7±0.4% vs. 7.0±0.5%, mean±SEM, control vs. HF, p<0.01) and a slow-to-fast fibre type switch, establishing hallmarks of cachexia. In ELVD, the enzymatic set-up of LM and TD shifted to a catabolic state. A disturbed malate-aspartate shuttle went well with increased enzymes of glycolysis, forming the enzymatic basis for enforced anoxic energy regeneration. The histological findings and the pathway analysis of metabolic results drew the picture of suppressed PGC-1α signalling, linked to the natriuretic peptide system. In HF, natriuretic peptide signalling was desensitised, as confirmed by an increase in the ratio of serum BNP to tissue cGMP (57.0±18.6pg/ml/nM/ml vs. 165.8±16.76pg/ml/nM/ml, p<0.05) and a reduced expression of natriuretic peptide receptor-A. In HF, combined RAS-/NEP-inhibition prevented from loss in protein content (8.7±0.3% vs. 6.0±0.6% vs. 8.3±0.9%, Baseline vs. HF-Placebo vs. HF-RAS/NEP, p<0.05 Baseline vs. HF-Placebo, p = 0.7 Baseline vs. HF-RAS/NEP). Conclusions Tachypacing-induced heart failure entails a generalised myopathy, preceding systolic dysfunction. The characterisation of “pre-cachectic” state and its progression is feasible. Early enzymatic alterations of LM depict a catabolic state, rendering LM prone to futile substrate metabolism. A combined RAS-/NEP-inhibition ameliorates cardiac-induced myopathy independent of systolic function, which could be linked to stabilised natriuretic peptide/cGMP/PGC-1α signalling

Coronary arteries anomalies (CAA) as a cause of a sudden cardiac death (SCD) among young athletes - review

Introduction and objective Congenital coronary arteries anomalies (CAA) are one of the most common causes of a sudden cardiac death (SCD) among young athletes. CAA are serious diagnostic and clinical issue because in many patients there are no characteristic clinical symptoms and commonly used tests are not enough to reveal many types of anatomical abnormalities. Authors of this review would like to present current state of knowledge of CAA and their diagnostics, as well as recommendations for proceeding in patients with diagnosed CAA to prevent SCD. Abbreviated description of the state of knowledge According to statistics CAA are rare congenital heart defects however they are associated with a more frequent occurrence of SCD. The mechanism of this phenomenon has not been fully explained but there are several hypotheses. The most important of which concerns the dimension of the angle of branch of the coronary artery from the sinus of Valsalva. Numerous clinical studies on SCD pay attention to the occurrence of asymptomatic CAA as the main cause of SCD right after hypertrophic cardiomyopathy. Among strategies of proceeding recommended after the diagnosis of CAA, there are pharmacological and surgical treatment, however it hasn't been established which of them is the best for young athletes. Summary One of the most important things to prevent SCD in the course of CAA seems to be creating universal guidelines for early diagnosis and treatment of this congenital defect. Widespread learning first aid and increasing availability of automatic external defibrillators (AED) are also important. SCD of a young athlete is a tragedy not only for the family but also for the whole sporting environment, that is why it is in the public interest to find an answer to the question how we can prevent that cases in the future

Decreased GLUT1/NHE1 RNA expression in whole blood predicts disease severity in patients with COVID‐19

Aims We aimed to assess whether expression of whole‐blood RNA of sodium proton exchanger 1 (NHE1) and glucose transporter 1 (GLUT1) is associated with COVID‐19 infection and outcome in patients presenting to the emergency department with respiratory infections. Furthermore, we investigated NHE1 and GLUT1 expression in the myocardium of deceased COVID‐19 patients. Methods and results Whole‐blood quantitative assessment of NHE1 and GLUT1 RNA was performed using quantitative PCR in patients with respiratory infection upon first contact in the emergency department and subsequently stratified by SARS‐CoV‐2 infection status. Assessment of NHE1 and GLUT1 RNA using PCR was also performed in left ventricular myocardium of deceased COVID‐19 patients. NHE1 expression is up‐regulated in whole blood of patients with COVID‐19 compared with other respiratory infections at first medical contact in the emergency department (control: 0.0021 ± 0.0002, COVID‐19: 0.0031 ± 0.0003, P = 0.01). The ratio of GLUT1 to NHE1 is significantly decreased in the blood of COVID‐19 patients who are subsequently intubated and/or die (severe disease) compared with patients with moderate disease (moderate disease: 0.497 ± 0.083 vs. severe disease: 0.294 ± 0.0336, P = 0.036). This ratio is even further decreased in the myocardium of patients who deceased from COVID‐19 in comparison with the myocardium of non‐infected donors. Conclusions NHE1 and GLUT1 may be critically involved in the disease progression of SARS‐CoV‐2 infection. We show here that SARS‐CoV‐2 infection critically disturbs ion channel expression in the heart. A decreased ratio of GLUT1/NHE1 could potentially serve as a biomarker for disease severity in patients with COVID‐19

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

Physics case for an LHCb Upgrade II - Opportunities in flavour physics, and beyond, in the HL-LHC era

The LHCb Upgrade II will fully exploit the flavour-physics opportunities of the HL-LHC, and study additional physics topics that take advantage of the forward acceptance of the LHCb spectrometer. The LHCb Upgrade I will begin operation in 2020. Consolidation will occur, and modest enhancements of the Upgrade I detector will be installed, in Long Shutdown 3 of the LHC (2025) and these are discussed here. The main Upgrade II detector will be installed in long shutdown 4 of the LHC (2030) and will build on the strengths of the current LHCb experiment and the Upgrade I. It will operate at a luminosity up to 2×1034 cm−2s−1, ten times that of the Upgrade I detector. New detector components will improve the intrinsic performance of the experiment in certain key areas. An Expression Of Interest proposing Upgrade II was submitted in February 2017. The physics case for the Upgrade II is presented here in more depth. CP-violating phases will be measured with precisions unattainable at any other envisaged facility. The experiment will probe b → sl+l−and b → dl+l− transitions in both muon and electron decays in modes not accessible at Upgrade I. Minimal flavour violation will be tested with a precision measurement of the ratio of B(B0 → μ+μ−)/B(Bs → μ+μ−). Probing charm CP violation at the 10−5 level may result in its long sought discovery. Major advances in hadron spectroscopy will be possible, which will be powerful probes of low energy QCD. Upgrade II potentially will have the highest sensitivity of all the LHC experiments on the Higgs to charm-quark couplings. Generically, the new physics mass scale probed, for fixed couplings, will almost double compared with the pre-HL-LHC era; this extended reach for flavour physics is similar to that which would be achieved by the HE-LHC proposal for the energy frontier

LHCb upgrade software and computing : technical design report

This document reports the Research and Development activities that are carried out in the software and computing domains in view of the upgrade of the LHCb experiment. The implementation of a full software trigger implies major changes in the core software framework, in the event data model, and in the reconstruction algorithms. The increase of the data volumes for both real and simulated datasets requires a corresponding scaling of the distributed computing infrastructure. An implementation plan in both domains is presented, together with a risk assessment analysis

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

Measurements of prompt charm production cross-sections in pp collisions at s=5 \sqrt{s}=5 TeV

Production cross-sections of prompt charm mesons are measured using data from $pp$ collisions at the LHC at a centre-of-mass energy of $5\,$TeV. The data sample corresponds to an integrated luminosity of $8.60\pm0.33\,$pb$^{-1}$ collected by the LHCb experiment. The production cross-sections of $D^0$, $D^+$, $D_s^+$, and $D^{*+}$ mesons are measured in bins of charm meson transverse momentum, $p_{\text{T}}$, and rapidity, $y$. They cover the rapidity range $2.0 < y < 4.5$ and transverse momentum ranges $0 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D^0$ and $D^+$ and $1 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D_s^+$ and $D^{*+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of $1 < p_{\text{T}} < 8\, \text{GeV}/c$ are determined to be \begin{equation*} \sigma(pp\rightarrow D^0 X) = 1190 \pm 3 \pm 64\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D^+ X) = 456 \pm 3 \pm 34\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D_s^+ X) = 195 \pm 4 \pm 19\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D^{*+} X)= 467 \pm 6 \pm 40\,\mu\text{b} \end{equation*} where the uncertainties are statistical and systematic, respectively.Production cross-sections of prompt charm mesons are measured using data from pp collisions at the LHC at a centre-of-mass energy of 5 TeV. The data sample corresponds to an integrated luminosity of 8.60 ± 0.33 pb$^{−1}$ collected by the LHCb experiment. The production cross-sections of D$^{0}$, D$^{+}$, D$_{s}^{+}$ , and D$^{∗+}$ mesons are measured in bins of charm meson transverse momentum, p$_{T}$, and rapidity, y. They cover the rapidity range 2.0 < y < 4.5 and transverse momentum ranges 0 < p$_{T}$ < 10 GeV/c for D$^{0}$ and D$^{+}$ and 1 < p$_{T}$ < 10 GeV/c for D$_{s}^{+}$ and D$^{∗+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of 1 < p$_{T}$ < 8 GeV/c are determined to be $\begin{array}{l}\sigma \left( pp\to {D}^0X\right)=1004\pm 3\pm 54\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}^{+}X\right)=402\pm 2\pm 30\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}_s^{+}X\right)=170\pm 4\pm 16\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}^{\ast +}X\right)=421\pm 5\pm 36\mu \mathrm{b},\end{array}$ where the uncertainties are statistical and systematic, respectively.Production cross-sections of prompt charm mesons are measured using data from $pp$ collisions at the LHC at a centre-of-mass energy of $5\,$TeV. The data sample corresponds to an integrated luminosity of $8.60\pm0.33\,$pb$^{-1}$ collected by the LHCb experiment. The production cross-sections of $D^0$, $D^+$, $D_s^+$, and $D^{*+}$ mesons are measured in bins of charm meson transverse momentum, $p_{\text{T}}$, and rapidity, $y$. They cover the rapidity range $2.0<y<4.5$ and transverse momentum ranges $0 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D^0$ and $D^+$ and $1 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D_s^+$ and $D^{*+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of $1 < p_{\text{T}} < 8\, \text{GeV}/c$ are determined to be \sigma(pp\rightarrow D^0 X) = 1004 \pm 3 \pm 54\,\mu\text{b} \sigma(pp\rightarrow D^+ X) = 402 \pm 2 \pm 30\,\mu\text{b} \sigma(pp\rightarrow D_s^+ X) = 170 \pm 4 \pm 16\,\mu\text{b} \sigma(pp\rightarrow D^{*+} X)= 421 \pm 5 \pm 36\,\mu\text{b} where the uncertainties are statistical and systematic, respectively