The prognostic value of different glucose abnormalities in patients with acute myocardial infarction treated invasively

BACKGROUND: Diabetes (DM) deteriorates the prognosis in patients with coronary heart disease. However, the prognostic value of different glucose abnormalities (GA) other than DM in subjects with acute myocardial infarction (AMI) treated invasively remains unclear. AIMS: To assess the incidence and impact of GA on clinical outcomes in AMI patients treated with percutaneous coronary intervention (PCI). METHODS: A single-center, prospective registry encompassed 2733 consecutive AMI subjects treated with PCI. In all in-hospital survivors (n = 2527, 92.5%) without the history of DM diagnosed before or during index hospitalization standard oral glucose tolerance test (OGTT) was performed during stable condition before hospital discharge and interpreted according to WHO criteria. The mean follow-up period was 37.5 months. RESULTS: The incidence of GA was as follows: impaired fasting glycaemia - IFG (n = 376, 15%); impaired glucose tolerance - IGT (n = 560, 22%); DM (n = 425, 17%); new onset DM (n = 384, 15%); and normal glucose tolerance – NGT (n = 782, 31%). During the long-term follow-up, death rate events for previously known DM, new onset DM and IGT were significantly more frequent than those for IFG and NGT (12.3; 9.6 and 9.4 vs. 5.6 and 6.4%, respectively, P < 0.05). The strongest and common independent predictors of death in GA patients were glomerular filtration rate < 60 ml/min/1,73 m^2 (HR 2.0 and 2.8) and left ventricle ejection fraction < 35% (HR 2.5 and 1.8, all P < 0.05) respectively. CONCLUSIONS: Glucose abnormalities are very common in AMI patients. DM, new onset DM and IGT increase remote mortality. Impaired glucose tolerance bears similar long-term prognosis as diabetes

Guideline-adherent antithrombotic treatment improves outcomes in patients with atrial fibrillation::Insights from the community-based Darlington atrial fibrillation registry

Objective: To assess the influence of guideline-adherent versus non-adherentantithrombotic treatment (ATT) on stroke and mortality rates in atrial fibrillation (AF) primary care population.Patients and Methods: We used Darlington Registry cohort which included 105,000 patients from March 31, 2012, through March 31, 2013. Guideline-adherence in ATT was assessed against 2014 National Institute for Health and Care Excellence (NICE) guidelines, which recommend oral anticoagulation (OAC) for stroke prevention as a default management unless a truly “low-risk” of stroke (CHA2DS2-VASc=0 in men and 1 in women) is evident.Results: Overall, 2259 (2.15%) AF patients were identified, of which 36.1% were undertreated, 50.8% guideline-adherent and 13.1% over-treated. OAC was declined by 5.0% and contraindicated at 8.3%. Overall, 67 (3.0%) incident strokes occurred, of which 66 (98.5%) in high-risk patients (CHA2DS2-VASc ≥2). For the high-risk cohort, one-year stroke rates were 4.5% (95% CI 3.2-6.3) for under-treatment, 1.9% (95% CI 1.2-2.9) for guideline-adherence, and 7.2% (95% CI 4.4-11.6) for over-treatment; corresponding mortality rates were 16.1%(95% CI 13.6-19.0), 8.0% (95% CI 6.5-9.8), and 8.2% (95% CI 5.2-12.7), respectively. On multivariable analysis, both under- and over-treatment of high-risk patients were associated with significant increase in stroke rates (OR 2.32, 95% CI 1.30-3.14, P=.005 and OR 2.28, 95% CI 1.12-4.63, P=.02, respectively). Under-treatment was also associated with a significant increase in all-cause mortality (OR 1.59, 95% CI 1.14-2.21, P=.006). Conclusion: Only half of eligible AF patients are prescribed OAC in accordance with guideline recommendations. Guideline-adherent ATT significantly reduces the risk of stroke and improves survival.<br/

Analyses of 1236 genotyped primary ciliary dyskinesia individuals identify regional clusters of distinct DNA variants and significant genotype–phenotype correlations

Background Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes. Methods Genetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV1)) were collected from 19 countries using the European Reference Network’s ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV1. Results The study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47–100%) and laterality defects (mean 42%, range 28–69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV1 z-score (−1.66). Median FEV1 z-scores were significantly lower in CCNO (−3.26), CCDC39 (−2.49) and CCDC40 (−2.96) variant groups, while the FEV1 z-score reductions were significantly milder in DNAH11 (−0.83) and ODAD1 (−0.85) variant groups compared to the whole PCD cohort. Conclusion This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function.</p

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.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-2022-013.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in 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-2022-039.html (LHCb public pages

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Development of the Active Radiation Monitoring System of the LHCb Experiment at CERN

The main goal of this work was to improve the LHCb Active Radiation Monitoring System (LbARMS) of the LHCb Experiment taking place at the European Organization for Nuclear Research (CERN). A new predictive algorithm was devised based on the Outlier-Robust Kalman Filter and Rauch-Tung-Striebel formula. The algorithm operates in quasi-real time in a Supervisory Control And Data Acquisition (SCADA) system. In addition, a new calibration model was suggested for RADFETs (RADiation-sensitive Field Effect Transistors) covering saturating range. A new Graphical User Interface (GUI) was created, which displays and monitors the results produced by the correction algorithm. It also assists the user in replacing the sensors if necessary. Finally, LbECSData and LbARMS web APIs were developed in order to read and present data coming from the Experiment Control System (ECS)

New simulation software and machine learning technologies in the LHCb experiment to evaluate physics performance of Run 3

The main goal of the work presented in this thesis was to explore new software and machine learning-based technologies to improve the performance of the LHCb data processing applications and, in particular, the simulation framework of LHCb, Gauss. Gaussino is the new core simulation framework that was created by extracting all the experiment-independent functionalities of Gauss. In this work, the Gaussino framework was moved from the advanced prototype stage to the production-ready framework, which can act as an ideal test bed for all the new simulation and detector developments in a standalone mode, as well as a robust core simulation framework for experiments in high-energy physics (HEP). Gauss-on-Gaussino is the new version of the LHCb simulation framework, based on Gaussino. In addition to ensuring the smooth transition to the new simulation framework for Run~3 and beyond, the work included integrating a new interface to fast simulations, adding support for new detector description toolkits (DD4hep and ExternalDetector), as well as new visualization tools and web-based documentation. In addition to the improvements in the software of the simulation framework, new machine learning-based technologies were explored and integrated into the simulation framework. In particular, infrastructure for running Generative AI (GenAI) models for calorimeter fast simulations in Gaussino was integrated. Moreover, the performance of the first, production-ready CaloML+VAE model trained on the LHCb electromagnetic calorimeter data was evaluated. An exploration of the additional use of the machine learning (ML) models in object detection algorithms for cluster energy reconstruction in the LHCb electromagnetic calorimeter was also presented. Finally, validation of the new simulation framework and machine learning-based fast simulation techniques was presented using a few relevant LHCb decay channels in the last chapter of this thesis. Validation was done with respect to samples produced with Gauss framework when using the well-tested Geant4 toolkit