Pathways of Helium Postconditioning induced Cardioprotection

Short cycles of ventilation with anesthetic gases prior to or after prolonged cardiac ischemia, called anesthetic pre- or postconditioning, are known to reduce cardiac damage. The underlying mechanisms include the reperfusion injury salvage (RISK) pathway and involve recruitment of molecular signaling via caveolin (Cav) modulation. Postconditioning with helium (HePoc) mimics cardioprotective effects. In the present study using a rat model, we investigated whether (1) HePoc alters protein or mRNA expression of Cav-1 and -3 and (2) activation of RISK pathway and (3) autophagy associated proteins. Heliox ventilation (70% He, 30% O2) was applied after 25 min of ischemia and tissue from ischemic area at risk (AAR), non-ischemic not area at risk (NAAR), and serum was obtained. Cell fractions of Sham, I/R, I/R+He treated animals were separated and investigated for changes of Cav-1 and Cav-3 protein levels and mRNA expression. Phosphorylation levels were measured to determine RISK pathway activation (Erk1/2, PI3K, PKCε and Akt). Protein levels of autophagy proteins Bcl-1 and sequestosome-1 were also measured. HePoc lead to an increase of Cav-1 mRNA expression compared to I/R only and additionally elevated levels of Cav-1 (P<0.01) and Cav-3 (P<0.05) in the membrane fraction of ischemic myocardium (AAR). RISK pathway kinase Akt was activated more in AAR and NAAR tissue of the HePoc group (both P<0.05). Erk1/2 phosphorylation was higher in AAR (P<0.05) after HePoc. However in NAAR tissue of I/R and HePoc treated animals, pErk1/2 was lower compared to Sham (both P<0.001). PKCε and PI3K showed no significant changes in phosphorylation. Bcl-1 was significantly elevated in the mitochondrial fraction after HePoc in AAR (P<0.05) as well as NAAR (P<0.05), while sequestosome-1 levels showed no difference between groups. We propose that HePoc induces cardioprotection through a network of signalling. Respective mediators may include caveolins, the RISK pathway and autophagic processes

What is new in microcirculation and tissue oxygenation monitoring?

Ensuring and maintaining adequate tissue oxygenation at the microcirculatory level might be considered the holy grail of optimal hemodynamic patient management. However, in clinical practice we usually focus on macro-hemodynamic variables such as blood pressure, heart rate, and sometimes cardiac output. Other macro-hemodynamic variables like pulse pressure or stroke volume variation are additionally used as markers of fluid responsiveness. In recent years, an increasing number of technological devices assessing tissue oxygenation or microcirculatory blood flow have been developed and validated, and some of them have already been incorporated into clinical practice. In this review, we will summarize recent research findings on this topic as published in the last 2 years in the Journal of Clinical Monitoring and Computing (JCMC). While some techniques are already currently used as routine monitoring (e.g. cerebral oxygenation using near-infrared spectroscopy (NIRS)), others still have to find their way into clinical practice. Therefore, further research is needed, particularly regarding outcome measures and cost-effectiveness, since introducing new technology is always expensive and should be balanced by downstream savings. The JCMC is glad to provide a platform for such research

Microcirculatory alterations in critically ill COVID-19 patients analyzed using artificial intelligence

Background: The sublingual microcirculation presumably exhibits disease-specific changes in function and morphology. Algorithm-based quantification of functional microcirculatory hemodynamic variables in handheld vital microscopy (HVM) has recently allowed identification of hemodynamic alterations in the microcirculation associated with COVID-19. In the present study we hypothesized that supervised deep machine learning could be used to identify previously unknown microcirculatory alterations, and combination with algorithmically quantified functional variables increases the model's performance to differentiate critically ill COVID-19 patients from healthy volunteers. Methods: Four international, multi-central cohorts of critically ill COVID-19 patients and healthy volunteers (n = 59/n = 40) were used for neuronal network training and internal validation, alongside quantification of functional microcirculatory hemodynamic variables. Independent verification of the models was performed in a second cohort (n = 25/n = 33). Results: Six thousand ninety-two image sequences in 157 individuals were included. Bootstrapped internal validation yielded AUROC(CI) for detection of COVID-19 status of 0.75 (0.69-0.79), 0.74 (0.69-0.79) and 0.84 (0.80-0.89) for the algorithm-based, deep learning-based and combined models. Individual model performance in external validation was 0.73 (0.71-0.76) and 0.61 (0.58-0.63). Combined neuronal network and algorithm-based identification yielded the highest externally validated AUROC of 0.75 (0.73-0.78) (P < 0.0001 versus internal validation and individual models). Conclusions: We successfully trained a deep learning-based model to differentiate critically ill COVID-19 patients from heathy volunteers in sublingual HVM image sequences. Internally validated, deep learning was superior to the algorithmic approach. However, combining the deep learning method with an algorithm-based approach to quantify the functional state of the microcirculation markedly increased the sensitivity and specificity as compared to either approach alone, and enabled successful external validation of the identification of the presence of microcirculatory alterations associated with COVID-19 status. Keywords: Artificial intelligence; COVID-19; Deep learning; Microcirculation; Neuronal network

Monitoring of the Sublingual Microcirculation During Cardiac Surgery:Current Knowledge and Future Directions

Handheld vital microscopes allow for direct observation of the sublingual microcirculatory perfusion during cardiac surgery. Through the use of handheld vital microscopes, it has been shown that cardiac surgery with cardiopulmonary bypass is associated with reduced and heterogenous microcirculatory perfusion. Microcirculatory impairment can result in inadequate tissue perfusion, leading to perioperative complications and poor outcome. Because microcirculatory impairment can occur despite stable or improved global hemodynamics, there is a yet unmet need for specific monitoring of the microcirculation. Technological advancements may facilitate point-of-care monitoring of microcirculatory perfusion using automated real-time analysis of microcirculatory measurements. Thus, microcirculatory monitoring may create new opportunities for specific microcirculatory treatment as part of hemodynamic management. The implementation of microcirculatory variables into personalized treatment concepts has the potential to improve hemodynamic management during cardiac surgery and thereby improve patient outcomes. Therefore, specific treatment strategies need to be developed to prevent or treat alterations of the microcirculatory perfusion. In the future, the use of handheld vital microscopes for microcirculatory monitoring may help to improve hemodynamic management and outcomes for patients undergoing cardiac surgical procedures

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30