Mechanistic and therapeutic aspects of ischemic myocardial preconditioning

To obtain a better understanding of myocardial ischemia-reperfusion injury and to advance therapeutical application of cardiac adaptation to ischemia, this thesis investigates several mechanistic aspects of ischemic preconditioning with respect to triggers, mediators and possible end-effectors. Adenosine is a well established trigger of ischemic preconditioning which is released during ischemia as a breakdown product of ATP. At least four adenosine receptor subtypes have been identified: A1-, A2a-, A2b- and A3- receptors.221 Both the A1- and the A3- receptor subtypes are believed to trigger myocardial preconditioning.131·153·222 The cardioprotective role of adenosine has been confirmed in all species used for experimental investigation.38 However, based on several studies using selective adenosine receptor antagonists which failed to block ischemic preconditioning, its role in rats is still controversial. 155•156 In these studies the duration of the ischemic stimuli were 3-5 min. Interestingly, Schulz et al. 133 demonstrated in the porcine heart that adenosine plays a significant role after 10-min of coronary artery occlusion. Therefore in chapter 2 we studied the role of adenosine in ischemic preconditioning in rats with respect to the duration of the ischemic stimulu

The long-term course of the Health Assessment Questionnaire in patients with systemic sclerosis

Objective: The Health Assessment Questionnaire-Disability Index is an important outcome measure reflecting functional disability, but knowledge on its course over time in patients with systemic sclerosis is scarce. Therefore, we investigated the long-term course of the Health Assessment Questionnaire-Disability Index and its association with baseline characteristics in systemic sclerosis patients. Methods: Systemic sclerosis patients, fulfilling the European League Against Rheumatism and the American College of Rheumatology 2013 criteria, were included from the Leiden Combined Care in Systemic Sclerosis cohort with annual assessments including the Scleroderma Health Assessment Questionnaire-Disability Index (range = 0-3). The course of the Health Assessment Questionnaire-Disability Index was evaluated over the total follow-up (baseline to last available Health Assessment Questionnaire-Disability Index) and between yearly visits. Based on a minimal clinical important difference of 0.22, courses were categorized into worsening, stable or improvement. The course of the Health Assessment Questionnaire-Disability Index over time was evaluated with linear mixed models. Baseline characteristics were compared between patients with a worsening or improvement of the Health Assessment Questionnaire-Disability Index over the total follow-up period with logistic regression analyses. Results: A total of 517 systemic sclerosis patients were included, with a median follow-up of 7 years (interquartile range = 4-9; 2649 visits) and a baseline Health Assessment Questionnaire-Disability Index of 0.625 (interquartile range = 0.125-1.25). On group level, the Health Assessment Questionnaire-Disability Index is stable with an annual increase of 0.019 (95% confidence interval = 0.011 to 0.027). Looking at subgroups, patients >65 years or who died/were physically unable to come during follow-up had a worse mean Health Assessment Questionnaire-Disability Index. In individual courses from baseline to the last follow-up, the proportions of patients with a clinically meaningful worsening, stable or improved Health Assessment Questionnaire-Disability Index were 35%, 42% and 23%, respectively. Patients with immunosuppressants (odds ratio = 0.5, 95% confidence interval = 0.3 to 0.9) or gastrointestinal involvement (odds ratio = 0.6, 95% confidence interval = 0.4 to 0.9) at baseline showed a reduced chance of worsening of the Health Assessment Questionnaire-Disability Index over the total follow-up period. Conclusion: Over time, the average course of the Health Assessment Questionnaire-Disability Index was stable in systemic sclerosis patients. However, individual courses vary, with worsening occurring in one-third. Worsening occurred less often in individuals using immunosuppressants or with gastrointestinal involvement at baseline.Pathophysiology and treatment of rheumatic disease

A possible relationship between aspects of dentition and feeding in the centrarchid and anabantoid fishes

Certain components of dentition — teeth on the third basibranchial in the Centrarchidae and on the parasphenoid in the anabantoids (sensu lato) — are very rare elsewhere in higher teleostean fishes. Though these basibranchial and parasphenoid teeth in the two fish groups are on opposite sides of the oral cavity, it is hypothesized that they both developed as adaptations for gripping a particular category of food items, namely strong-clawed, hard-shelled, active animals that, once within the oral cavity, would try to crawl out again. A corollary to this hypothesis is that higher teleosts with extensive dentition in the central part of the oral cavity have a grasping jaw bite, which, unlike a piercing, shearing, or crushing jaw bite, does not necessarily kill the prey that is taken into the oral cavity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42630/1/10641_2004_Article_BF00005147.pd

Combination of searches for Higgs boson pairs in pp collisions at \sqrts = 13 TeV with the ATLAS detector

This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb(-1) of proton-proton collision data at a centre-of-mass energy root s = 13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the b (b) over barb (b) over bar, b (b) over barW(+)W(-), b (b) over bar tau(+)tau(-), W+W-W+W-, b (b) over bar gamma gamma and W+W-gamma gamma final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (kappa(lambda)) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to -5.0 &lt; kappa(lambda) &lt; 12.0 (-5.8 &lt; kappa(lambda) &lt; 12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza-Klein Randall-Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model. For complete list of authors see http://dx.doi.org/10.1016/j.physletb.2019.135103</p

Searches for lepton-flavour-violating decays of the Higgs boson in s=13\sqrt{s}=13 TeV pp\mathit{pp} collisions with the ATLAS detector

This Letter presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ , performed with the ATLAS detector at the LHC. The searches are based on a data sample of proton–proton collisions at a centre-of-mass energy √s = 13 TeV, corresponding to an integrated luminosity of 36.1 fb−1. No significant excess is observed above the expected background from Standard Model processes. The observed (median expected) 95% confidence-level upper limits on the leptonflavour-violating branching ratios are 0.47% (0.34+0.13−0.10%) and 0.28% (0.37+0.14−0.10%) for H → eτ and H → μτ , respectively.publishedVersio

Comparison between simulated and observed LHC beam backgrounds in the ATLAS experiment at Ebeam =4 TeV

Results of dedicated Monte Carlo simulations of beam-induced background (BIB) in the ATLAS experiment at the Large Hadron Collider (LHC) are presented and compared with data recorded in 2012. During normal physics operation this background arises mainly from scattering of the 4 TeV protons on residual gas in the beam pipe. Methods of reconstructing the BIB signals in the ATLAS detector, developed and implemented in the simulation chain based on the \textscFluka Monte Carlo simulation package, are described. The interaction rates are determined from the residual gas pressure distribution in the LHC ring in order to set an absolute scale on the predicted rates of BIB so that they can be compared quantitatively with data. Through these comparisons the origins of the BIB leading to different observables in the ATLAS detectors are analysed. The level of agreement between simulation results and BIB measurements by ATLAS in 2012 demonstrates that a good understanding of the origin of BIB has been reached

Evidence for the production of three massive vector bosons with the ATLAS detector

A search for the production of three massive vector bosons in proton-proton collisions is performed using data at $\sqrt{s} = 13$ TeV recorded with the ATLAS detector at the Large Hadron Collider in the years 2015-2017, corresponding to an integrated luminosity of $79.8$ fb$^{-1}$. Events with two same-sign leptons $\ell$ (electrons or muons) and at least two reconstructed jets are selected to search for $WWW \to \ell \nu \ell \nu qq$. Events with three leptons without any same-flavour opposite-sign lepton pairs are used to search for $WWW \to \ell \nu \ell\nu \ell \nu$, while events with three leptons and at least one same-flavour opposite-sign lepton pair and one or more reconstructed jets are used to search for $WWZ \to \ell \nu qq \ell \ell$. Finally, events with four leptons are analysed to search for $WWZ \to \ell \nu \ell \nu \ell \ell$ and $WZZ \to qq \ell \ell \ell \ell$. Evidence for the joint production of three massive vector bosons is observed with a significance of 4.1 standard deviations, where the expectation is 3.1 standard deviations.Comment: 38 pages in total, author list starting page 22, 6 figures, 5 tables, matching published paper in Phys. Lett. B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-2

Prompt and non-prompt J/psi elliptic flow in Pb plus Pb collisions at root S-NN=5.02 TeV with the ATLAS detector

The elliptic flow of prompt and non-prompt J/ \u3c8 was measured in the dimuon decay channel in Pb+Pb collisions at sNN=5.02&nbsp;TeV with an integrated luminosity of 0.42nb-1 with the ATLAS detector at the LHC. The prompt and non-prompt signals are separated using a two-dimensional simultaneous fit of the invariant mass and pseudo-proper decay time of the dimuon system from the J/ \u3c8 decay. The measurement is performed in the kinematic range of dimuon transverse momentum and rapidity 9 &lt; pT&lt; 30 GeV , | y| &lt; 2 , and 0\u201360% collision centrality. The elliptic flow coefficient, v2, is evaluated relative to the event plane and the results are presented as a function of transverse momentum, rapidity and centrality. It is found that prompt and non-prompt J/ \u3c8 mesons have non-zero elliptic flow. Prompt J/ \u3c8v2 decreases as a function of pT, while for non-prompt J/ \u3c8 it is, with limited statistical significance, consistent with a flat behaviour over the studied kinematic region. There is no observed dependence on rapidity or centrality

Search for squarks and gluinos in final states with hadronically decaying tau-leptons, jets, and missing transverse momentum using pp collisions at root s = 13 TeV with the ATLAS detector

A search for supersymmetry in events with large missing transverse momentum, jets, and at least one hadronically decaying τ-lepton is presented. Two exclusive final states with either exactly one or at least two τ-leptons are considered. The analysis is based on proton-proton collisions at √s=13  TeV corresponding to an integrated luminosity of 36.1  fb⁻¹ delivered by the Large Hadron Collider and recorded by the ATLAS detector in 2015 and 2016. No significant excess is observed over the Standard Model expectation. At 95% confidence level, model-independent upper limits on the cross section are set and exclusion limits are provided for two signal scenarios: a simplified model of gluino pair production with τ-rich cascade decays, and a model with gauge-mediated supersymmetry breaking (GMSB). In the simplified model, gluino masses up to 2000 GeV are excluded for low values of the mass of the lightest supersymmetric particle (LSP), while LSP masses up to 1000 GeV are excluded for gluino masses around 1400 GeV. In the GMSB model, values of the supersymmetry-breaking scale are excluded below 110 TeV for all values of tanβ in the range 2 ≤ tanβ ≤ 60, and below 120 TeV for tanβ > 30.M. Aaboud … D. Duvnjak … P. Jackson … J.L. Oliver … A. Petridis … A. Qureshi … A.S. Sharma … M.J. White … et al. [The ATLAS Collaboration

Search for long-lived neutral particles in pp collisions at s√=13 TeV that decay into displaced hadronic jets in the ATLAS calorimeter

This paper describes a search for pairs of neutral, long-lived particles decaying in the ATLAS calorimeter. Long-lived particles occur in many extensions to the Standard Model and may elude searches for new promptly decaying particles. The analysis considers neutral, long-lived scalars with masses between 5 and 400 GeV, produced from decays of heavy bosons with masses between 125 and 1000 GeV, where the long-lived scalars decay into Standard Model fermions. The analysis uses either 10.8 fb−1 or 33.0 fb−1 of data (depending on the trigger) recorded in 2016 at the LHC with the ATLAS detector in proton–proton collisions at a centre-of-mass energy of 13 TeV. No significant excess is observed, and limits are reported on the production cross section times branching ratio as a function of the proper decay length of the long-lived particles