Overview: Routes to Open Access

Slides of an overview presentation given at a CESAER workshop on Open Access, February 2nd, 2017, in Brussels Cover major routes to more open access as discussed in the Task Force Open Science of CESAER: (national) open access strategies open access mandates open access incentives open access awareness open access publishing open access infrastructur

Revealing the Resilient Right: Insights into Mechanisms of Right Heart Adaptation

Part I Sex differences and markers for RV maladaptation in PH Sex differences are evident in pulmonary arterial hypertension (PAH) and sex hormones are thought to play a role. In Chapter 2, we observed reduced (DHEA-S) plasma levels in both sexes, but testosterone and androstenedione were reduced in female patients only. Importantly, we also identified a negative association between testosterone and RV adaptation. Furthermore, we show that at end-stage disease the female heart is more severely affected than the male heart, as shown by worse hypertrophy and less capillarization. Our longitudinal data shows that females persevere pressure overload for a longer period which results in a worse end-stage RV phenotype. Natriuretic peptides including Brain Natriuretic peptides (BNP) and Atrial Natriuretic peptide (ANP) are important cardiac biomarkers that regulate cardiovascular homeostasis. In the editorial in Chapter 3 we evaluate new biomarkers to identify RV maladaptation in PH. Furthermore we observed differences in ANP and BNP at gene and protein levels both systemically and locally in the right heart of precapillary PH. In addition, we observed sex differences in release of NT-proBNP in iPSC-CMs that underwent stretch. In Chapter 4 we studied unloading of the right ventricle after pulmonary endarterectomy (PEA) in chronic thromboembolic pulmonary hypertension (CTEPH) patients. Although RV diastolic stiffness normalized after PEA, RV mass did not. The decrease in cellular hypertrophy was relatively larger than the decrease in matrix volume after PEA, which indicates incomplete regression of diffuse RV interstitial fibrosis. This is further supported by the persistent increase in levels of collagen biomarkers post-PEA, suggesting active collagen turnover. Summary part II Phenotyping the right atrium in PH BMP10 is of interest in precapillary PH since the sole source of its production is in the right atrium. We showed increased BMP10 expression and its downstream targets locally in RA tissue of precapillary PH patients. Although systemic levels of BMP10 were higher, BMP10 activity was preserved. We also observed that higher BMP10 activity in precapillary PH is associated with worse RV function, RV maladaptation and RA dysfunction. Interestingly, after pressure unloading of the right heart in CTEPH patients after PEA, we observed a reduction in BMP10 activity. Both RA pressure and volume are associated with survival in PAH-patients and are part of the current risk assessment of patients. In Chapter 6, we aimed to fully characterize alterations in the right atrium in precapillary PH. For the first time, we were able to assess human RA PV loops. We showed that increased RA volume and pressure was most evident at the end of ventricular systole and during atrial contraction in precapillary PH. In Chapter 6 we observed evident signs of adaptation of the right atrium also at histological level. Lastly in Chapter 7, we compared the response of the right ventricle to a similar extent of afterload in patients with PAH and HFpEF. Despite a similar extent of pressure overload, the response of the right heart in HFpEF-PH and PAH was different

C-Reactive Protein and N-Terminal Pro-brain Natriuretic Peptide Levels Correlate With Impaired Cardiorespiratory Fitness in Patients With Heart Failure Across a Wide Range of Ejection Fraction

Background: Impaired cardiorespiratory fitness (CRF) is a hallmark of heart failure (HF). Serum levels of C-reactive protein (CRP), a systemic inflammatory marker, and of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of myocardial strain, independently predict adverse outcomes in HF patients. Whether CRP and/or NT-proBNP also predict the degree of CRF impairment in HF patients across a wide range of ejection fraction is not yet established.Methods: Using retrospective analysis, 200 patients with symptomatic HF who completed one or more treadmill cardiopulmonary exercise tests (CPX) using a symptom-limited ramp protocol and had paired measurements of serum high-sensitivity CRP and NT-proBNP on the same day were evaluated. Univariate and multivariate correlations were evaluated with linear regression after logarithmic transformation of CRP (log10) and NT-proBNP (logN).Results: Mean age of patients was 57 ± 10 years and 55% were male. Median CRP levels were 3.7 [1.5–9.0] mg/L, and NT-proBNP levels were 377 [106–1,464] pg/ml, respectively. Mean peak oxygen consumption (peak VO2) was 16 ± 4 mlO2•kg−1•min−1. CRP levels significantly correlated with peakVO2 in all patients (R = −0.350, p < 0.001) and also separately in the subgroup of patients with reduced left ventricular ejection fraction (LVEF) (HFrEF, N = 109) (R = −0.282, p < 0.001) and in those with preserved EF (HFpEF, N = 57) (R = −0.459, p < 0.001). NT-proBNP levels also significantly correlated with peak VO2 in all patients (R = −0.330, p < 0.001) and separately in patients with HFrEF (R = −0.342, p < 0.001) and HFpEF (R = −0.275, p = 0.032). CRP and NT-proBNP did not correlate with each other (R = 0.05, p = 0.426), but independently predicted peak VO2 (R = 0.421, p < 0.001 and p < 0.001, respectively).Conclusions: Biomarkers of inflammation and myocardial strain independently predict peak VO2 in HF patients. Anti-inflammatory therapies and therapies alleviating myocardial strain may independently improve CRF in HF patients across a large spectrum of LVEF

Measurement of the Higgs boson width and evidence of its off-shell contributions to ZZ production

Since the discovery of the Higgs boson in 2012, detailed studies of its properties have been ongoing. Besides its mass, its width—related to its lifetime—is an important parameter. One way to determine this quantity is to measure its off-shell production, where the Higgs boson mass is far away from its nominal value, and relating it to its on-shell production, where the mass is close to the nominal value. Here we report evidence for such off-shell contributions to the production cross-section of two Z bosons with data from the CMS experiment at the CERN Large Hadron Collider. We constrain the total rate of the off-shell Higgs boson contribution beyond the Z boson pair production threshold, relative to its standard model expectation, to the interval [0.0061, 2.0] at the 95% confidence level. The scenario with no off-shell contribution is excluded at a p-value of 0.0003 (3.6 standard deviations). We measure the width of the Higgs boson as ΓH=3.2−1.7+2.4MeV, in agreement with the standard model expectation of 4.1 MeV. In addition, we set constraints on anomalous Higgs boson couplings to W and Z boson pairs

Search for CP violating top quark couplings in pp collisions at √s = 13 TeV

A preprint version of the article is available at arXiv:2205.07434v2 [hep-ex], https://arxiv.org/abs/2205.07434. It has not been certified by peer review.Results are presented from a search for CP violation in top quark pair production, using proton-proton collisions at a center-of-mass energy of 13 TeV. The data used for this analysis consist of final states with two charged leptons collected by the CMS experiment, and correspond to an integrated luminosity of 35.9 fb−1. The search uses two observables, O1 and O3, which are Lorentz scalars. The observable O1 is constructed from the four-momenta of the charged leptons and the reconstructed top quarks, while O3 consists of the four-momenta of the charged leptons and the b quarks originating from the top quarks. Asymmetries in these observables are sensitive to CP violation, and their measurement is used to determine the chromoelectric dipole moment of the top quark. The results are consistent with the expectation from the standard model. [Figure not available: see fulltext.].SCOAP