Circulating biomarkers predicting longitudinal changes in left ventricular structure and function in a general population

Background Serial imaging studies in the general population remain important to evaluate the usefulness of pathophysiologically relevant biomarkers in predicting progression of left ventricular (LV) remodeling and dysfunction. Here, we assessed in a general population whether these circulating biomarkers at baseline predict longitudinal changes in LV structure and function. Methods and Results In 592 participants (mean age, 50.8 years; 51.4% women; 40.5% hypertensive), we derived echocardiographic indexes reflecting LV structure and function at baseline and after 4.7 years. At baseline, we measured alkaline phosphatase, markers of collagen turnover (procollagen type I, C‐terminal telopeptide, matrix metalloproteinase‐1) and high‐sensitivity cardiac troponin T. We regressed longitudinal changes in LV indexes on baseline biomarker levels and reported standardized effect sizes as a fraction of the standard deviation of LV change. After full adjustment, a decline in LV longitudinal strain (−14.2%) and increase in E/e′ ratio over time (+18.9%; P≤0.019) was associated with higher alkaline phosphatase activity at baseline. Furthermore, longitudinal strain decreased with higher levels of collagen I production and degradation at baseline (procollagen type I, −14.2%; C‐terminal telopeptide, −16.4%; P≤0.029). An increase in E/e′ ratio over time was borderline associated with lower matrix metalloproteinase‐1 (+9.8%) and lower matrix metalloproteinase‐1/tissue inhibitor of metalloproteinase‐1 ratio (+11.9%; P≤0.041). Higher high‐sensitivity cardiac troponin T levels at baseline correlated significantly with an increase in relative wall thickness (+23.1%) and LV mass index (+18.3%) during follow‐up (P≤0.035). Conclusions We identified a set of biomarkers predicting adverse changes in LV structure and function over time. Circulating biomarkers reflecting LV stiffness, injury, and collagen composition might improve the identification of subjects at risk for subclinical cardiac maladaptation

Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement

BACKGROUND: Right ventricular (RV) adaptation to acute and chronic pulmonary hypertensive syndromes is a significant determinant of short- and long-term outcomes. Although remarkable progress has been made in the understanding of RV function and failure since the meeting of the NIH Working Group on Cellular and Molecular Mechanisms of Right Heart Failure in 2005, significant gaps remain at many levels in the understanding of cellular and molecular mechanisms of RV responses to pressure and volume overload, in the validation of diagnostic modalities, and in the development of evidence-based therapies. METHODS: A multidisciplinary working group of 20 international experts from the American Thoracic Society Assemblies on Pulmonary Circulation and Critical Care, as well as external content experts, reviewed the literature, identified important knowledge gaps, and provided recommendations. RESULTS: This document reviews the knowledge in the field of RV failure, identifies and prioritizes the most pertinent research gaps, and provides a prioritized pathway for addressing these preclinical and clinical questions. The group identified knowledge gaps and research opportunities in three major topic areas: 1) optimizing the methodology to assess RV function in acute and chronic conditions in preclinical models, human studies, and clinical trials; 2) analyzing advanced RV hemodynamic parameters at rest and in response to exercise; and 3) deciphering the underlying molecular and pathogenic mechanisms of RV function and failure in diverse pulmonary hypertension syndromes. CONCLUSIONS: This statement provides a roadmap to further advance the state of knowledge, with the ultimate goal of developing RV-targeted therapies for patients with RV failure of any etiology

The Potential of Regional Integration Agreements (RIAs) in Enhancing the Credibility of Reform: The Case of the Syrian-European Association Agreement

The effect of 'locking-in' economic reform and enhancing its credibility is generally regarded as one of the most important potential effects of regional integration. Based on a detailed review of the theoretical debate, this paper develops a general framework for assessment to evaluate the ability of RIAs to serve as effective mechanisms for 'commitment' and 'signalling'. In the second part, this assessment framework is applied to the case of the Syrian-European Association Agreement (AA). Syria initialled an AA with the European Union in October 2004, but two and a half years later, this agreement is still pending formal signature. The empirical findings of this study show that despite several shortcomings, the Syrian-European AA, if it were to come into force, should be able to deliver an appropriate mechanism for signalling and commitment and thus to improve the credibility of the Syrian process of reform at home and abroad. A major loophole of the agreement, however, is represented by its lack of incentives to increase the 'rewards for good policy'.Der Effekt der Verankerung von Reformen und die Erhöhung ihrer Glaubwürdigkeit (Lock-in-Effekt) gilt allgemein als einer der wichtigsten Effekte der regionalen Integration. Aufbauend auf einer detaillierten Betrachtung der theoretischen Debatte zum 'Lock-in-Effekt' wird in diesem Papier ein allgemeiner Analyserahmen entworfen, der dazu dient, die Fähigkeit von RIA als Mechanismen der Signalisierung und Selbstbindung zu bewerten. Im anschließenden zweiten Teil wird dieser Analyserahmen auf das Beispiel des Syrisch-Europäischen Assoziierungsabkommens angewendet. Syrien initialisierte im Oktober 2004 ein Assoziierungsabkommen mit der Europäischen Union. Zweieinhalb Jahre später ist dieses Abkommen noch immer nicht formell unterzeichnet. Die Ergebnisse dieser Studie zeigen, dass das Syrisch-Europäische Assoziierungsabkommen - sollte es in Kraft treten - trotz einiger Mängel einen adäquaten Mechanismus der Signalisierung und Selbstbindung liefern und dazu beitragen kann, die Glaubwürdigkeit des syrischen Reformprozesses in - und außerhalb des Landes zu verbessern. Eine wesentliche Schwäche des Abkommensentwurfs liegt allerdings in mangelnden Anreizen für eine 'Belohnung der guten Politik'

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum