Mean Field Theory of Sandpile Avalanches: from the Intermittent to the Continuous Flow Regime

We model the dynamics of avalanches in granular assemblies in partly filled rotating cylinders using a mean-field approach. We show that, upon varying the cylinder angular velocity $\omega$, the system undergoes a hysteresis cycle between an intermittent and a continuous flow regimes. In the intermittent flow regime, and approaching the transition, the avalanche duration exhibits critical slowing down with a temporal power-law divergence. Upon adding a white noise term, and close to the transition, the distribution of avalanche durations is also a power-law. The hysteresis, as well as the statistics of avalanche durations, are in good qualitative agreement with recent experiments in partly filled rotating cylinders.Comment: 4 pages, RevTeX 3.0, postscript figures 1, 3 and 4 appended

Pulmonary hypertension: intensification and personalization of combination Rx (PHoenix): a phase IV randomized trial for the evaluation of dose‐response and clinical efficacy of riociguat and selexipag using implanted technologies

Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital-based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory-approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline-recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory-approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra-patient efficacy of the two treatment approaches

Future perspectives for the treatment of pulmonary arterial hypertension.

Over the past 2 decades, pulmonary arterial hypertension has evolved from a uniformly fatal condition to a chronic, manageable disease in many cases, the result of unparalleled development of new therapies and advances in early diagnosis. However, none of the currently available therapies is curative, so the search for new treatment strategies continues. With a deeper understanding of the genetics and the molecular mechanisms of pulmonary vascular disorders, we are now at the threshold of entering a new therapeutic era. Our working group addressed what can be expected in the near future. The topics span the understanding of genetic variations, novel antiproliferative treatments, the role of stem cells, the right ventricle as a therapeutic target, and strategies and challenges for the translation of novel experimental findings into clinical practice

Discrete Bayesian Network Interpretation of the Cox's Proportional Hazard Model

Cox’s Proportional Hazards (CPH) model is quite likely the most popular modeling technique in survival analysis. While the CPH model is able to represent relationships between a collection of risks and their common effect, Bayesian networks have become an attractive alter-native with far broader applications. Our paper focuses on a Bayesian network interpretation of the CPH model. We provide a method of en-coding knowledge from existing CPH models in the process of knowledge engineering for Bayesian networks. We compare the accuracy of the resulting Bayesian network to the CPH model, Kaplan-Meier estimate, and Bayesian network learned from data using the EM algorithm. Bayesian networks constructed from CPH model lead to much higher accuracy than other approaches, especially when the number of data records is very small

Prostacyclins in pulmonary arterial hypertension: the need for earlier therapy.

Pulmonary arterial hypertension (PAH) is a rare but serious condition, which if untreated, is associated with a 2-3-year median survival time. A number of treatment options are available for PAH, leading to improvements in exercise capacity, symptoms, and hemodynamics. However, the disease remains incurable and most patients will ultimately progress to right heart failure and death. Three classes of drugs are currently available to improve PAH outcomes, although this review will focus solely on a class of potent vasodilators known as prostacyclins. Currently, four prostacyclin analogs are licensed for the treatment of PAH: epoprostenol, treprostinil, and iloprost in the USA and some European countries, and beraprost in Japan and Korea. Prostacyclins have become the treatment of choice in patients with severe PAH, but there is also evidence to suggest that their earlier use may also benefit patients with mild-to-moderate disease. This review discusses the advantages of prostacyclins in terms of their usefulness in patients whose condition has deteriorated following monotherapy with other agents, and their integral role in combination therapy. The latter appears to offer the potential for pulmonary vasculature remodeling and could be regarded as an emerging paradigm to treat and prevent the progression of PAH.Journal ArticleResearch Support, Non-U.S. Gov'tReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe