Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient

Pulmonary arterial hypertension (PAH) is a progressive disease with poor survival outcomes. Bosentan is an oral endothelin-1 receptor antagonist (ERA) that has been shown in a large randomized placebo-controlled trial (BREATHE-1) to be effective at improving exercise tolerance in patients with PAH in functional class III and IV. Further studies have been conducted showing: benefit in smaller subgroups of PAH, eg, congenital heart disease, efficacy in combination with other PAH therapies, eg, sildenafil, improved long-term survival compared with historical controls. More recently, controlled trials of new ERAs have included patients with milder symptoms; those in functional class II. Analysis of the functional class II data is often limited by small numbers. These trials have generally shown a similar treatment effect to bosentan, but there are no controlled trials directly comparing these new ERAs. The EARLY trial exclusively enrolled functional class II patients and assessed hemodynamics at 6 months. Though significant, the reduction in pulmonary vascular resistance is merely a surrogate marker for the intended aim of delaying disease progression. Significant adverse effects associated with bosentan include edema, anemia and transaminase elevation. These may preclude a long duration of treatment. Further studies are required to determine optimum treatment strategy in mild disease

Initiating e-learning by stealth, participation and consultation in a late majority institution

The extent to which opportunities afforded by e-learning are embraced by an institution can depend in large measure on whether it is perceived as enabling and transformative or as a major and disruptive distraction. Most case studies focus on the former. This paper describes how e-learning was introduced into the latter environment. The sensitivity of competing pressures in a research intensive university substantially influenced the manner in which e-learning was promoted. This paper tells that story, from initial stealth to eventual university acknowledgement of the relevance of e-learning specifically to its own context

Risk stratification and response to therapy in patients with pulmonary arterial hypertension and comorbidities: A COMPERA analysis

Background: A diagnosis of idiopathic pulmonary arterial hypertension (IPAH) is frequently made in elderly patients who present with comorbidities, especially hypertension, coronary heart disease, diabetes mellitus, and obesity. It is unknown to what extent the presence of these comorbidities affects the response to PAH therapies and whether risk stratification predicts outcome in patients with comorbidities. Methods: We assessed the database of COMPERA, a European pulmonary hypertension registry, to determine changes after initiation of PAH therapy in WHO functional class (FC), 6-minute walking distance (6MWD), brain natriuretic peptide (BNP) or N-terminal fragment of probrain natriuretic peptide (NT-pro-BNP), and mortality risk assessed by a 4-strata model in patients with IPAH and no comorbidities, 1-2 comorbidities and 3-4 comorbidities. Results: The analysis was based on 1,120 IPAH patients (n = 208 [19%] without comorbidities, n = 641 [57%] with 1-2 comorbidities, and n = 271 [24%] with 3-4 comorbidities). Improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk from baseline to first follow-up were significantly larger in patients with no comorbidities than in patients with comorbidities, while they were not significantly different in patients with 1-2 and 3-4 comorbidities. The 4-strata risk tool predicted survival in patients without comorbidities as well as in patients with 1-2 or 3-4 comorbidities. Conclusions: Our data suggest that patients with IPAH and comorbidities benefit from PAH medication with improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk, albeit to a lesser extent than patients without comorbidities. The 4-strata risk tool predicted outcome in patients with IPAH irrespective of the presence of comorbidities

Two-dimensional projections of an hypercube

We present a method to project a hypercube of arbitrary dimension on the plane, in such a way as to preserve, as well as possible, the distribution of distances between vertices. The method relies on a Montecarlo optimization procedure that minimizes the squared difference between distances in the plane and in the hypercube, appropriately weighted. The plane projections provide a convenient way of visualization for dynamical processes taking place on the hypercube.Comment: 4 pages, 3 figures, Revtex

THE USE OF STANDARDS IN HELIO

HELIO [8] is a project funded under the FP7 program for the discovery and analysis of data for heliophysics. During its development, standards and common frameworks were adopted in three main areas of the project: query services, processing services, and the security infrastructure. After a first, proprietary implementation of the security service, it was suggested moving it to a standard security framework to simplify the enforcement of security on the different sites. As the HELIO front end is built with Spring and the TAVERNA server (HELIO workflow engine) has a security framework compatible with Spring, it has been decided to move the CIS in Spring security [2]. HELIO has two different processing services: one is a generic processing service called HELIO Processing Services (HPS), the other is called Context Service (CTX) and it runs specific IDL procedures. The CTX implements the UWS [4] interface from the IVOA [5], a standard interface for job submission used in the helio and astro-physics community. In its final release, the HPS will expose an UWS compliant interface. Finally, some of the HELIO services perform queries, to simplify the implementation and usage of this services a single query interface (the HELIO Query Interface) has been designed for all these services. The use of these solutions for security, execution, and query allows for easier implementation of the original HELIO architecture and for a simpler deployment of the services

Recurrent episodes of Takotsubo cardiomyopathy in systemic sclerosis

Systemic sclerosis is an autoimmune disease characterized by fibrosis and small vessel vasculopathy, which affects various organ systems, such as the heart. Takotsubo cardiomyopathy is a transient cardiomyopathy in reaction to an emotional or physical trigger. There may be clinical and pathogenetic overlap between Takotsubo cardiomyopathy and primary systemic sclerosis heart disease, and some patients with systemic sclerosis have been diagnosed with recurrent Takotsubo cardiomyopathy. Our large systemic sclerosis clinical cohort was reviewed to identify cases diagnosed with Takotsubo cardiomyopathy. The clinical features, laboratory and imaging results were reviewed and evaluated to perform a comparison between cases. We identified five patients with systemic sclerosis, all female (age 68.6 ± 5.7 years), who were diagnosed with Takotsubo cardiomyopathy. Two of these patients had recurrent episodes: one case with a history of multiple episodes and the other with one recurrence. Typical features included repolarization abnormalities on the electrocardiogram and transient left ventricular dysfunction observed using echocardiography or cardiac magnetic resonance imaging. Our findings build upon previous reports and observations that systemic sclerosis may cause Takotsubo cardiomyopathy. To our knowledge, this is the largest case series of Takotsubo syndrome in patients with systemic sclerosis. This association may provide novel insights into the aetiopathogenesis of Takotsubo cardiomyopathy as part of primary systemic sclerosis heart involvement

Semantics of the Painted Image in Hugo von Hofmannsthal’s Tod des Tizian

Form theories in Hofmannstahl’s aesthetic program aim at a reciprocal empowerment of life and art. Titian’s last painting in Tod des Tizian (1892) has to express a concept of unity and totality of all living things. Most disciples are not able to understand this, as they can’t get free of the model of existence of the aesthete, who rejects life, perceiving it as abandoned to chaos and disorder, but is incapable of replacing it with any other form because he exalts art as an object of mere idolatry, as a pure and simple instrument of defence from the pitfalls of life

Calibrating and testing tissue equivalent proportional counters with 37Ar

A method for testing and calibrating tissue equivalent proportional counters with37Ar is described.37Ar is produced by exposure of argon in its normal isotope composition to thermal neutrons. It is shown that - up to volume ratios of 0.01 of argon to the tissue equivalent gas - there is no appreciable effect of the argon admixture on the function of the proportional counter. Conventional calibration methods with characteristic x-rays or with -particles require modifications of the detectors, and they test only small sub-volumes in the counters. In contrast, argon permits calibrations and tests of the resolution that are representative for the entire counter volume and that do not require changes in detector construction. The method is equally applicable to multi-element proportional counters; it is here exemplified by its application to a long cylindrical counter of simplified design that is part of such a multi-element configuration

Dynamic prediction of pulmonary hypertension in systemic sclerosis using landmark analysis

OBJECTIVE: Pulmonary hypertension (PH) is a serious complication of systemic sclerosis (SSc). We explore prediction of short-term risk for PH using serial pulmonary function tests (PFTs) and other disease features. METHODS: Subjects with SSc, disease onset≥10 years prior to data retrieval, available autoantibody specificity and PFTs were included. Mixed effects modelling was used to describe change in PFTs over time. Landmarking was utilized to include serial assessments and stratified Cox proportional hazards regression analysis with landmarks as strata was used to develop the PH prediction models. RESULTS: We analysed 1247 SSc patients, 16.3% male, 35.8% with dcSSc. Anticentromere, anti-topoisomerase and anti-RNA polymerase antibodies were observed in 29.8%, 22.0% and 11.4% respectively and PH developed in 13.6%. Over time diffusing capacity for carbon monoxide (DLco) and carbon monoxide transfer coefficient (Kco) declined in all SSc patients (up to 1.5%/year) but demonstrated much greater annual decline (up to 4.5% and 4.8% respectively) in the 5-7 years preceding PH diagnosis. Comparison between multivariable models including either DLco, Kco or FVC/DLco ratio, demonstrated that both absolute values and change over preceding year in those measurements associate strongly with risk of PH (HR 0.93 and 0.76 for Kco and its change; HR 0.90 and 0.96 for DLco and its change; and HR 1.08 and 2.01 for FVC/DLco ratio and its change; p<0.001 for all). The Kco based model had the greatest discriminating ability (Harrell's C 0.903). CONCLUSION: Our findings strongly support the importance of PFT trends over time in identifying patients at risk of PH. This article is protected by copyright. All rights reserved

Balloon Pulmonary Angioplasty: State of the Art

Balloon pulmonary angioplasty (BPA) is a novel technique for the treatment of chronic thromboembolic pulmonary hypertension. While cardiologists need no introduction to the concept of balloon angioplasty, BPA has its own particular challenges. This article aims to provide the reader with an overview of BPA, starting with an introduction to chronic thromboembolic disease (CTED), the standard management of chronic thromboembolic pulmonary hypertension (CTEPH), technical challenges faced when performing BPA and the evidence base supporting its use. The second part of the article will focus on the future of BPA, in particular the areas where research is required to establish an evidence base to justify the role of BPA in CTEPH and CTED treatment