Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2

BACKGROUND: The 12-week, phase III Pulmonary Arterial hyperTENsion sGC-stimulator Trial (PATENT)-1 study investigated riociguat in patients with pulmonary arterial hypertension (PAH). Here, we present a prospectively planned analysis of the safety and efficacy of riociguat in the subgroup of patients with PAH associated with connective tissue disease (PAH-CTD). METHODS: Patients with PAH-CTD were further classified post hoc as having PAH associated with systemic sclerosis or PAH-other defined CTD. In PATENT-1, patients received riociguat (maximum 2.5 or 1.5 mg three times daily) or placebo. Efficacy endpoints included change from baseline in 6-minute walking distance (6MWD; primary endpoint), haemodynamics and WHO functional class (WHO FC). In the long-term extension PATENT-2, patients received riociguat (maximum 2.5 mg three times daily); the primary endpoint was safety and tolerability. RESULTS: In patients with PAH-CTD, riociguat increased mean 6MWD, WHO FC, pulmonary vascular resistance and cardiac index. Improvements in 6MWD and WHO FC persisted at 2 years. Two-year survival of patients with PAH-CTD was the same as for idiopathic PAH (93%). Riociguat had a similar safety profile in patients with PAH-CTD to that of the overall population. CONCLUSIONS: Riociguat was well tolerated and associated with positive trends in 6MWD and other endpoints that were sustained at 2 years in patients with PAH-CTD. TRIAL REGISTRATION NUMBERS: PATENT-1 (NCT00810693), PATENT-2 (NCT00863681)

Synthesis of phosphonate-functionalized polystyrene and poly(methyl methacrylate) particles and their kinetic behavior in miniemulsion polymerization

Phosphonate-functionalized polymer nanoparticles were synthesized by free-radical copolymerization of vinylphosphonic acid (VPA) with styrene or methyl methacrylate (MMA) using the miniemulsion technique. The influence of different parameters such as monomer and surfactant type, amount of vinylphosphonic acid on the average particle size, and size distribution was studied using dynamic light scattering and transmission electron microscopy. Depending on the amount and type of the surfactant used (ionic or non-ionic), phosphonate-functionalized particles in a size range from 102 to 312 nm can be obtained. The density of the phosphonate groups on the particle surface was higher in the case of using MMA as a basis monomer than polystyrene. The kinetic behavior of VPA copolymerization with styrene or MMA using a hydrophobic initiator was investigated by reaction calorimetry. Different kinetic curves were observed for miniemulsion (co)polymerization of styrene- and MMA-based nanoparticles indicating different nucleation mechanisms

Forward modeling of collective Thomson scattering for Wendelstein 7-X plasmas: Electrostatic approximation

In this paper, we present a method for numerical computation of collective Thomson scattering (CTS). We developed a forward model, eCTS, in the electrostatic approximation and benchmarked it against a full electromagnetic model. Differences between the electrostatic and the electromagnetic models are discussed. The sensitivity of the results to the ion temperature and the plasma composition is demonstrated. We integrated the model into the Bayesian data analysis framework Minerva and used it for the analysis of noisy synthetic data sets produced by a full electromagnetic model. It is shown that eCTS can be used for the inference of the bulk ion temperature. The model has been used to infer the bulk ion temperature from the first CTS measurements on Wendelstein 7-X

Towards a new image processing system at Wendelstein 7-X: From spatial calibration to characterization of thermal events

Wendelstein 7-X (W7-X) is the most advanced fusion experiment in the stellarator line and is aimed at proving that the stellarator concept is suitable for a fusion reactor. One of the most important issues for fusion reactors is the monitoring of plasma facing components when exposed to very high heat loads, through the use of visible and infrared (IR) cameras. In this paper, a new image processing system for the analysis of the strike lines on the inboard limiters from the first W7-X experimental campaign is presented. This system builds a model of the IR cameras through the use of spatial calibration techniques, helping to characterize the strike lines by using the information given by real spatial coordinates of each pixel. The characterization of the strike lines is made in terms of position, size, and shape, after projecting the camera image in a 2D grid which tries to preserve the curvilinear surface distances between points. The description of the strike-line shape is made by means of the Fourier Descriptors

The socio-economic module of the Berlin Aging Study II (SOEP-BASE): Description, structure, and questionnaire

Böckenhoff A, Saßenroth D, Kroh M, Siedler T, Eibich P, Wagner GG. The Socio-Economic Module of the Berlin Aging Study II (SOEP-BASE) : Description, Structure, and Questionnaire. SOEPpapers on Multidisciplinary Panel Data Research. Vol 568. Berlin: DIW Berlin; 2013.The Berlin Aging Study II (BASE-II) is a multidisciplinary study that allows for the investigation of how a multitude of health status factors as well as many other social and economic outcomes interplay. The sample consists of 1,600 participants aged 60 to 80, and 600 participants aged 20 to 35. The socio-economic part of BASE-II, the so called SOEP-BASE, is conducted by the SOEP Group at the DIW Berlin. The surveyed socio-economic variables are fully comparable with the variables of the long running German Socio-Economic Panel Study (SOEP), which increases the analytical power of BASE-II. The socio-economic data collected on the individual and on the household level are enriched with geo-referenced context data (neighbourhood data) in order to disentangle the interplay between individual, societal and regional determinants on individuals' health status and other outcome variables. Furthermore, as the BASE-II study is based on a convenience sample, the SOEP Group at the DIW provides weights for the BASE-II dataset that correct for selectivity bias

Some corrections of the significance level in meta-analysis

In many applications we obtain test statistics by combining estimates from different experiments or studies. The usual combined estimator of the overall effect in independent studies leads to systematic overestimates of the significance level, see Li et al. (1994). This results in a great number of unjustified significant evidences. By examination of the convexity of composed functions involved and application of higher and inverse moments of the chi-square distribution we propose corrections for the estimated standard deviation of the overall effect estimator. Analytical results and simulations show that we improve the estimated significance level in such models. (orig.)Available from TIB Hannover: RR 8460(1998,23) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman