Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients

The dynamics of human behaviour in poker

In this paper we investigate the evolutionary dynamics of strategic behaviour in the game of poker by means of data gathered from a large number of real-world poker games. We perform this study from an evolutionary game theoretic perspective using the Replicator Dynamics model. We investigate the dynamic properties by studying how players switch between different strategies under different circumstances, what the basins of attraction of the equilibria look like, and what the stability properties of the attractors are. We illustrate the dynamics using a simplex analysis. Our experimental results confirm existing domain knowledge of the game, namely that certain strategies are clearly inferior while others can be successful given certain game conditions

The dynamics of human behaviour in poker

In this paper we investigate the evolutionary dynamics of strategic behaviour in the game of poker by means of data gathered from a large number of real-world poker games. We perform this study from an evolutionary game theoretic perspective using the Replicator Dynamics model. We investigate the dynamic properties by studying how players switch between different strategies under different circumstances, what the basins of attraction of the equilibria look like, and what the stability properties of the attractors are. We illustrate the dynamics using a simplex analysis. Our experimental results confirm existing domain knowledge of the game, namely that certain strategies are clearly inferior while others can be successful given certain game conditions

The dynamics of human behaviour in poker

In this paper we investigate the evolutionary dynamics of strategic behaviour in the game of poker by means of data gathered from a large number of real-world poker games. We perform this study from an evolutionary game theoretic perspective using the Replicator Dynamics model. We investigate the dynamic properties by studying how players switch between different strategies under different circumstances, what the basins of attraction of the equilibria look like, and what the stability properties of the attractors are. We illustrate the dynamics using a simplex analysis. Our experimental results confirm existing domain knowledge of the game, namely that certain strategies are clearly inferior while others can be successful given certain game conditions

Learning with whom to communicate using relational reinforcement learning

Relational reinforcement learning is a promising direction within reinforcement learning research. It upgrades reinforcement learning techniques using relational representations for states, actions, and learned value functions or policies to allow natural representations and abstractions of complex tasks. Multi-agent systems are characterized by their relational structure and present a good example of a complex task. In this article, we show how relational reinforcement learning could be a useful tool for learning in multi-agent systems. We study this approach in more detail on one important aspect of multi-agent systems, i.e., on learning a communication policy for cooperative systems (e.g., resource distribution). Communication between agents in realistic multi-agent systems can be assumed costly, limited, and unreliable. We perform a number of experiments that highlight the conditions in which relational representations can be beneficial when taking the constraints mentioned above into account.keywordsoptimal policyreinforcement learningaction spacemultiagent systemmarkov decision processthese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves

Impact of gamma irradiation on porosity and pore distribution of poly [ethylene-oxide] films: correlation with dielectric and microstructural properties

The structure and morphology of polymers are significantly altered upon exposure to high energy gamma irradiation either through bond breakage i.e. scission or cross-linkage. The present article reports the influence of gamma radiation (1–20 kGy) on the distribution of molecular weight and porosity of the films prepared using irradiated and unirradiated poly-[ethylene oxide] (PEO) powder. The PEO films exhibit pore dimension in the range of 20–500 nm. Selective irradiation is capable of tailoring the pore-size and reducing the multimodal trait to uni-or bimodal upon high energy perturbation. The porosity of PEO films is determined from both 2D-pore surface calculation from SEM images and compared with 3D-BET porosity. Correlation is established among dielectric constant (ε′) and porosity. The magnitude of ε′ increases sharply towards low frequency due to electrode polarization effects. Relaxation time is found to be highest and comparable for 1 and 10 KGy. With increase in irradiation dose, scission is predominant, owing to which smaller polymer fragments are produced which are able to follow fast frequency regime and thereby relax at lesser time.</p