Type 2 diabetes and reduced exercise tolerance: A review of the literature through an integrated physiology approach

The association between type 2 diabetes mellitus (T2DM) and heart failure (HF) is well established. Early in the course of the diabetic disease, some degree of impaired exercise capacity (a powerful marker of health status with prognostic value) can be frequently highlighted in otherwise asymptomatic T2DM subjects. However, the literature is quite heterogeneous, and the underlying pathophysiologic mechanisms are far from clear. Imaging-cardiopulmonary exercise testing (CPET) is a non-invasive, provocative test providing a multi-variable assessment of pulmonary, cardiovascular, muscular, and cellular oxidative systems during exercise, capable of offering unique integrated pathophysiological information. With this review we aimed at defying the cardiorespiratory alterations revealed through imaging-CPET that appear specific of T2DM subjects without overt cardiovascular or pulmonary disease. In synthesis, there is compelling evidence indicating a reduction of peak workload, peak oxygen assumption, oxygen pulse, as well as ventilatory efficiency. On the contrary, evidence remains inconclusive about reduced peripheral oxygen extraction, impaired heart rate adjustment, and lower anaerobic threshold, compared to non-diabetic subjects. Based on the multiparametric evaluation provided by imaging-CPET, a dissection and a hierarchy of the underlying mechanisms can be obtained. Here we propose four possible integrated pathophysiological mechanisms, namely myocardiogenic, myogenic, vasculogenic and neurogenic. While each hypothesis alone can potentially explain the majority of the CPET alterations observed, seemingly different combinations exist in any given subject. Finally, a discussion on the effects -and on the physiological mechanisms-of physical activity and exercise training on oxygen uptake in T2DM subjects is also offered. The understanding of the early alterations in the cardiopulmonary response that are specific of T2DM would allow the early identification of those at a higher risk of developing HF and possibly help to understand the pathophysiological link between T2DM and HF

A Calculus for Orchestration of Web Services

We introduce COWS (Calculus for Orchestration of Web Services), a new foundational language for SOC whose design has been influenced by WS-BPEL, the de facto standard language for orchestration of web services. COWS combines in an original way a number of ingredients borrowed from well-known process calculi, e.g. asynchronous communication, polyadic synchronization, pattern matching, protection, delimited receiving and killing activities, while resulting different from any of them. Several examples illustrates COWS peculiarities and show its expressiveness both for modelling imperative and orchestration constructs, e.g. web services, flow graphs, fault and compensation handlers, and for encoding other process and orchestration languages

Is there life inside black holes?

Bound inside rotating or charged black holes, there are stable periodic planetary orbits, which neither come out nor terminate at the central singularity. Stable periodic orbits inside black holes exist even for photons. These bound orbits may be defined as orbits of the third kind, following the Chandrasekhar classification of particle orbits in the black hole gravitational field. The existence domain for the third kind orbits is rather spacious, and thus there is place for life inside supermassive black holes in the galactic nuclei. Interiors of the supermassive black holes may be inhabited by civilizations, being invisible from the outside. In principle, one can get information from the interiors of black holes by observing their white hole counterparts.Comment: 11 pages, 5 figures; references adde

Debugging of Web Applications with Web-TLR

Web-TLR is a Web verification engine that is based on the well-established Rewriting Logic--Maude/LTLR tandem for Web system specification and model-checking. In Web-TLR, Web applications are expressed as rewrite theories that can be formally verified by using the Maude built-in LTLR model-checker. Whenever a property is refuted, a counterexample trace is delivered that reveals an undesired, erroneous navigation sequence. Unfortunately, the analysis (or even the simple inspection) of such counterexamples may be unfeasible because of the size and complexity of the traces under examination. In this paper, we endow Web-TLR with a new Web debugging facility that supports the efficient manipulation of counterexample traces. This facility is based on a backward trace-slicing technique for rewriting logic theories that allows the pieces of information that we are interested to be traced back through inverse rewrite sequences. The slicing process drastically simplifies the computation trace by dropping useless data that do not influence the final result. By using this facility, the Web engineer can focus on the relevant fragments of the failing application, which greatly reduces the manual debugging effort and also decreases the number of iterative verifications.Comment: In Proceedings WWV 2011, arXiv:1108.208

Gas Analysis and Monitoring Systems for the RPC Detector of CMS at LHC

The Resistive Plate Chambers (RPC) detector of the CMS experiment at the LHC proton collider (CERN, Switzerland) will employ an online gas analysis and monitoring system of the freon-based gas mixture used. We give an overview of the CMS RPC gas system, describe the project parameters and first results on gas-chromatograph analysis. Finally, we report on preliminary results for a set of monitor RPC.Comment: 9 pages, 8 figures. Presented by Stefano Bianco (Laboratori Nazionali di Frascati dell'INFN) at the IEEE NSS, San Diego (USA), October 200

Incremental value of 3D echocardiography and two-dimensional speckle tracking in the early detection of cardiotoxicity linked to chemotherapy and trastuzumab in patients with HER-2 positive breast cancer

Abstract not availabl

Adding hydroxyurea in combination with ruxolitinib improves clinical responses in hyperproliferative forms of myelofibrosis

Ruxolitinib, an orally bioavailable and selective inhibitor of Janus kinase 1 (JAK1) and JAK2, significantly reduces splenomegaly and disease-related symptoms in patients with myelofibrosis (MF). However, no clear survival benefit has been demonstrated, which may in part reflect suboptimal drug exposure related to lower dosages needed to minimize hematological toxicity, specifically cytopenias. Furthermore, the optimal management of specific conditions such as leukocytosis or thrombocytosis in patients under ruxolitinib therapy is still undefined. In these cases, combining ruxolitinib with a cytoreductive agent like hydroxyurea might improve hematological response. This observational multi-center study enrolled 20 adult patients with intermediate- or high-risk primary MF, post- polycythemia vera MF, or postessential thrombocythemia MF with hyperproliferative manifestations of the disease and WBC and/or platelet counts not controlled by ruxolitinib therapy. The patients received treatment with a combination of ruxolitinib and hydroxyurea. A clinical response of any type was obtained in 8 patients (40%) during ruxolitinib monotherapy and in 17 patients (85%) during ruxolitinib-hydroxyurea combination (P = 0.003). After a median duration of 12.4 months of combination therapy, 16/20 patients had a hematological response; 14/17 patients who had started combination therapy to control WBC count and 2/3 who started in order to reduce platelets count. The number of patients requiring ruxolitinib dosage reduction or discontinuations was lower during combination therapy and, at the end of follow-up the median ruxolitinib dose was increased in 50% of patients. In conclusion, the combination of hydroxyurea with ruxolitinib yielded a high clinical response rate and increased ruxolitinib exposure in patients with hyperproliferative forms of MF