A systems approach to social entrepreneurship

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An experimental multiprocessor system for distributed parallel computations.

The availability of low-cost microprocessor chips with efficient instruction sets for specific numerical tasks (signal processors) has been exploited for building a versatile multiprocessor system, consisting of a host minicomputer augmented by a number of joint processors. The host provides a multiuser-multitasking environment and manages system resources and task scheduling. User applications can call upon one or more joint processors for parallel execution of adequately partitioned, computationally intensive numeric operations. Each joint processor has sufficient local memory for storing procedures and data and has access to regions in host memory for shared data. Kernel processes in the host and in the joint processors provide the necessary mechanism for initialization and synchronization of the distributed parallel execution of procedures

Modelling typing disfluencies as finite mixture process

To writing anything on a keyboard at all requires us to know first what to type, then to activate motor programmes for finger movements, and execute these. An interruption in the information flow at any of these stages leads to disfluencies. To capture this combination of fluent typing and typing hesitations, researchers calculate different measures from keystroke-latency data – such as mean inter-keystroke interval and pause frequencies. There are two fundamental problems with this: first, summary statistics ignore important information in the data and frequently result in biased estimates; second, pauses and pause-related measures are defined using threshold values which are, in principle, arbitrary. We implemented a series of Bayesian models that aimed to address both issues while providing reliable estimates for individual typing speed and statistically inferred process disfluencies. We tested these models on a random sample of 250 copy-task recordings. Our results illustrate that we can model copy typing as a mixture process of fluent and disfluent key transitions. We conclude that mixture models (1) map onto the information cascade that generate keystrokes, and (2) provide a principled approach to detect disfluencies in keyboard typing

Monocyte dysfunction in decompensated cirrhosis is mediated by the prostaglandin E2-EP4 pathway

Background & Aims: Infection is a major problem in advanced liver disease secondary to monocyte dysfunction. Elevated prostaglandin (PG)E2 is a mediator of monocyte dysfunction in cirrhosis; thus, we examined PGE2 signalling in outpatients with ascites and in patients hospitalised with acute decompensation to identify potential therapeutic targets aimed at improving monocyte dysfunction. Methods: Using samples from 11 outpatients with ascites and 28 patients hospitalised with decompensated cirrhosis, we assayed plasma levels of PGE2 and lipopolysaccharide (LPS); performed quantitative real-time PCR on monocytes; and examined peripheral blood monocyte function. We performed western blotting and immunohistochemistry for PG biosynthetic machinery expression in liver tissue. Finally, we investigated the effect of PGE2 antagonists in whole blood using polychromatic flow cytometry and cytokine production. Results: We show that hepatic production of PGE2 via the cyclo-oxygenase 1–microsomal PGE synthase 1 pathway, and circulating monocytes contributes to increased plasma PGE2 in decompensated cirrhosis. Transjugular intrahepatic sampling did not reveal whether hepatic or monocytic production was larger. Blood monocyte numbers increased, whereas individual monocyte function decreased as patients progressed from outpatients with ascites to patients hospitalised with acute decompensation, as assessed by Human Leukocyte Antigen (HLA)–DR isotype expression and tumour necrosis factor alpha and IL6 production. PGE2 mediated this dysfunction via its EP4 receptor. Conclusions: PGE2 mediates monocyte dysfunction in decompensated cirrhosis via its EP4 receptor and dysfunction was worse in hospitalised patients compared with outpatients with ascites. Our study identifies a potential drug target and therapeutic opportunity in these outpatients with ascites to reverse this process to prevent infection and hospital admission. Lay summary: Patients with decompensated cirrhosis (jaundice, fluid build-up, confusion, and vomiting blood) have high infection rates that lead to high mortality rates. A white blood cell subset, monocytes, function poorly in these patients, which is a key factor underlying their sensitivity to infection. We show that monocyte dysfunction in decompensated cirrhosis is mediated by a lipid hormone in the blood, prostaglandin E2, which is present at elevated levels, via its EP4 pathway. This dysfunction worsens when patients are hospitalised with complications of cirrhosis compared with those in the outpatients setting, which supports the EP4 pathway as a potential therapeutic target for patients to prevent infection and hospitalisation

Aerobic interval training and continuous training equally improve aerobic exercise capacity in patients with coronary artery disease:The SAINTEX-CAD study

AbstractBackgroundExercise-based cardiac rehabilitation increases peak oxygen uptake (peak VO2), which is an important predictor of mortality in cardiac patients. However, it remains unclear which exercise characteristics are most effective for improving peak VO2 in coronary artery disease (CAD) patients. Proof of concept papers comparing Aerobic Interval Training (AIT) and Moderate Continuous Training (MCT) were conducted in small sample sizes and findings were inconsistent and heterogeneous. Therefore, we aimed to compare the effects of AIT and Aerobic Continuous Training (ACT) on peak VO2, peripheral endothelial function, cardiovascular risk factors, quality of life and safety, in a large multicentre study.MethodsTwo-hundred CAD patients (LVEF >40%, 90% men, mean age 58.4±9.1years) were randomized to a supervised 12-week cardiac rehabilitation programme of three weekly sessions of either AIT (90–95% of peak heart rate (HR)) or ACT (70–75% of peak HR) on a bicycle. Primary outcome was peak VO2; secondary outcomes were peripheral endothelial function, cardiovascular risk factors, quality of life and safety.ResultsPeak VO2 (ml/kg/min) increased significantly in both groups (AIT 22.7±17.6% versus ACT 20.3±15.3%; p-time<0.001). In addition, flow-mediated dilation (AIT+34.1% (range –69.8 to 646%) versus ACT+7.14% (range –66.7 to 503%); p-time<0.001) quality of life and some other cardiovascular risk factors including resting diastolic blood pressure and HDL-C improved significantly after training. Improvements were equal for both training interventions.ConclusionsContrary to earlier smaller trials, we observed similar improvements in exercise capacity and peripheral endothelial function following AIT and ACT in a large population of CAD patients