Applying the DORIS Framework: Software-based Modelling for Contextual Development

This paper presents a working example of the use of the Distributed Object-based Real-time Interactive Simulation (DORIS) framework for modelling a bespoke multimedia rich pervasive teaching environment: the Centre for Excellent in Teaching and Learning (CETL) in Creativity at the University of Sussex. The control software for the environment is contextually developed on top of this model

Exercise during hemodialysis does not affect the phenotype or prothrombotic nature of microparticles but alters their proinflammatory function.

Hemodialysis patients have dysfunctional immune systems, chronic inflammation and comorbidity-associated risks of cardiovascular disease (CVD) and infection. Microparticles are biologically active nanovesicles shed from activated endothelial cells, immune cells, and platelets; they are elevated in hemodialysis patients and are associated with chronic inflammation and predictive of CVD mortality in this group. Exercise is advocated in hemodialysis to improve cardiovascular health yet acute exercise induces an increase in circulating microparticles in healthy populations. Therefore, this study aimed to assess acute effect of intradialytic exercise (IDE) on microparticle number and phenotype, and their ability to induce endothelial cell reactive oxygen species (ROS) in vitro. Eleven patients were studied during a routine hemodialysis session and one where they exercised in a randomized cross-over design. Microparticle number increased during hemodialysis (2064-7071 microparticles/μL, P < 0.001) as did phosphatidylserine+ (P < 0.05), platelet-derived (P < 0.01) and percentage procoagulant neutrophil-derived microparticles (P < 0.05), but this was not affected by IDE. However, microparticles collected immediately and 60 min after IDE (but not later) induced greater ROS generation from cultured endothelial cells (P < 0.05), suggesting a transient proinflammatory event. In summary IDE does not further increase prothrombotic microparticle numbers that occurs during hemodialysis. However, given acute proinflammatory responses to exercise stimulate an adaptation toward a circulating anti-inflammatory environment, microparticle-induced transient increases of endothelial cell ROS in vitro with IDE may indicate the potential for a longer-term anti-inflammatory adaptive effect. These findings provide a crucial evidence base for future studies of microparticles responses to IDE in view of the exceptionally high risk of CVD in these patients

The Large-scale Structure of the Halo of the Andromeda Galaxy. II. Hierarchical Structure in the Pan-Andromeda Archaeological Survey

The Pan-Andromeda Archaeological Survey is a survey of >400 square degrees centered on the Andromeda (M31) and Triangulum (M33) galaxies that has provided the most extensive panorama of an L sstarf galaxy group to large projected galactocentric radii. Here, we collate and summarize the current status of our knowledge of the substructures in the stellar halo of M31, and discuss connections between these features. We estimate that the 13 most distinctive substructures were produced by at least 5 different accretion events, all in the last 3 or 4 Gyr. We suggest that a few of the substructures farthest from M31 may be shells from a single accretion event. We calculate the luminosities of some prominent substructures for which previous estimates were not available, and we estimate the stellar mass budget of the outer halo of M31. We revisit the problem of quantifying the properties of a highly structured data set; specifically, we use the OPTICS clustering algorithm to quantify the hierarchical structure of M31's stellar halo and identify three new faint structures. M31's halo, in projection, appears to be dominated by two "mega-structures," which can be considered as the two most significant branches of a merger tree produced by breaking M31's stellar halo into increasingly smaller structures based on the stellar spatial clustering. We conclude that OPTICS is a powerful algorithm that could be used in any astronomical application involving the hierarchical clustering of points. The publication of this article coincides with the public release of all PAndAS data products

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial

Background Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. Methods In this multicentre, open-label, randomised controlled trial, we recruited women aged 18–40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. Findings Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference −0·19%; 95% CI −0·34 to −0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). Interpretation Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use