A double continuum hydrological model for glacier applications

Peer reviewedPublisher PD

Seasonal variations in Greenland Ice Sheet motion : Inland extent and behaviour at higher elevations

Peer reviewedPreprin

Pharmacist intervention in primary care to improve outcomes in patients with left ventricular systolic dysfunction

<b>Background</b> Meta-analysis of small trials suggests that pharmacist-led collaborative review and revision of medical treatment may improve outcomes in heart failure.<p></p> <b>Methods and results</b> We studied patients with left ventricular systolic dysfunction in a cluster-randomized controlled, event driven, trial in primary care. We allocated 87 practices (1090 patients) to pharmacist intervention and 87 practices (1074 patients) to usual care. The intervention was delivered by non-specialist pharmacists working with family doctors to optimize medical treatment. The primary outcome was a composite of death or hospital admission for worsening heart failure. This trial is registered, number ISRCTN70118765. The median follow-up was 4.7 years. At baseline, 86% of patients in both groups were treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. In patients not receiving one or other of these medications, or receiving less than the recommended dose, treatment was started, or the dose increased, in 33.1% of patients in the intervention group and in 18.5% of the usual care group [odds ratio (OR) 2.26, 95% CI 1.64–3.10; P< 0.001]. At baseline, 62% of each group were treated with a β-blocker and the proportions starting or having an increase in the dose were 17.9% in the intervention group and 11.1% in the usual care group (OR 1.76, 95% CI 1.31–2.35; P< 0.001). The primary outcome occurred in 35.8% of patients in the intervention group and 35.4% in the usual care group (hazard ratio 0.97, 95% CI 0.83–1.14; P = 0.72). There was no difference in any secondary outcome.<p></p> <b>Conclusion</b> A low-intensity, pharmacist-led collaborative intervention in primary care resulted in modest improvements in prescribing of disease-modifying medications but did not improve clinical outcomes in a population that was relatively well treated at baseline

Field-calibrated model of melt, refreezing, and runoff for polar ice caps : Application to Devon Ice Cap

Acknowledgments R.M.M. was supported by the Scottish Alliance for Geoscience, Environment and Society (SAGES). The field data collection contributed to the validation of the European Space Agency Cryosat mission and was supported by the Natural Sciences and Engineering Research Council, Canada, the Meteorological Service of Canada (CRYSYS program), the Polar Continental Shelf Project (an agency of Natural Resources Canada), and by UK Natural Environment Research Council consortium grant NER/O/S/2003/00620. Support for D.O.B. was provided by the Canadian Circumpolar Institute and the Climate Change Geoscience Program, Earth Sciences Sector, Natural Resources Canada (ESS contribution 20130371). Thanks are also due to the Nunavut Research Institute and the communities of Resolute Bay and Grise Fjord for permission to conduct fieldwork on Devon Ice Cap. M.J. Sharp, A. Gardner, F. Cawkwell, R. Bingham, S. Williamson, L. Colgan, J. Davis, B. Danielson, J. Sekerka, L. Gray, and J. Zheng are thanked for logistical support and field assistance during the data collection. We thank Ruzica Dadic, two other anonymous reviewers, and the Editor, Bryn Hubbard, for their helpful comments on an earlier version of this paper and which resulted in significant improvements.Peer reviewedPublisher PD

Serotonin signaling through the 5-HT1B receptor and NADPH oxidase 1 in pulmonary arterial hypertension

Objective: Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesise that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase-derived ROS generation and reduced Nrf-2 anti-oxidant systems, promoting vascular injury. Approach and Results: HPASMCs from controls and PAH patients, and PASMCs from Nox1-/- mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT1B receptor and NADPH oxidase 1 (Nox1). Markers of fibrosis were also determined. The pathophysiological significance of our findings was examined in vivo in serotonin transporter overexpressing (SERT+) female mice, a model of pulmonary hypertension (PH). We confirmed serotonin increased superoxide and H2O2 production in these cells. For the first time, we show that serotonin increased oxidized protein tyrosine phosphatases and peroxiredoxin-SO3H and decreased Nrf-2 and catalase activity in hPASMCs. ROS generation was exaggerated, and dependent on c-Src, 5-HT1B receptor and the serotonin transporter in PAH-hPASMCs. Proliferation and extracellular matrix remodeling were exaggerated in PAH-hPASMCs and dependent on 5-HT1B receptor signaling and Nox1, confirmed in PASMCs from Nox1-/- mice. In SERT+ mice, SB216641, a 5-HT1B receptor antagonist, prevented development of PH in a ROS-dependent manner. Conclusions: Serotonin can induce c-Src-regulated Nox1-induced ROS and Nrf-2 dysregulation, contributing to increased post-translational oxidative modification of proteins, activation of redox-sensitive signaling pathways in hPASMCs; associated with mitogenic responses. 5-HT1B receptors contribute to experimental PH by inducing lung ROS production. Our results suggest 5-HT1B receptor-dependent c-Src-Nox1-pathways contribute to vascular remodeling in PAH

Minibatch training of neural network ensembles via trajectory sampling

Most iterative neural network training methods use estimates of the loss function over small random subsets (or minibatches) of the data to update the parameters, which aid in decoupling the training time from the (often very large) size of the training datasets. Here, we show that a minibatch approach can also be used to train neural network ensembles (NNEs) via trajectory methods in a highly efficent manner. We illustrate this approach by training NNEs to classify images in the MNIST datasets. This method gives an improvement to the training times, allowing it to scale as the ratio of the size of the dataset to that of the average minibatch size which, in the case of MNIST, gives a computational improvement typically of two orders of magnitude. We highlight the advantage of using longer trajectories to represent NNEs, both for improved accuracy in inference and reduced update cost in terms of the samples needed in minibatch updates.Comment: 11 pages, 4 figures, 1 algorith

The United Kingdom at the polls

De komende parlementsverkiezingen in Groot-Brittanië beloven de spannendste sinds jaren te worden. De BB vond docent Peter Mair bereid zijn licht hierover te laten schijnen

An introduction to the Northern Ireland problem

Peter Mair verzorgt dit jaar namens de vakgroep Politicologie de cursus Grote Mogendheden voor bestuurskundestudenten in hun basisdoctoraal. Eenieder die deze collegereeks volgt zal duidelijk zijn dat hij zich zeer betrokken voelt bij de toestand in Noord-Ierland .Mair is dan ook zelf van Ierse afkomst. Onder begeleiding van professor Daalder schreef hij het proefschrift 'Changing the Irish Party System'. Peter Mair geeft hier een eerste schets van de problemen