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

Peer reviewedPreprin

A double continuum hydrological model for glacier applications

Peer reviewedPublisher PD

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

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

Personalised electronic messages to improve sun protection in young adults

The incidence of all skin cancers, including melanoma, continues to rise. It is well known that ultraviolet (UV) radiation is the main environmental risk factor for skin cancer, and excessive exposure at a young age increases the risk of developing skin cancer. The aim of this study was to determine the acceptability and feasibility of delivering sun protection messages via electronic media such as short message services (SMS) to people 18-40 years, and explore factors associated with their acceptability. Overall, 80% of participants agreed that they would like to receive some form of sun protection advice; of these, 20% prefer to receive it via SMS and 42% via email. Willingness to receive electronic messages about the UV index was associated with being unsure about whether a suntanned person would look healthy and greater use of sun protection in the past. Careful attention to message framing and timing of message delivery and focus on short-term effects of sun exposure such as sunburn and skin ageing should increase the acceptability of such messages to young people. We conclude that sun protection messages delivered to young adults via electronic media appear feasible and acceptable

Fluctuations of a Greenlandic tidewater glacier driven by changes in atmospheric forcing : observations and modelling of Kangiata Nunaata Sermia, 1859–present

Acknowledgements. The authors wish to thank Stephen Price, Mauri Pelto, and the anonymous reviewer for their reviews and comments that helped to improve the manuscript. RACMO2.1 data were provided by Jan van Angelen and Michiel van den Broeke, IMAU, Utrecht University. MAR v3.2 data used for runoff calculations were provided by Xavier Fettweis, Department of Geography, University of Liège. The photogrammetric DEM used in Figs. 1 and 3 was provided by Kurt H. Kjær, Centre for GeoGenetics, University of Copenhagen. This research was financially supported by J. M. Lea’s PhD funding, NERC grant number NE/I528742/1. Support for F. M. Nick was provided through the Conoco-Phillips/Lundin Northern Area Program CRIOS project (Calving Rates and Impact on Sea Level).Peer reviewedPublisher PD

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

The puzzle of non-party actors in party democracy: Independents in Ireland

It is an accepted truth that parties are the central political actors in all liberal democracies. This dominance of parties is often considered the logical outcome of rational politicians’ attempts to maximize their utility in terms of votes and policy influence. However, the last twenty years have seen a number of significant Independent (i.e. non-party) actors emerge in more than a few political systems. From an actor-centred point of view, party affiliation can, depending on the particular environment, be rather a liability than an advantage, which has significant implications for the role of non-party actors in face of weakening party democracies. To demonstrate this point, we deliver an account of the rise of Independents in the Irish political system, opposed to the dominant scholarly perspective that tends to consider Independents as an idiosyncrasy. We show that the choice of organizational independence over party affiliation represents a reaction to incentives inherent in the electoral, parliamentary and governmental stages that can disfavour party as the most efficient vehicle for individual goal attainment. This becomes evident when avoiding the misleading comparison between parties as collective bodies with that of Independents as individuals, instead focussing on the respective strategic positions of the individual MPs