Regional forecasting with global atmospheric models; Fourth year report

The scope of the report is to present the results of the fourth year`s work on the atmospheric modeling part of the global climate studies task. The development testing of computer models and initial results are discussed. The appendices contain studies that provide supporting information and guidance to the modeling work and further details on computer model development. Complete documentation of the models, including user information, will be prepared under separate reports and manuals

Modelling the climate of the last millennium: what causes the differences between simulations?

An ensemble of simulations performed with a coarse resolution 3-D climate model driven by various combinations of external forcing is used to investigate possible causes for differences noticed in two recent simulations of the climate of the past millennium using General Circulation Models (GCMs). Our results strongly suggest that differences in sensitivity (equilibrium and transient climate response) could be responsible for temperature changes that differ by more than a factor of two between two models. In addition, the spin-up procedure could explain some differences between the simulations during the first centuries of the second millennium. The choice of the forcing reconstruction is found to play a smaller role for the differences in the simulated climate, in the model configurations analyzed here. Furthermore, at decadal scale, internal climate variability can mask the differences associated with different forcing reconstructrions. Copyright 2005 by the American Geophysical Union

Regional forecasting with global atmospheric models; Fourth year report

The scope of the report is to present the results of the fourth year`s work on the atmospheric modeling part of the global climate studies task. The development testing of computer models and initial results are discussed. The appendices contain studies that provide supporting information and guidance to the modeling work and further details on computer model development. Complete documentation of the models, including user information, will be prepared under separate reports and manuals

Effects of liraglutide on cardiovascular outcomes in type 2 diabetes patients with and without baseline metformin use: Post hoc analyses of the LEADER trial

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) reduce cardiovascular (CV) events among patients with type 2 diabetes and high CV risk. Because consensus professional society recommendations endorse metformin as the first-line medication for type 2 diabetes, the CV efficacy of GLP-1RAs has primarily been studied with background metformin therapy. However, the European Society of Cardiology now recommends GLP-1RAs as a first-line type 2 diabetes treatment for patients at high CV risk. These discordant recommendations raise the question of how background metformin might influence the CV benefits of GLP-1RAs. Using data from the LEADER trial,we sought to answer this question by exploring possible heterogeneity in the CV efficacy of liraglutide related to baseline metformin treatment

Geological controls on the geometry of incised-valley fills: Insights from a global dataset of late-Quaternary examples

Incised valleys that develop due to relative sea-level change are common features of continental shelves and coastal plains. Assessment of the factors that control the geometry of incised-valley fills has hitherto largely relied on conceptual, experimental or numerical models, else has been grounded on case studies of individual depositional systems. Here, a database-driven statistical analysis of 151 late-Quaternary incised-valley fills has been performed, the aim being to investigate the geological controls on their geometry. Results of this analysis have been interpreted with consideration of the role of different processes in determining the geometry of incised-valley fills through their effect on the degree and rate of river incision, and on river size and mobility. The studied incised-valley fills developed along active margins are thicker and wider, on average, than those along passive margins, suggesting that tectonic setting exerts a control on the geometry of incised-valley fills, likely through effects on relative sea-level change and river behaviour, and in relation to distinct characteristics of basin physiography, water discharge and modes of sediment delivery. Valley-fill geometry is positively correlated with the associated drainage-basin size, confirming the dominant role of water discharge. Climate is also inferred to exert a potential control on valley-fill dimensions, possibly through modulations of temperature, peak precipitation, vegetation and permafrost, which would in turn affect water discharge, rates of sediment supply and valley-margin stability. Shelves with slope breaks that are currently deeper than 120 m contain incised-valley fills that are thicker and wider, on average, than those hosted on shelves with breaks shallower than 120 m. No correlation exists between valley-fill thickness and present-day coastal-prism convexity, which is measured as the difference in gradient between lower coastal plains and inner shelves. These findings challenge some concepts embedded in sequence stratigraphic thinking, and have significant implications for analysis and improved understanding of source-to-sink sediment route-ways, and for attempting predictions of the occurrence and characteristics of hydrocarbon reservoirs

Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension

Objectives To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks. Methods Adults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or placebo every 4 weeks for 24 weeks (NCT02526160). Thereafter, all subjects received burosumab every 4 weeks until week 96. PROs were measured using the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), and ambulatory function was measured with the 6 min walk test (6MWT). Results Subjects (N=134) were randomised to burosumab (n=68) or placebo (n=66) for 24 weeks. At baseline, subjects experienced pain, stiffness, and impaired physical and ambulatory function. At week 24, subjects receiving burosumab achieved statistically significant improvement in some BPI-SF scores, BFI worst fatigue (average and greatest) and WOMAC stiffness. At week 48, all WOMAC and BPI-SF scores achieved statistically significant improvement, with some WOMAC and BFI scores achieving meaningful and significant change from baseline. At week 96, all WOMAC, BPI-SF and BFI achieved statistically significant improvement, with selected scores in all measures also achieving meaningful change. Improvement in 6MWT distance and percent predicted were statistically significant at all time points from 24 weeks. Conclusions Adults with XLH have substantial burden of disease as assessed by PROs and 6MWT. Burosumab treatment improved phosphate homoeostasis and was associated with a steady and consistent improvement in PROs and ambulatory function. Trial registration number NCT02526160

Regional forecasting with global atmospheric models; Final report

The purpose of the project was to conduct model simulations for past and future climate change with respect to the proposed Yucca Mtn. repository. The authors report on three main topics, one of which is boundary conditions for paleo-hindcast studies. These conditions are necessary for the conduction of three to four model simulations. The boundary conditions have been prepared for future runs. The second topic is (a) comparing the atmospheric general circulation model (GCM) with observations and other GCMs; and (b) development of a better precipitation data base for the Yucca Mtn. region for comparisons with models. These tasks have been completed. The third topic is preliminary assessments of future climate change. Energy balance model (EBM) simulations suggest that the greenhouse effect will likely dominate climate change at Yucca Mtn. for the next 10,000 years. The EBM study should improve rational choice of GCM CO{sub 2} scenarios for future climate change

Regional forecasting with global atmospheric models; Third year report

This report was prepared by the Applied Research Corporation (ARC), College Station, Texas, under subcontract to Pacific Northwest Laboratory (PNL) as part of a global climate studies task. The task supports site characterization work required for the selection of a potential high-level nuclear waste repository and is part of the Performance Assessment Scientific Support (PASS) Program at PNL. The work is under the overall direction of the Office of Civilian Radioactive Waste Management (OCRWM), US Department of Energy Headquarters, Washington, DC. The scope of the report is to present the results of the third year`s work on the atmospheric modeling part of the global climate studies task. The development testing of computer models and initial results are discussed. The appendices contain several studies that provide supporting information and guidance to the modeling work and further details on computer model development. Complete documentation of the models, including user information, will be prepared under separate reports and manuals