Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Calculation of Wave Attenuation Due to Friction and Shoaling: An Evaluation

Source: https://erdc-library.erdc.dren.mil/jspui/An evaluation of the Bretschneider and Reid (1954) technique for calculating wave attenuation due to friction and shoaling is presented. Data used in this evaluation were collected at CT.RC' s Field Research Facility (FRF), Duck, North Carolina. The results, using Kamphuis' (1975) friction factor diagram, show slightly underpredicted wave heights with an average deviation of 6 percent. Poor correlation with observed wave heights is illustrated when hot tom contours are not straight and parallel, indicating the presence of other mechanisms

Energy Losses of Waves in Shallow Water

Source: https://erdc-library.erdc.dren.mil/jspui/This report presents a method for predicting nearshore significant wave height given the straight-line fetch length, the windspeed, and the nearshore water depth. The prediction curves were generated by numerically propagating offshore JONSWAP spectra shoreward while applying shoaling and wave steepness limitation criteria to each spectral component. Example problems are included

The Elevation and Duration of Wave Crests

Source: https://erdc-library.erdc.dren.mil/jspui/The stream-function wave theory of Dean (1974) is used together with monochromatic and irregular laboratory wave data to develop methods for estimating the elevation and duration of wave crests. The resulting prediction techniques are applied to a wide range of wave conditions measured at CERC's Field Research Facility in Duck, North Carolina, and are shown to give reliable and often conservative estimates of crest elevation. The techniques presented in this report can be used for both nonbreaking and breaking wave conditions

Beach Nourishment Project Response and Design Evaluation: Ocean City Maryland. Report 1, 1988-1992

Source: https://erdc-library.erdc.dren.mil/jspui/Detailed monitoring of the performance of a two-phase beach nourishment project has provided valuable information on beach fill behavior and long-term response of a beach fill to prevailing coastal processes. The Atlantic Coast of Maryland (Ocean City) Shoreline Protection Project began with placement of a recreational beach by the State of Maryland during the summer of 1988. Within three months of placement, four storms impacted the area. Recovery was monitored for an additional two years. In the summers of 1990 and 1991, additional fill material including a storm protection dune was placed by the U.S. Army Corps of Engineers as a second phase for the purpose of storm protection. Within a year of the first placement, two large storms impacted the project. Initial recovery was also documented. Project monitoring included 12 profile survey lines, sediment collection, and placement of two dedicated wave gauges. The beach nourishment project performed well in protecting the beachfront infrastructure of Ocean City from storm damage. The fill material was eroded from the foreshore after the major storms of 1989 and 1991/92, but could be accounted for in the nearshore between the shoreline and closure. Representative profile survey locations show the differential behavior of the fill controlled by nearshore bathymetric variability along the project length. The 37th Street location represents the flatter, bar/trough type profile typical of the southern portion of the fill. Localized "hot spots" of erosion occurred in areas where a shoal system attaches to the shoreface, as shown at 81st Street. The erosion pattern associated with these shoals was probably produced by wave convergence and divergence over these features. Analysis of sediment characteristics of samples collected during the State fill project showed the influence of the fill material on the native beach and the change in sorting after the passage of four storms. Composites were constructed of the foreshore and nearshore samples to account for cross-shore variability in grain size distribution. The coarsest foreshore and finest nearshore composite fill material was found in the northern end of the project, with the opposite found to the south. Storm impact placed coarse foreshore lag material at the erosional 81st Street location and finer material at the more stable 37th Street location. After 9 months, the fill material was taking on the characteristics of the pre-fill native beach