The State of Coral Reef Ecosystems of the United States and Pacific Freely Associated States: 2002

Called for by the U.S. Coral Reef Task Force’s (USCRTF) National Action Plan to Conserve Coral Reefs, this is the first biennial report on the condition of coral reefs. It is the scientific baseline for subsequent reports on the health of U.S. coral reef ecosystems that are to be used by NOAA and others to evaluate the efficacy of coral reef conservation and management practices. The National Oceanic and Atmospheric Administration’s National Ocean Service led the development of this report. It was authored by 38 experts and supported by 79 contributors from government agencies and non-governmental organizations across the nation and internationally. Over 100 Task Force members and other notable scientists have reviewed this document

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

Geologic Setting and Ecological Functioning of Coral Reefs in American Samoa

[Chapter Introduction] American Samoa is rich in coral reefs and all islands are more or less fringed by coral reefs. Although structurally not part of the Samoan chain, political American Samoa includes Rose Atoll, a true atoll, and Swains Island. The coral reefs of American Samoa are integrated into a national protected areas system with the National Park of American Samoa (US Department of Interior) managing some coral reefs on the north coast of Tutuila near Vatia and along the shores of southern Ofu, and southeastern Ta’u, while the National Marine Sanctuary Program (US Department of Commerce) manages Fagatele Bay. Although debated among historians, many believe that the Samoan Islands were originally inhabited as early as 1000 bc. Thus, the division between American and independent Samoa is very recent and pre-Western history of both Samoan groups is inextricably linked. The Manu’a Islands (Ofu, Olosega, Ta’u ) of American Samoa have one of the oldest histories of Polynesia, and the Tuimanu’a title, formerly held by the highest chief of the Manu’a islands, is considered the oldest chiefly title. The title’s name is obviously derived from the islands’ name and its prestige is because the Manu’a Islands were, at least according to Samoan oral tradition, the first islands settled in Polynesia. During the Tongan occupation of Samoa, Manu’a was the only island group that remained independent because of the familial relationship between the Tuimanu’a and the Tuitonga, who was descended from a former Tuimanu’a. The islands of Tutuila and Aunu’u were culturally connected to Upolu Island in what is now independent Samoa. Still today, all the Samoan Islands are politically connected through the chieftain system and through family connections.https://nsuworks.nova.edu/occ_facbooks/1135/thumbnail.jp

National Oceanic and Atmospheric Administration Report 27

Report on the status review of 83 species of coral in relation to their status as threatened or endangered based on the criteria set by the Endangered Species Act

Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition

The role of KRAS, when activated through canonical mutations, has been well established in cancer1. Here we explore a secondary means of KRAS activation in cancer: focal high-level amplification of the KRAS gene in the absence of coding mutations. These amplifications occur most commonly in esophageal, gastric and ovarian adenocarcinomas2,3,4. KRAS-amplified gastric cancer models show marked overexpression of the KRAS protein and are insensitive to MAPK blockade owing to their capacity to adaptively respond by rapidly increasing KRAS–GTP levels. Here we demonstrate that inhibition of the guanine-exchange factors SOS1 and SOS2 or the protein tyrosine phosphatase SHP2 can attenuate this adaptive process and that targeting these factors, both genetically and pharmacologically, can enhance the sensitivity of KRAS-amplified models to MEK inhibition in both in vitro and in vivo settings. These data demonstrate the relevance of copy-number amplification as a mechanism of KRAS activation, and uncover the therapeutic potential for targeting of these tumors through combined SHP2 and MEK inhibition