Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Down to the Crust: Chemical and Mineralogical Analysis of Ceramic Surface Encrustations on Bronze Age Ceramics from Békés 103, Eastern Hungary

Békés 103, a primarily Middle Bronze Age (c. 1600–1280 calBC) cemetery and settlement on the Great Hungarian Plain, has been investigated by the BAKOTA project since 2011. Ceramics from the site are covered in dense white concretions, and it has been noted during compositional analyses that these vessels exhibit elevated concentrations of several potentially mobile elements in comparison to vessels from regional tell sites. Here, we use a multimethod (optical mineralogy, FT-IR, XRD, XPS, PXRF, SEM-EDS, and LA-ICP-MS) mineralogical and chemical approach to characterize the composition of surface encrustations on ceramics samples from Békés 103. We also chemically map interior paste composition using LA-ICP-MS to identify potential leaching of mobile elements into or out of vessel bodies. We demonstrate that the surface encrustations are primarily composed of calcite but also contain a variety of other mineral and organic constituents indicative of deposition of soil carbonates, phosphates, nitrates, and other inorganic and organic components. We further document the leaching of several mobile elements into ceramic pastes as well as formation of secondary calcite along void, pore, and temper boundaries. The presence of cremated bone and possibly bone ash in close vicinity to many of the studied vessels may also have contributed to the observed patterns of diagenesis. It is likely that similar post-burial processes might affect ceramics from other sites located in low-lying, seasonally inundated contexts

Down to the Crust: Chemical and Mineralogical Analysis of Ceramic Surface Encrustations on Bronze Age Ceramics from Békés 103, Eastern Hungary

Békés 103, a primarily Middle Bronze Age (c. 1600–1280 calBC) cemetery and settlement on the Great Hungarian Plain, has been investigated by the BAKOTA project since 2011. Ceramics from the site are covered in dense white concretions, and it has been noted during compositional analyses that these vessels exhibit elevated concentrations of several potentially mobile elements in comparison to vessels from regional tell sites. Here, we use a multimethod (optical mineralogy, FT-IR, XRD, XPS, PXRF, SEM-EDS, and LA-ICP-MS) mineralogical and chemical approach to characterize the composition of surface encrustations on ceramics samples from Békés 103. We also chemically map interior paste composition using LA-ICP-MS to identify potential leaching of mobile elements into or out of vessel bodies. We demonstrate that the surface encrustations are primarily composed of calcite but also contain a variety of other mineral and organic constituents indicative of deposition of soil carbonates, phosphates, nitrates, and other inorganic and organic components. We further document the leaching of several mobile elements into ceramic pastes as well as formation of secondary calcite along void, pore, and temper boundaries. The presence of cremated bone and possibly bone ash in close vicinity to many of the studied vessels may also have contributed to the observed patterns of diagenesis. It is likely that similar post-burial processes might affect ceramics from other sites located in low-lying, seasonally inundated contexts