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 .)

ADHESIVE INTERACTIONS BETWEEN THE TUBE FEET OF A STARFISH, LEPTASTERIAS HEXACTIS, AND SUBSTRATA

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ETS gene fusions in prostate cancer

Chromosomal rearrangements that result in high level expression of ETS gene family members are common events in human prostate cancer. Most frequently, the androgen-activated gene TMPRSS2 is found fused to the ERG gene. Fusions involving ETV1, ETV4 and ETV5 occur less frequently but exhibit greater variability in fusion structure with 12 unique 5' fusion partners identified so far. ETS gene rearrangement seems to be a key event in driving prostate neoplastic development: the rearrangement occurs as an early event and continues to be expressed in metastatic and castration-resistant disease. However, ETS alterations seem insufficient on their own to induce cancer formation. No consistent associations are seen between the presence of ETS alteration and clinical outcome, with the possible exception that duplication of rearranged ERG, reflecting aneuploidy, is associated with poor outcome. Thus, factors other than ERG gene status may be the major determinants of poor clinical outcome. Expression signatures of prostate cancers containing the TMPRSS2-ERG fusion suggest involvement of beta-estradiol signaling, and reveal higher levels of expression of HDAC1 and ion channel genes when compared to cancers that lack the rearrangement. These observations suggest new therapeutic possibilities for patients harboring ETS gene fusions

Intercomparison of instruments for tropospheric measurements using differential optical absorption spectroscopy

The results of an intercomparison campaign of eight different long path UV-visible DOAS instruments measuring NO2, O3 and SO2 concentrations in a moderately polluted urban site are presented. For effective optical path lengths of 230 and 780 m the overall spread of these measurements (± 1 σ) are 5 x 1010, 6 x 1010 and 1 x 1010 molec·cm-3 (2.0, 2.4, and 0.4 ppb) for these molecules respectively when all instruments used a common set of absorption cross sections. The remaining differences are not completely random and the systematic differences are attributed to the different retrieval methods used for each instrument.info:eu-repo/semantics/publishe

Abstracts of the 6th FECS Conference 1998 Lectures

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