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 .)

Marketing imperative or cultural challenge? Embedding widening participation in the further education sector

The government's widening participation agenda places financial imperatives on further education (FE) sector colleges to re-focus their institutional vision and their marketing strategy. At first sight widening participation may be seen as essentially a marketing issue, with two key challenges. Facilitating choice involves enabling an engagement with learning for those who have considered FE but have rejected it because of economic, social, cultural or community barriers. Increasing demand requires colleges to reach out to those for whom engagement with learning has traditionally never been part of their lifestyle horizons. Both are new, but recognisable, marketing objectives which colleges can address. Pursuing traditional FE marketing models based simply on ‘selling’ and a functional view of marketing is destined for failure, however, for widening participation is inherently a challenge to internal institutional culture that requires colleges to change fundamentally their modus operandi, their view of the world and their values. This article explores in the context of FE the relationship between widening participation as a concept and policy, the developing marketing perspective of institutions, and the emerging cultural challenges that face senior managers in colleges. Drawing on case study evidence from a number of FE colleges the article examines how far colleges are responding to this ideological and management imperative. The article concludes that widening participation is firmly established as both a moral and strategic imperative at senior level in FE. However, there is not yet much evidence of this culture permeating more widely through institutions because of the dominance of a project view of widening participation and limited awareness of the complexity of needs and wants in the diverse group of communities that are currently non-participants in FE

The presenilin-2 loop peptide perturbs intracellular Ca2+ homeostasis and accelerates apoptosis

In cells undergoing apoptosis, a 22-amino-acid presenilin-2-loop peptide (PS2-LP, amino acids 308-329 in presenilin-2) is generated through cleavage of the carboxyl-terminal fragment of presenilin-2 by caspase-3. The impact of PS2-LP on the progression of apoptosis, however, is not known. Here we show that PS2-LP is a potent inducer of the mitochondrial-dependent cell death pathway when transduced as a fusion protein with HIV-TAT. Biochemical and functional studies demonstrate that TAT-PS2-LP can interact with the inositol 1,4,5-trisphosphate receptor and activate Ca2+ release from the endoplasmic reticulum. These results indicate that PS2-LP-mediated alteration of intracellular Ca2+ homeostasis may be linked to the acceleration of apoptosis. Therefore, targeting the function of PS2-LP could provide a useful therapeutic tool for the treatment of cancer and degenerative diseases. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.link_to_subscribed_fulltex

A novel lifecycle model for Web-based application development in small and medium enterprises

From the issue entitled "Focal Theme: Digital Manufacturing TechnologySoftware engineering's lifecycle models have proven to be very important for traditional software development. However, can these models be applied to the development of Web-based applications as well? In recent years, Web-based applications have become more and more complicated and a lot of efforts have been placed on introducing new technologies such as J2EE, PhP, and .NET, etc., which have been universally accepted as the development technologies for Web-based applications. However, there is no universally accepted process model for the development of Web-based applications. Moreover, shaping the process model for small medium-sized enterprises (SMEs), which have limited resources, has been relatively neglected. Based on our previous work, this paper presents an expanded lifecycle process model for the development of Web-based applications in SMEs. It consists of three sets of processes, i.e., requirement processes, development processes, and evolution processes. Particularly, the post-delivery evolution processes are important to SMEs to develop and maintain quality web applications with limited resources and time