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 .)

Downregulation of the (1)- and (1)-subunit of sGC in Arterial Smooth Muscle Cells of OPSCC Is HPV-Independent

The nitric oxide (NO)-sensitive soluble guanylyl cyclase (sGC) is a heterodimeric enzyme with an and subunit. NO binds to heme of the (1)-subunit of sGC, activates the enzyme in the reduced heme iron state in vascular smooth muscle cells (VSMCs), and generates cGMP-inducing vasodilatation and suppression of VSMC proliferation. In the complex tumor milieu with higher levels of reactive oxygen species (ROS), sGC heme iron may become oxidized and insensitive to NO. To change sGC from an NO-insensitive to NO-sensitive state or NO-independent manner, protein expression of sGC in VSMC is required. Whether sGC(11) exists at the protein level in arterial VSMCs of oropharyngeal squamous cell carcinoma (OPSCC) is unknown. In addition, whether differences in the genetic profile between human papillomavirus (HPV)-positive and HPV-negative OPSCC contributes to the regulation of sGC(11) is unclear. Therefore, we compared the effects of HPV-positive and HPV-negative OPSCC on the expression of sGC(11) in arterial VSMCs from tumor-free and tumor-containing regions of human tissue sections using quantitative immunohistochemistry. In comparison to the tumor-free region, we found a decrease in expression of both (1)- and (1)-subunits in the arterial VSMC layer of the tumor-containing areas. The OPSCC-induced significant downregulation of the (1)- and (1)-subunits of sGC in arterial VSMC was HPV-independent. We conclude that the response of sGC to NO in tumor arterial VSMCs may be impaired by oxidation of the heme of the (1)-subunit, and thus, (1)- and (1)-subunits of sGC could be targeted to degradation under oxidative stress in OPSCC in an HPV-independent manner. The degradation of sGC(11) in VSMCs may result in increased proliferation of VSMCs, promoting tumor arteriogenesis in OPSCC. This can be interrupted by preserving the active heterodimer sGC(11) in arterial VSMCs

Status of Four-Junction Cell Development at Fraunhofer ISE

Four-junction solar cells are being developed for space applications as they promise higher efficiencies compared to the present GaInP/GaInAs/Ge triple-junction industry standard. There are multiple technological routes to achieve four-junction cells with the ideal bandgap combination of 1.9 eV, 1.4 eV 1.05 eV and 0.7 eV. This includes metamorphic growth concepts and direct semiconductor wafer bonded technology. All cell designs have their specific advantages and challenges. Therefore, at Fraunhofer ISE a plurality of different four-junction cell concepts is under investigation. The current status of the development and a discussion of so far achieved characteristics are presented in this work

Status of four-junction cell development at Fraunhofer ISE

Four-junction solar cells are being developed for space applications as they promise higher efficiencies compared to the present GaInP/GaInAs/Ge triple-junction industry standard. There are multiple technological routes to achieve four-junction cells with the ideal bandgap combination of 1.9 eV, 1.4 eV 1.05 eV and 0.7 eV. This includes metamorphic growth concepts and direct semiconductor wafer bonded technology. All cell designs have their specific advantages and challenges. Therefore, at Fraunhofer ISE a plurality of different four-junction cell concepts is under investigation. The current status of the development and a discussion of so far achieved characteristics are presented in this work

Research on multi-junction solar cells at Fraunhofer ISE: Presentation held at CPV 2017, 13th International Conference on Concentrator Photovoltaic Systems, Ottawa, Canada, May 01 - 03, 2017

In this work, we investigated the impact of intensive heat loads on concentrator solar cells assemblies. As test samples, we employed lattice-matched and lattice-mismatched triple-junction solar cells made of GaInP/GaInAs/Ge. The thermal loads were induced by different manners. We used drying cabinets, external power supplies, and a combination of both to achieve maximum test temperatures of 180 °C. For the performance analysis, we utilized flash light solar simulators and an electroluminescence (EL) imaging tool. Our experiments revealed a significant difference depending on the applied manner of heating. The highest impact was observed for the pure heat treatment in drying cabinets. This was particularly visible in the spatial EL images, but also in the IV curves. In contrast, running the concentrator solar cells as forward-biased diodes using an external current supply of 2000 mA, which corresponds to 2000 suns, did not lead to any significant changes in EL and IV curves. However, deformation of the front metallization was observed. In conclusions, pure heat treatment can be considered as a cost-efficient alternative to pinpoint weak points in solar cell receivers

The Role of Workplace Chaplains in Industrial Relations: Evidence from Australia

This paper examines a neglected and largely invisible actor within the field of industrial relations. Taking the case of industrial chaplains in Australian workplaces, it demonstrates that not only do chaplains play an important and independent role in their own right, but that their ostensible neutrality is also used to help achieve the interests of both management and trade unions. The location of chaplains in industrial relations and their need to develop workplace legitimacy accounts for this finding. This suggests that future studies that seek to explore the purpose and activities of new and non-traditional groups in industrial relations will need to place their analyses within the context of more established actors. Copyright Blackwell Publishing Ltd/London School of Economics 2006.