Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial†

Aim High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. Objective To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). Design and setting A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion. Patients Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Intervention Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. Main outcome measures The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. Results The nominal change in the total atheroma volume (adjusted means) was −2.71, −3.13, −1.50, and −3.05 mm3 with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, −0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was −0.022, −0.036, −0.022, and −0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was −0.51, 2.65, 0.71, and −0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. Conclusion CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2; Trial registration number: NCT0120183

The relationship between subtypes of depression and cardiovascular disease: a systematic review of biological models

A compelling association has been observed between cardiovascular disease (CVD) and depression, suggesting individuals with depression to be at significantly higher risk for CVD and CVD-related mortality. Systemic immune activation, hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, arterial stiffness and endothelial dysfunction have been frequently implicated in this relationship. Although a differential epidemiological association between CVD and depression subtypes is evident, it has not been determined if this indicates subtype specific biological mechanisms. A comprehensive systematic literature search was conducted using PubMed and PsycINFO databases yielding 147 articles for this review. A complex pattern of systemic immune activation, endothelial dysfunction and HPA axis hyperactivity is suggestive of the biological relationship between CVD and depression subtypes. The findings of this review suggest that diagnostic subtypes rather than a unifying model of depression should be considered when investigating the bidirectional biological relationship between CVD and depression. The suggested model of a subtype-specific biological relationship between depression and CVDs has implications for future research and possibly for diagnostic and therapeutic processes

Situation calculus-based programs for representing and reasoning about game structures

International Conference on Principles of Knowledge Representation and Reasoning (KR

Synchronous games in the situation calculus

We develop a situation calculus-based account of multi-player synchronous games. These are represented as action theories called situation calculus synchronous game structures (SCSGSs) that involve a single action tick whose effects depend on the combination of moves chosen by the players. Properties of games, e.g., winning conditions, playability, weak and strong winnability, etc. can be expressed in a first-order variant of alternating-time mu-calculus. Computationally effective verification can be performed. SCSGSs can be viewed as a variant of the Game Description Language (CDL) where states are represented by first-order theories. Copyright © 2015, International Foundation for Autonomous Agents and Multiagent Systems (www.ifaamas.org). All rights reserved

Entropy-based image merging

Spacecraft docking using vision is a challenging task. Not least among the problems encountered is the need to visually localize the docking target. Here we consider the task of adapting the local illumination to assist in this docking. An online approach is developed that combines images obtained under different exposure and lighting conditions into a single image upon which docking decisions can be made. This method is designed to be used within an intelligent controller that automatically adjusts lighting and image acquisition in order to obtain the “best” possible composite view of the target for further image processing. Keywords: Image Entropy, High Dynamic Range.

Ability and Knowing How in the Situation Calculus

Most agents can acquire information about their environments as they operate. A good plan for such an agent is one that not only achieves the goal, but is also executable, i.e., ensures that the agent has enough information at every step to know what to do next. In this paper, we present a formal account of what it means for an agent to know how to execute a plan and to be able to achieve a goal. Such a theory is a prerequisite for producing specifications of planners for agents that can acquire information at run time. It is also essential to account for cooperation among agents. Our account is more general than previous proposals, correctly handles programs containing loops, and incorporates a solution to the frame problem. It can also be used to prove programs containing sensing actions correct. © 2000 Kluwer Academic Publishers