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

Niche Dimension as an Emergent Property of Food-Web Structure

Ecosystems are often described as food webs: networks in which nodes are species and links stand for predation. The research in the field of these ecological networks is becoming more and more relevant given the increasing pressure the ecosystems are facing, which makes the study of their topology specially interesting due to its interconnection with the dynamical processes taking place in it. The concept of the ecological niche of a species has been discussed for a long time. The term was originally used to refer to a species habitat or ecological role. It was then re-defined by Hutchinson as a position in a multi-dimensional hyperspace - each dimension being some biologically relevant magnitude [2].</p

The next generation of scenarios for climate change research and assessment

Advances in the science and observation of climate change are providing a clearer understanding of the inherent variability of Earth's climate system and its likely response to human and natural influences. The implications of climate change for the environment and society will depend not only on the response of the Earth system to changes in radiative forcings, but also on how humankind responds through changes in technology, economies, lifestyle and policy. Extensive uncertainties exist in future forcings of and responses to climate change, necessitating the use of scenarios of the future to explore the potential consequences of different response options. To date, such scenarios have not adequately examined crucial possibilities, such as climate change mitigation and adaptation, and have relied on research processes that slowed the exchange of information among physical, biological and social scientists. Here we describe a new process for creating plausible scenarios to investigate some of the most challenging and important questions about climate change confronting the global community

The seasonal cycle in coupled ocean-atmosphere general circulation models

We examine the seasonal cycle of near-surface air temperature simulated by 17 coupled ocean-atmosphere general circulation models participating in the Coupled Model Intercomparison Project (CMIP). Nine of the models use ad hoc “flux adjustment” at the ocean surface to bring model simulations close to observations of the present-day climate. We group flux-adjusted and non-flux-adjusted models separately and examine the behavior of each class. When averaged over all of the flux-adjusted model simulations, near-surface air temperature falls within 2?K of observed values over the oceans. The corresponding average over non-flux-adjusted models shows errors up to ?6?K in extensive ocean areas. Flux adjustments are not directly applied over land, and near-surface land temperature errors are substantial in the average over flux-adjusted models, which systematically underestimates (by ?5?K) temperature in areas of elevated terrain. The corresponding average over non-flux-adjusted models forms a similar error pattern (with somewhat increased amplitude) over land. We use the temperature difference between July and January to measure seasonal cycle amplitude. Zonal means of this quantity from the individual flux-adjusted models form a fairly tight cluster (all within ?30% of the mean) centered on the observed values. The non-flux-adjusted models perform nearly as well at most latitudes. In Southern Ocean mid-latitudes, however, the non-flux-adjusted models overestimate the magnitude of January-minus-July temperature differences by ?5?K due to an overestimate of summer (January) near-surface temperature. This error is common to five of the eight non-flux-adjusted models. Also, over Northern Hemisphere mid-latitude land areas, zonal mean differences between July and January temperatures simulated by the non-flux-adjusted models show a greater spread (positive and negative) about observed values than results from the flux-adjusted models. Elsewhere, differences between the two classes of models are less obvious. At no latitude is the zonal mean difference between averages over the two classes of models greater than the standard deviation over models. The ability of coupled GCMs to simulate a reasonable seasonal cycle is a necessary condition for confidence in their prediction of long-term climatic changes (such as global warming), but it is not a sufficient condition unless the seasonal cycle and long-term changes involve similar climatic processes. To test this possible connection, we compare seasonal cycle amplitude with equilibrium warming under doubled atmospheric carbon dioxide for the models in our data base. A small but positive correlation exists between these two quantities. This result is predicted by a simple conceptual model of the climate system, and it is consistent with other modeling experience, which indicates that the seasonal cycle depends only weakly on climate sensitivity