Dryland pasture improvement given climatic risk

International audienc

Noninvasive Plaque Imaging to Accelerate Coronary Artery Disease Drug Development

Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque. Such distinct phenotypes reflect different pathophysiologic pathways and are associated with different risks for acute ischemic events. Noninvasive coronary imaging techniques, such as computed tomography, positron emission tomography, and coronary magnetic resonance imaging, have major potential to accelerate cardiovascular drug development, which has been affected by the high costs and protracted timelines of cardiovascular outcome trials. This may be achieved through enrichment of high-risk phenotypes with higher event rates or as primary end points of drug efficacy, at least in phase 2 trials, in a manner historically performed through intravascular coronary imaging studies. Herein, we provide a comprehensive review of the current technology available and its application in clinical trials, including implications for sample size requirements, as well as potential limitations. In its effort to accelerate drug development, the US Food and Drug Administration has approved surrogate end points for 120 conditions, but not for CAD. There are robust data showing the beneficial effects of drugs, including statins, on CAD progression and plaque stabilization in a manner that correlates with established clinical end points of mortality and major adverse cardiovascular events. This, together with a clear mechanistic rationale for using imaging as a surrogate CAD end point, makes it timely for CAD imaging end points to be considered. We discuss the importance of global consensus on these imaging end points and protocols and partnership with regulatory bodies to build a more informed, sustainable staged pathway for novel therapies.Gemma A. Figtree ... Peter J. Psaltis ... Stephen J. Nicholls ... et al

Incivility on Diaoyu Island sovereignty in Tianya Club

Online discussion boards are an increasingly popular mode of public engagement with political and social issues. This case study examines data drawn from online debates on a discussion board regarding a historical dispute between China and Japan since 1895. 1 This research explores how incivility, a concept developed by western scholars and applied to western communication patterns, can be applied to a Chinese cultural context while also considering the characteristics of emotional responses to the specific issue in the forum. Prior research has demonstrated that, due to the absence of a gatekeeper on such forums who would filter or edit content for public consumption, discussion of prominent issues can get heated without a gatekeeper. A textual analysis of incivility found that fear and disgust were not typical emotional responses to incivility among the members of the forum. On the contrary, 'support' was the most identified emotional response in this particular case. In conclusion, cultural context, characteristics of an issue, and characteristics of a particular topic are all important factors that affect 'incivility' and 'emotional response' in online comments on Diaoyu Island Sovereignty on Tianya Club