Inflammatory Mechanisms in Atherosclerosis

Atherosclerosis is a disease of chronic inflammation, characterized by a dysfunctional interplay between the immune apparatus and lipids. Immune cells, as well as nonimmune cells, drive plaque inflammation through a complex crosstalk of inflammatory mediators. The cells are activated by risk factor–induced triggers, which are present in the circulation and in the vessel wall, such as shear stress, oxidized lipoproteins and oxidative stress. Without relief from risk factors, the activation of inflammatory processes persists, resulting in a chronic nonresolving inflammation. Inflammation is associated with severity of disease, and complex lesions, which are prone to rupture and cause acute events, are characterized by extensive inflammation. Thus, inflammation is an active driver of atherosclerotic plaque development and a risk factor for atherosclerotic events. It is therefore of utmost importance to understand the mechanisms behind these inflammatory processes and to be able to develop new diagnostics and treatment modalities for atherosclerotic disorders. This chapter provides a brief overview of the most important inflammatory players and processes during atherosclerotic plaque development and of possible therapeutic targets to combat atherosclerotic disease

Regional frequency analysis of short duration rainfall extremes using gridded daily rainfall data as co-variate

A regional partial duration series (PDS) model is applied for estimation of intensity duration frequency relationships of extreme rainfalls in Denmark. The model uses generalised least squares regression to relate the PDS parameters to gridded rainfall statistics from a dense network of rain gauges with daily measurements. The Poisson rate is positively correlated to the mean annual precipitation for all durations considered (1 min to 48 hours). The mean intensity can be assumed constant over Denmark for durations up to 1 hour. For durations larger than 1 hour, the mean intensity is significantly correlated to the mean extreme daily precipitation. A Generalised Pareto distribution with a regional constant shape parameter is adopted. Compared to previous regional studies in Denmark, a general increase in extreme rainfall intensity for durations up to 1 hour is found, whereas for larger durations both increases and decreases are seen. A subsample analysis is conducted to evaluate the impacts of non-stationarities in the rainfall data. The regional model includes the non-stationarities as an additional source of uncertainty, together with sampling uncertainty and uncertainty caused by spatial variability.</jats:p