Purpose To present the current understanding of age-related macular degeneration (AMD) pathogenesis, based on clinical evidence, epidemiologic data, histopathologic examination, and genetic data; to provide an update on current and emerging therapies; and to propose an integrated model of the pathogenesis of AMD. Design Review of published clinical and experimental studies. Methods Analysis and synthesis of clinical and experimental data. Results We are closer to a complete understanding of the pathogenesis of AMD, having progressed from clinical observations to epidemiologic observations and clinical pathologic correlation. More recently, modern genetic and genomic studies have facilitated the exploration of molecular pathways. It seems that AMD is a complex disease that results from the interaction of genetic susceptibility with aging and environmental factors. Disease progression also seems to be driven by a combination of genetic and environmental factors. Conclusions Therapies based on pathophysiologic features have changed the paradigm for treating neovascular AMD. With improved understanding of the underlying genetic susceptibility, we can identify targets to halt early disease and to prevent progression and vision loss.
Atmospheric new-particle formation affects climate and is one of the least understood atmospheric aerosol processes. The complexity and variability of the atmosphere has hindered elucidation of the fundamental mechanism of new-particle formation from gaseous precursors. We show, in experiments performed with the CLOUD (Cosmics Leaving Outdoor Droplets) chamber at CERN, that sulfuric acid and oxidized organic vapors at atmospheric concentrations reproduce particle nucleation rates observed in the lower atmosphere. The experiments reveal a nucleation mechanism involving the formation of clusters containing sulfuric acid and oxidized organic molecules from the very first step. Inclusion of this mechanism in a global aerosol model yields a photochemically and biologically driven seasonal cycle of particle concentrations in the continental boundary layer, in good agreement with observations.
Modern humans arrived in Europe similar to 45,000 years ago, but little is known about their genetic composition before the start of farming similar to 8,500 years ago. Here we analyse genome-wide data from 51 Eurasians from similar to 45,000-7,000 years ago. Over this time, the proportion of Neanderthal DNA decreased from 3-6% to around 2%, consistent with natural selection against Neanderthal variants in modern humans. Whereas there is no evidence of the earliest modern humans in Europe contributing to the genetic composition of present-day Europeans, all individuals between similar to 37,000 and similar to 14,000 years ago descended from a single founder population which forms part of the ancestry of present-day Europeans. An similar to 35,000-year-old individual from northwest Europe represents an early branch of this founder population which was then displaced across a broad region, before reappearing in southwest Europe at the height of the last Ice Age similar to 19,000 years ago. During the major warming period after similar to 14,000 years ago, a genetic component related to present-day Near Easterners became widespread in Europe. These results document how population turnover and migration have been recurring themes of European prehistory.