Lung adenocarcinoma promotion by air pollutants

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden

A general model for the marketing of seasonal products

We discuss a general model for the marketing of seasonal products, namely products for which the time intervals devoted to production and sales are distinct. The firm can advertise the product, thus affecting the sales in two different ways, namely directly (customer effect) and indirectly (retailers effect). A two-dimensional goodwill variable represents the (retailes, customers)-advertising capital stock. The dynamics of the system in the sales interval only is analysed, in order to determine the levels of goodwill and inventory at the beginning of such time intervla and subsequent advertising policy, so as to maximize the discounted net profit

Random PERT: application to physical activity/sports programs

Random PERT, Physical Activity, Sport Programs,