Ambient air quality and human health in India

700 million Indians have used solid fuels in their homes for the last 30 years, contributing substantially to air pollutant emissions. The Indian economy and industrial, power generation, and transport sectors have grown considerably over the last decade, increasing emissions of air pollutants. These air pollutant emissions have caused present-day concentrations of ambient PM2.5 and O3 in India to be amongst the highest in the world. Exposure to this air pollution is the second leading risk factor in India, contributing one-quarter of the global disease burden attributable to air pollution exposure. Air pollutant emissions are predicted to grow extensively over the coming years in India. Despite the importance of air quality in India, it remains relatively understudied, and knowledge of the sources and processes causing air pollution is limited. This thesis aims to understand the contribution of different pollution sources to the attributable disease burden from ambient air pollution exposure in India and the effects of future air pollution control pathways. The attributable disease burden from ambient PM2.5 exposure in India is substantial, where large reductions in emissions will be required to reduce the health burden due to the non-linear exposure-response relationship. The attributable disease burden from ambient O3 exposure is larger than previously thought and is of similar magnitude to that from PM2.5 in the future. Key sources contributing to the present day disease burden from ambient PM2.5 and O3 exposure are the emissions from the residential combustion of solid fuels, land transport, and coal combustion in power plants. The attributable disease burden is estimated to increase in the future due to population ageing and growth. Stringent air pollution control pathways are required to provide critical public health benefits in India in a challenging environment. A key focus should be to reduce the combustion of solid fuels

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches