8 research outputs found
Geographic variation of mutagenic exposures in kidney cancer genomes
International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics
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Centrifuge modelling of hollow heated piles in saturated sand
Thermal piles are a sustainable foundation solution which support structural load whilst generating geothermal energy. Current design practice has been developed for conventional solid concrete thermal piles. This paper focusses on the use of a new innovative hollow thermal pile, the HIPER pile, developed in collaboration with Keltbray Piling. This pile is significantly more thermally efficient; leading to greater temperature gradients than could be expected with conventional thermal piles. A total of four centrifuge model tests at 50g in sand have been conducted to investigate the effects of heating and cooling cycles on pile behaviour under constant load. During testing the pile head movement, pile temperature, and soil temperature were recorded. Relationships between pile movement and thermal cycles are presented