33 research outputs found
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Assessing the impact of changes in surface cover, human behaviour and climate on energy partitioning across Greater London
Climate-sensitive urban design is an increasingly important consideration for city planners and policy makers.
This study demonstrates the use of a biophysical model to assess the response of urban climate to various
changes, including population growth, reduced energy use, urban development and urban greening initiatives.
Model inputs are intentionally derived using only publicly available information and assumptions involved in
collating the data are discussed. Results are summarised in terms of the energy partitioning which captures
changes in meteorology, surface characteristics and human behaviour. The model has been recently evaluated
for the region, and those findings are drawn upon here to discuss the model’s capabilities and limitations. Model
simulations demonstrate how both intentional and inadvertent changes to the urban landscape can alter the
urban climate. For example, the impact of population growth depends on where, and how, people are housed,
and recent changes in garden composition have reduced evaporation. This study has been designed so that model
output could be combined with socio-economic data in future, enabling both risk and vulnerability to be
considered together
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk