Publications

Previous work has suggested that the drastic Khmer-Rouge-era changes to the family institution have not endured. Potentially more influential in the long term were the rapid socio-economic changes Cambodia underwent starting in the 1990s. We use four waves of the Cambodian Demographic and Health Surveys from 2000 to 2014 to document contemporary trends in marriage formation and dissolution. We find little change in the centrality of marriage, as both cohabitation and sex between unmarried partners remain quite rare. Marriage also continues to be nearly universal and early for women, but we find that the transition to self-arranged "love" marriages occurred earlier and faster than previously documented. A sign that parental endorsement may still matter though, marriage dissolution continues to be associated with spousal characteristics deemed undesirable by past generations. While higher among recent marriage cohorts, especially in the first year after marriage, levels of marriage dissolution remain comparatively low overall.

Spatial properties of tumour growth have profound implications for cancer progression, therapeutic resistance and metastasis. Yet, how spatial position governs tumour cell division remains difficult to evaluate in clinical tumours. Here, we demonstrate that faster division on the tumour periphery leaves characteristic genetic patterns, which become evident when a phylogenetic tree is reconstructed from spatially sampled cells. Namely, rapidly dividing peripheral lineages branch more extensively and acquire more mutations than slower-dividing centre lineages. We develop a Bayesian state-dependent evolutionary phylodynamic model (SDevo) that quantifies these patterns to infer the differential division rates between peripheral and central cells. We demonstrate that this approach accurately infers spatially varying birth rates of simulated tumours across a range of growth conditions and sampling strategies. We then show that SDevo outperforms state-of-the-art, non-cancer multi-state phylodynamic methods that ignore differential sequence evolution. Finally, we apply SDevo to single-time-point, multi-region sequencing data from clinical hepatocellular carcinomas and find evidence of a three- to six-times-higher division rate on the tumour edge. With the increasing availability of high-resolution, multi-region sequencing, we anticipate that SDevo will be useful in interrogating spatial growth restrictions and could be extended to model non-spatial factors that influence tumour progression.