METHODS: We developed a decision analytic model to estimate the lifetime costs and quality-adjusted life-years (QALYs) accrued through BRCA mutation testing or routine clinical surveillance (RCS) for a hypothetical cohort of 1000 early-stage breast cancer patients aged 40 years. In the model, patients would decide whether to accept testing and to undertake risk-reducing mastectomy, oophorectomy, tamoxifen, combinations or neither. We calculated the incremental cost-effectiveness ratio (ICER) from the health system perspective. A series of sensitivity analyses were performed.

RESULTS: In the base case, testing generated 11.2 QALYs over the lifetime and cost US$4815 per patient whereas RCS generated 11.1 QALYs and cost US$4574 per patient. The ICER of US$2725/QALY was below the cost-effective thresholds. The ICER was sensitive to the discounting of cost, cost of BRCA mutation testing and utility of being risk-free, but the ICERs remained below the thresholds. Probabilistic sensitivity analysis showed that at a threshold of US$9500/QALY, 99.9% of simulations favoured BRCA mutation testing over RCS.

RESULTS: In this study, phylogeography of a mangrove tree Sonneratia alba was studied by sequencing three chloroplast fragments and seven nuclear genes. A low level of genetic diversity at the population level was detected across its range, especially at the range margins, which was mainly attributed to the steep sea-level drop and associated climate fluctuations during the Pleistocene glacial periods. Extremely small effective population size (Ne) was inferred in populations from both eastern and western Malay Peninsula (44 and 396, respectively), mirroring the fragility of mangrove plants and their paucity of robustness against future climate perturbations and human activity. Two major genetic lineages of high divergence were identified in the two mangrove biodiversity centres: the Indo-Malesia and Australasia regions. The estimated splitting time between these two lineages was 3.153 million year ago (MYA), suggesting a role for pre-Pleistocene events in shaping the major diversity patterns of mangrove species. Within the Indo-Malesia region, a subdivision was implicated between the South China Sea (SCS) and the remaining area with a divergence time of 1.874 MYA, corresponding to glacial vicariance when the emerged Sunda Shelf halted genetic exchange between the western and eastern coasts of the Malay Peninsula during Pleistocene sea-level drops. Notably, genetic admixture was observed in populations at the boundary regions, especially in the two populations near the Malacca Strait, indicating secondary contact between divergent lineages during interglacial periods. These interregional genetic exchanges provided ample opportunity for the re-use of standing genetic variation, which could facilitate mangrove establishment and adaptation in new habitats, especially in the context of global climate changes.