Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM

Strategic planning for saving the lives of mothers, newborns and children and preventing stillbirths in KwaZulu-Natal province South Africa: modelling using the Lives Saved Tool (LiST)

BACKGROUND: KwaZulu-Natal province in South Africa has the largest population of children under the age of five and experiences the highest number of child births per annum in the country. Its population has also been ravaged by the dual epidemics of HIV and TB and it has struggled to meet targets for maternal and child mortality. In South Africa’s federal system, provinces have decision-making power on the prioritization and allocation of resources within their jurisdiction. As part of strategic planning for 2015–2019, KwaZulu-Natal provincial authorities requested an assessment of current mortality levels in the province and identification and costing of priority interventions for saving additional maternal, newborn and child lives, as well as preventing stillbirths in the province. METHODS: The Lives Saved Tool (LiST) was used to determine the set of interventions, which could save the most additional maternal and child lives and prevent stillbirths from 2015–2019, and the costs of these. The impact of family planning was assessed using two scenarios by increasing baseline coverage of modern contraception by 0.5 percentage points or 1 percentage point per annum. RESULTS: A total of 7,043 additional child and 297 additional maternal lives could be saved, and 2,000 stillbirths could be prevented over five years. Seventeen interventions account for 75 % of additional lives saved. Increasing family planning contributes to a further reduction of up to 137 maternal and 3,168 child deaths. The set of priority interventions scaled up to achievable levels, with no increase in contraception would require an additional US$91 million over five years or US$1.72 per capita population per year. By increasing contraceptive prevalence by one percentage point per year, overall costs to scale up to achievable coverage package, decrease by US$24 million over five years. CONCLUSION: Focused attention on a set of key interventions could have a significant impact on averting stillbirths and maternal and neonatal mortality in KwaZulu-Natal. Concerted effort to prioritize family planning will save more lives overall and has the potential to decrease costs in other areas of maternal and child care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-2661-x) contains supplementary material, which is available to authorized users

Emerging era of “somes”: polymersomes as versatile drug delivery carrier for cancer diagnostics and therapy

Over the past two decades, polymersomes have been widely investigated for the delivery of diagnostic and therapeutic agents in cancer therapy. Polymersomes are stable polymeric vesicles, which are prepared using amphiphilic block polymers of different molecular weights. The use of high molecular weight amphiphilic copolymers allows for possible manipulation of membrane characteristics, which in turn enhances the efficiency of drug delivery. Polymersomes are more stable in comparison with liposomes and show less toxicity in vivo. Furthermore, their ability to encapsulate both hydrophilic and hydrophobic drugs, significant biocompatibility, robustness, high colloidal stability, and simple methods for ligands conjugation make polymersomes a promising candidate for therapeutic drug delivery in cancer therapy. This review is focused on current development in the application of polymersomes for cancer therapy and diagnosis. Graphical abstract