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BackgroundRecent assessments show continued decline in child mortality in Papua New Guinea (PNG), yet complete subnational analyses remain rare. This study aims to estimate under-five mortality in PNG at national and subnational levels to examine the importance of geographical inequities in health outcomes and track progress towards Millennium Development Goal (MDG) 4.MethodologyWe performed retrospective data validation of the Demographic and Health Survey (DHS) 2006 using 2000 Census data, then applied advanced indirect methods to estimate under-five mortality rates between 1976 and 2000.FindingsThe DHS 2006 was found to be unreliable. Hence we used the 2000 Census to estimate under-five mortality rates at national and subnational levels. During the period under study, PNG experienced a slow reduction in national under-five mortality from approximately 103 to 78 deaths per 1,000 live births. Subnational analyses revealed significant disparities between rural and urban populations as well as inter- and intra-regional variations. Some of the provinces that performed the best (worst) in terms of under-five mortality included the districts that performed worst (best), with district-level under-five mortality rates correlating strongly with poverty levels and access to services.ConclusionsThe evidence from PNG demonstrates substantial within-province heterogeneity, suggesting that under-five mortality needs to be addressed at subnational levels. This is especially relevant in countries, like PNG, where responsibility for health services is devolved to provinces and districts. This study presents the first comprehensive estimates of under-five mortality at the district level for PNG. The results demonstrate that for countries that rely on few data sources even greater importance must be given to the quality of future population surveys and to the exploration of alternative options of birth and death surveillance.

Standard transgenic cell line generation requires screening 100-1000s of colonies to isolate correctly edited cells. We describe CRISPRa On-Target Editing Retrieval (CRaTER) which enriches for cells with on-target knock-in of a cDNA-fluorescent reporter transgene by transient activation of the targeted locus followed by flow sorting to recover edited cells. We show CRaTER recovers rare cells with heterozygous, biallelic-editing of the transcriptionally-inactive MYH7 locus in human induced pluripotent stem cells (hiPSCs), enriching on average 25-fold compared to standard antibiotic selection. We leveraged CRaTER to enrich for heterozygous knock-in of a library of single nucleotide variants (SNVs) in MYH7, a gene in which missense mutations cause cardiomyopathies, and recovered hiPSCs with 113 different MYH7 SNVs. We differentiated these hiPSCs to cardiomyocytes and show MYH7 fusion proteins can localize as expected. Thus, CRaTER substantially reduces screening required for isolation of gene-edited cells, enabling generation of transgenic cell lines at unprecedented scale.

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