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Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.

This study focuses on reconstructing the time-calibrated phylogeny of the nine families comprising the order Sapindales, representing a diverse and economically important group of eudicots including citrus, mahogany, tree-of-heaven, cashew, mango, pistachio, frankincense, myrrh, lychee, rambutan, maple, and buckeye. We sampled three molecular markers, plastid genes rbcL and atpB, and the trnL-trnLF spacer region, and covered one-third of the generic diversity of Sapindales. All three markers produced congruent phylogenies using maximum likelihood and Bayesian methods for a set of taxa that included outgroups, i.e., members of the closely related orders Brassicales and Malvales, and the more distantly related Crossosomatales, Ranunculales, and Ceratophyllales. All results confirmed the current delimitation of the families within Sapindales, and the monophyly of the order. Concerning inter-familial relationships, Biebersteiniaceae and Nitrariaceae formed a basal grade (or sister clade) to the rest of Sapindales with moderate support. The sister relationship of Kirkiaceae to Anacardiaceae and Burseraceae was strongly supported. The clade combining Anacardiaceae and Burseraceae as well as the clade combining Meliaceae, Simaroubaceae, and Rutaceae each received strong support. The sister relationship between Meliaceae and Simaroubaceae was moderately supported. The position of Sapindaceae could not be resolved with confidence. The Sapindales separated from their sister clade, comprising Brassicales and Malvales, in the Early Cretaceous at ca. 112 Ma, and diversified into the nine families from ca. 105 Ma until ca. 87 Ma during Early to Late Cretaceous times. Biebersteiniaceae and Nitrariaceae have the longest stem lineages observed in Sapindales, possibly indicating that extinction may have had a greater role in shaping their extant diversity than elsewhere within the order. Divergence within the larger families (Anacardiaceae, Burseraceae, Meliaceae, Rutaceae, Sapindaceae, Simaroubaceae) started during the Late Cretaceous, extending into the Paleogene and Neogene.

Background: Moderate therapeutic hypothermia (TH) initiated within 6 h of life reduces adverse neurodevelopmental outcomes in infants after perinatal hypoxic ischaemic insult. For infants born in non-tertiary centres, TH may be initiated manually en route to a neonatal intensive care unit (NICU). However, both over- and undercooling is reported with this strategy, precluding some infants from the benefits of TH. Objectives: To evaluate the impact of a region-wide educational programme on the safety and efficacy of manual cooling administered by the Wellington Neonatal Transport Service (NeTS). Methods: Clinical records of infants with hypoxic ischaemic encephalopathy (HIE) retrieved by the Wellington NeTS for TH between January 2012 and June 2017 were reviewed retrospectively. Temperature outcomes of infants retrieved before and after the education programme were compared. Results: A total of 101 infants were cooled manually by Wellington NeTS for TH during the study period. Education and training significantly reduced the rate of overcooling to ≤32.0°C (4/43 [9%] vs. 0/58, p = 0.02). However, there was no difference in the proportion of infants who achieved target rectal temperature within 6 h of life (29/43 [65%] vs. 35/58 [60%], p = 0.57). Conclusions: Introduction of a region-wide educational programme may have improved the safety of manual cooling during neonatal transport but it had a negligible impact on its efficacy. The use of servo-controlled cooling during transport should therefore be considered to improve access to the optimal neuroprotective benefits of TH for outborn infants with HIE.