Timing and documentation of key events in neonatal resuscitation

Only a minority of babies require extended resuscitation at birth. Resuscitations concerning babies who die or who survive with adverse outcomes are increasingly subject to medicolegal scrutiny. Our aim was to describe real-life timings of key resuscitation events observed in a historical series of newborns who required full resuscitation at birth. Twenty-seven babies born in our centre over a 10-year period had an Apgar score of 0 at 1 min and required full resuscitation. The median (95% confidence interval) postnatal age at achieving key events were commencing cardiac compressions, 2.0 (1.5–4.0) min; endotracheal intubation, 3.8 (2.0–6.0) min; umbilical venous catheterisation 9.0 (7.5–12.0) min; and administration of first adrenaline dose 10.0 (8.0–14.0) min. Conclusion: The wide range of timings presented from real-life cases may prove useful to clinicians involved in medical negligence claims and provide a baseline for quality improvements in resuscitation training

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Laurentian Great Lakes Phytoplankton and Their Water Quality Characteristics, Including a Diatom-Based Model for Paleoreconstruction of Phosphorus

Recent shifts in water quality and food web characteristics driven by anthropogenic impacts on the Laurentian Great Lakes warranted an examination of pelagic primary producers as tracers of environmental change. The distributions of the 263 common phytoplankton taxa were related to water quality variables to determine taxon-specific responses that may be useful in indicator models. A detailed checklist of taxa and their environmental optima are provided. Multivariate analyses indicated a strong relationship between total phosphorus (TP) and patterns in the diatom assemblages across the Great Lakes. Of the 118 common diatom taxa, 90 (76%) had a directional response along the TP gradient. We further evaluated a diatom-based transfer function for TP based on the weighted-average abundance of taxa, assuming unimodal distributions along the TP gradient. The r2 between observed and inferred TP in the training dataset was 0.79. Substantial spatial and environmental autocorrelation within the training set of samples justified the need for further model validation. A randomization procedure indicated that the actual transfer function consistently performed better than functions based on reshuffled environmental data. Further, TP was minimally confounded by other environmental variables, as indicated by the relatively large amount of unique variance in the diatoms explained by TP. We demonstrated the effectiveness of the transfer function by hindcasting TP concentrations using fossil diatom assemblages in a Lake Superior sediment core. Passive, multivariate analysis of the fossil samples against the training set indicated that phosphorus was a strong determinant of historical diatom assemblages, verifying that the transfer function was suited to reconstruct past TP in Lake Superior. Collectively, these results showed that phytoplankton coefficients for water quality can be robust indicators of Great Lakes pelagic condition. The diatom-based transfer function can be used in lake management when retrospective data are needed for tracking long-term degradation, remediation and trajectories