General anaesthetic and airway management practice for obstetric surgery in England: a prospective, multi-centre observational study

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients' (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16-22) and failed intubation in 1 in 312 (95%CI 1 in 169-667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%)

Quantitative and comprehensive analysis of Ciona notochord organogenesis

Doctor of PhilosophyDepartment of BiologyMichael VeemanTechnical advances in imaging and genomics are making developmental biology increasingly quantitative. The invertebrate chordate Ciona has small embryos, a compact genome, and a simple, yet stereotypically chordate body plan, making it well suited to quantitative, systems-level studies of organogenesis. This is particularly true for the Ciona notochord, which is comprised of only 40 cells that form a simple tapered rod. The unifying theme of this dissertation is to comprehensively and quantitatively analyze the development of the Ciona notochord in terms of both the cell behaviors driving morphogenesis and the gene regulatory networks controlling notochord cell fate. Ciona embryos develop rapidly, and, since they are poikilotherms, at a rate proportional to the temperature at which they are incubated. I required precise embryonic staging of the temporally dynamic transcriptional and morphogenetic processes I was studying in order to make accurate conclusions. To facilitate this, we developed a simple yet powerful open source device, the Temperature Adjusted Developmental Timer, which allows researchers to stage embryos accurately with respect to temperature in real time and requires only the estimation of two simple species-specific parameters. Using quantitative confocal microscopy and computational image analysis, I quantified how a series of subtle but iterative asymmetric divisions give rise to the observed cell volume differences along the AP axis of the post-mitotic notochord which contributes to its tapered shape. I partitioned the contributions of three cellular mechanisms to the observed asymmetric divisions using a modeling framework and uncovered a previously unappreciated role of mother-cell shape in this process. To characterize the earliest gene-regulatory network (GRN) of the notochord, I collected a single-cell RNA-sequencing (scRNAseq) timecourse of early Ciona development during the stages in which notochord and many other distinct cell fates are established. This was performed both with and without a pharmacological inhibitor of a MAPK-dependent signal involved in many early cell fate decisions including notochord. The scRNAseq data revealed that the earliest signatures of the Ciona notochord GRN involve transcriptional activation by Ets and Zic family transcription factors in parallel to, and not downstream of the notochord specific transcription factor Brachyury. These diverse studies of notochord organogenesis are linked in being deeply quantitative and based on assessing cellular properties and behaviors with single-cell resolution on a scale ranging from an entire organ primordium to an entire embryo. Both the asymmetric division study and the scRNAseq study have broad implications beyond the Ciona notochord and contribute to a modern understanding of the processes of development at the single-cell level