Changing consumption of resources for respiratory support and short-term outcomes in four consecutive geographical cohorts of infants born extremely preterm over 25 years since the early 1990s

OBJECTIVES:It is unclear how newer methods of respiratory support for infants born extremely preterm (EP; 22-27 weeks gestation) have affected in-hospital sequelae. We aimed to determine changes in respiratory support, survival and morbidity in EP infants since the early 1990s. DESIGN:Prospective longitudinal cohort study. SETTING:The State of Victoria, Australia. PARTICIPANTS:All EP births offered intensive care in four discrete eras (1991-1992 (24 months): n=332, 1997 (12 months): n=190, 2005 (12 months): n=229, and April 2016-March 2017 (12 months): n=250). OUTCOME MEASURES:Consumption of respiratory support, survival and morbidity to discharge home. Cost-effectiveness ratios describing the average additional days of respiratory support associated per additional survivor were calculated. RESULTS:Median duration of any respiratory support increased from 22 days (1991-1992) to 66 days (2016-2017). The increase occurred in non-invasive respiratory support (2 days (1991-1992) to 51 days (2016-2017)), with high-flow nasal cannulae, unavailable in earlier cohorts, comprising almost one-half of the duration in 2016-2017. Survival to discharge home increased (68% (1991-1992) to 87% (2016-2017)). Cystic periventricular leukomalacia decreased (6.3% (1991-1992) to 1.2% (2016-2017)), whereas retinopathy of prematurity requiring treatment increased (4.0% (1991-1992) to 10.0% (2016-2017)). The average additional costs associated with one additional infant surviving in 2016-2017 were 200 (95% CI 150 to 297) days, 326 (183 to 1127) days and 130 (70 to 267) days compared with 1991-1992, 1997 and 2005, respectively. CONCLUSIONS:Consumption of resources for respiratory support has escalated with improved survival over time. Cystic periventricular leukomalacia reduced in incidence but retinopathy of prematurity requiring treatment increased. How these changes translate into long-term respiratory or neurological function remains to be determined.Jeanie L Y Cheong, Joy E Olsen, Li Huang, Kim M Dalziel, Rosemarie A Boland, Alice C Burnett ... et al

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Repeat antenatal betamethasone and cardiometabolic outcomes

BACKGROUND: Repeat dose(s) of antenatal betamethasone are recommended for women at <32 weeks with ongoing risk of preterm birth. However, there is concern that use of repeat dose(s) in fetal growth restriction (FGR) may increase the risk of later cardiometabolic disease. METHODS: We undertook secondary analysis of data from the Australasian Collaborative Trial of Repeat Doses of Corticosteroids Midchildhood Outcome Study to determine if FGR influences the effect of repeat betamethasone on growth and cardiometabolic function. At 6 to 8 years, children underwent anthropometry, dual energy x-ray absorptiometry, intravenous glucose tolerance testing, ambulatory blood pressure monitoring, and spirometry. FGR was defined as severe FGR at entry, cesarean delivery for FGR, or customized birth weight below the third centile. RESULTS: Of 266 children assessed, FGR occurred in 43 of 127 (34%) exposed to repeat betamethasone and 44 of 139 (32%) exposed to placebo. There was an interaction between FGR and repeat betamethasone treatment for the effect on height (z score mean difference [95% confidence interval]; FGR: 0.59 [0.01 to 1.17]; non-FGR: −0.29 [−0.69 to 0.10]; P = .01). However, FGR did not influence the effect of repeat betamethasone on cardiometabolic function, which was similar in treatment groups, both in FGR and non-FGR subgroups. CONCLUSIONS: Repeat antenatal betamethasone treatment had no adverse effects on cardiometabolic function, even in the presence of FGR. It may have a positive effect on height in FGR. Clinicians should use repeat doses of antenatal corticosteroids when indicated before preterm birth, regardless of FGR, in view of the associated neonatal benefits.Robert D. Cartwright, Jane E. Harding, Caroline A. Crowther, Wayne S. Cutfield, Malcolm R. Battin, Stuart R. Dalziel, Christopher J.D. McKinlay, on behalf of the ACTORDS Follow-up Grou