Although delivery is widely used for preterm babies failing to thrive in utero, the effect of altering delivery timing has never been assessed in a randomised controlled trial. We aimed to compare ...the effect of delivering early with delaying birth for as long as possible.
548 pregnant women were recruited by 69 hospitals in 13 European countries. Participants had fetal compromise between 24 and 36 weeks, an umbilical-artery doppler waveform recorded, and clinical uncertainty about whether immediate delivery was indicated. Before birth, 588 babies were randomly assigned to immediate delivery (n=296) or delayed delivery until the obstetrician was no longer uncertain (n=292). The main outcome was death or disability at or beyond 2 years of age. Disability was defined as a Griffiths developmental quotient of 70 or less or the presence of motor or perceptual severe disability. Analysis was by intention-to-treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN41358726.
Primary outcomes were available on 290 (98%) immediate and 283 (97%) deferred deliveries. Overall rate of death or severe disability at 2 years was 55 (19%) of 290 immediate births, and 44 (16%) of 283 delayed births. With adjustment for gestational age and umbilical-artery doppler category, the odds ratio (95% CrI) was 1·1 (0·7–1·8). Most of the observed difference was in disability in babies younger than 31 weeks of gestation at randomisation: 14 (13%) immediate versus five (5%) delayed deliveries. No important differences in the median Griffiths developmental quotient in survivors was seen.
The lack of difference in mortality suggests that obstetricians are delivering sick preterm babies at about the correct moment to minimise mortality. However, they could be delivering too early to minimise brain damage. These results do not lend support to the idea that obstetricians can deliver before terminal hypoxaemia to improve brain development.
Ultrafast dispersed pump-dump-probe spectroscopy was applied to HBDI (4‘-hydroxybenzylidene-2,3-dimethyl-imidazolinone), a model green fluorescent protein (GFP) chromophore in solution with different ...protonation states. The measured three-dimensional data was analyzed using a global analysis method that enables the spectral and temporal characterization of overlapping photoinduced transient states. A unified phenomenological model is presented to describe the observed data. Two excitation pathways are identified: a 1-photon excited-state twisting and a 2-photon ionization process. The ionization pathway results in the generation of solvated electrons and HBDI radicals. The twisting dynamics was resolved on both electronic states with slower twisting on the ground state than the excited state. This is ascribed to the multidimensional hula-twist mechanism. A weak viscosity dependence was observed when the aqueous solution data were contrasted with the signals collected in a 66% glycerol/water solution.
Analysis of parent and teacher Developmental Behavior Checklist (DBC) ratings on a combined sample of 1,536 Dutch and Australian children (ages 3-22) with mild to profound intellectual disabilities ...produced five subscales: Disruptive/Antisocial, Self-Absorbed, Communication Disturbance, Anxiety, and Social Relating. Internal consistency of the subscales ranged from .66 to .91. (Contains references.) (Author/CR)
Objectives To compare the effect of delivering early to pre‐empt terminal hypoxaemia with delaying for as long as possible to increase maturity.
Design A randomised controlled trial.
Setting 69 ...hospitals in 13 European countries.
Participants Pregnant women with fetal compromise between 24 and 36 weeks, an umbilical artery Doppler waveform recorded and clinical uncertainty whether immediate delivery was indicated.
Methods The interventions were ‘immediate delivery’ or ‘delay until the obstetrician is no longer uncertain’. The data monitoring and analysis were Bayesian.
Main outcome measures ‘Survival to hospital discharge’ and ‘developmental quotient at two years of age’, this latter to be reported later.
Results Of 548 women (588 babies) recruited, outcomes were available on 547 mothers (587 babies). The median time‐to‐delivery intervals were 0.9 days in the immediate group and 4.9 days in the delay group. Total deaths prior to discharge were 29 (10%) in the immediate group versus 27 (9%) in the delay group (odds ratio 1.1, 95% CI 0.61–1.8). Total caesarean sections were 249 (91%) in the immediate group versus 217 (79%) in the delay group: (OR 2.7; 95% CI 1.6–4.5). These odds ratios were similar for those randomised at gestational ages above or below 30 weeks.
Interpretation The lack of difference in overall mortality suggests that clinicians participating in this trial were on average prepared to randomise at about the correct equivocal threshold between delivery and delay. However, there was insufficient evidence to convince enthusiasts for either immediate or delayed delivery that they were wrong.
To compare the effect of delivering early to pre-empt terminal hypoxaemia with delaying for as long as possible to increase maturity.
A randomised controlled trial.
69 hospitals in 13 European ...countries.
Pregnant women with fetal compromise between 24 and 36 weeks, an umbilical artery Doppler waveform recorded and clinical uncertainty whether immediate delivery was indicated.
The interventions were ‘immediate delivery’ or ‘delay until the obstetrician is no longer uncertain’. The data monitoring and analysis were Bayesian.
‘Survival to hospital discharge’ and ‘developmental quotient at two years of age’, this latter to be reported later.
Of 548 women (588 babies) recruited, outcomes were available on 547 mothers (587 babies). The median time-to-delivery intervals were 0.9 days in the immediate group and 4.9 days in the delay group. Total deaths prior to discharge were 29 (10%) in the immediate group
versus 27 (9%) in the delay group (odds ratio 1.1, 95% CI 0.61–1.8). Total caesarean sections were 249 (91%) in the immediate group
versus 217 (79%) in the delay group: (OR 2.7; 95% CI 1.6–4.5). These odds ratios were similar for those randomised at gestational ages above or below 30 weeks.
The lack of difference in overall mortality suggests that clinicians participating in this trial were on average prepared to randomise at about the correct equivocal threshold between delivery and delay. However, there was insufficient evidence to convince enthusiasts for either immediate or delayed delivery that they were wrong.
A mechanical sector and linear array real-time scanner combined with a pulsed Doppler system was used for recording the flow velocity waveform in the internal carotid artery, the lower thoracic part ...of the descending aorta and umbilical artery in the human fetus. A total of 42 fetuses in normal pregnancy and nine growth-retarded fetuses between 26 and 41 weeks gestation was studied. In normal pregnancy the mean pulsatility index (PI) in the internal carotid artery varied between 1.5 and 1.6, in the descending aorta between 1.7 and 1.8 and in the umbilical artery between 0.7 and 1.3. In the growth-retarded fetuses the PI was reduced in the internal carotid artery and raised in the descending aorta and umbilical artery, suggesting an increased peripheral vascular resistance in the fetal body and placenta and a compensatory reduction in peripheral vascular resistance in the fetal cerebrum, i.e. a brain-sparing effect in the presence of fetal hypoxia.
Blue Light Using Flavin (BLUF) domains are increasingly being adopted for use in optogenetic constructs. Despite this, much remains to be resolved on the mechanism of their activation. The advent of ...unnatural amino acid mutagenesis opens up a new toolbox for the study of protein structural dynamics. The tryptophan analogue, 7-aza-Trp (7AW) was incorporated in the BLUF domain of the Activation of Photopigment and pucA (AppA) photoreceptor in order to investigate the functional dynamics of the crucial W104 residue during photoactivation of the protein. The 7-aza modification to Trp makes selective excitation possible using 310 nm excitation and 380 nm emission, separating the signals of interest from other Trp and Tyr residues. We used Förster energy transfer (FRET) between 7AW and the flavin to estimate the distance between Trp and flavin in both the light- and dark-adapted states in solution. Nanosecond fluorescence anisotropy decay and picosecond fluorescence lifetime measurements for the flavin revealed a rather dynamic picture for the tryptophan residue. In the dark-adapted state, the major population of W104 is pointing away from the flavin and can move freely, in contrast to previous results reported in the literature. Upon blue-light excitation, the dominant tryptophan population is reorganized, moves closer to the flavin occupying a rigidly bound state participating in the hydrogen-bond network around the flavin molecule.
Effects of plastic constraint on the fracture of materials have been studied extensively. Often in such studies, the plastic constraint is divided into in-plane and out-of-plane directions and each ...treated separately. Such a separation adds considerable complexity to the engineering structural integrity assessment analyses. Despite previous suggestions for unifying the effects of constraint in a single parameter, the current engineering assessments have not been updated due to lack of direct experimental validation of such parameters. In this study, we directly measured the effects of in-plane and out-of-plane constraints, for the first time, in the form of plastic zone around the crack using advanced experimental techniques. The measurement of constraints in four specimens with different levels of in and out of plane constraints, allowed us to show and relate the interdependency of in and out of plane constraints. The tests were carried out using synchrotron X-ray tomography with in-situ loading. Attenuation contrast between the constituents of the metal matrix composite material used allowed the tomograms to be analysed using digital volume correlation which calculated the full-field displacement within the samples. The displacement fields were used via a finite element framework to calculate the energy release rate in the form of the J-integral along the crack fronts. The measured plastic zone sizes, dependant on the combined level of in plane and out of plane constraints, were used successfully to rank the J-Integral at fracture of the samples. It was therefore proved the level of plastic constraint can be quantified by using the size of the plastic zone as without separating it into two components thus simplifying the treatment of constraint in structural analyses significantly.
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