International comparisons of neurodevelopmental outcomes in infants born very preterm

We summarise rates of survival and neurodevelopmental impairment in very (<32 weeks' gestation) and extremely (<28 weeks' gestation) preterm infants using data from recent meta-analyses. Methodological issues that require consideration when comparing international data are highlighted using examples of population-based or multi-centre cohorts of children born extremely preterm. The impact of baseline population, outcome definition, gestational age assessment, age at neurodevelopmental assessment, year of birth and follow-up rates are discussed. The impact of the intensity of perinatal care and of post-discharge management on survival and neurodevelopmental outcomes is also discussed. There is a future need for harmonisation of data collection and for more accurate and standardised reporting of neurodevelopmental outcomes in very preterm children

Care of extremely premature babies in England, 1995 – Present

This thesis, arising from the EPICure studies into extremely preterm births, seeks to explain demographic, clinical and organisational factors associated with a large increase in admissions to neonatal intensive care. Using six pre-existing data sets, long with a repeat Unit Profile Study of English perinatal centres conducted in 2011 as part of this thesis, three studies were performed: • Validation of the 44% increase in the number of admissions to neonatal intensive care at 22–25 weeks gestation seen between 1995 and 2006 in England was attempted using three methods of probabilistic record linkage with Hospital Episode Statistics (HES) data. • The effects of antenatal steroid administration, tocolysis and Caesarean delivery on perinatal outcomes in the extremely preterm population were investigated. • Changes in organisational characteristics – staffing and “activity” (expressed as throughput and intensity) – that have occurred in England were examined using data from three time points. An increase was seen in the number of extremely premature babies in HES data. Linkage with EPICure data demonstrated that routine data are insufficiently precise for use in epidemiological investigations at the margins of viability. Tocolysis was associated with improved outcomes. Antenatal steroids were associated with improved outcomes at birth following vaginal delivery. No effect was demonstrated for Caesarean delivery on birth outcomes but there was evidence of case selection at gestations below 26 weeks. Organisational data (from 1997, 2006 and 2011) demonstrated reduced numbers of cots between 1997 and 2011 with increases in both throughput and intensity of workload. Staffing levels increased, but still failed to meet recommended standards. Current knowledge of extremely low gestational age births is inadequate for national policy or health care reorganisation. Suggestions were made for how knowledge could be improved

Maternal and infant morbidity following birth before 27 weeks of gestation: a single centre study

Delivery at extreme preterm gestational ages (GA) [Formula: see text] weeks is challenging with limited evidence often focused only on neonatal outcomes. We reviewed management and short term maternal, fetal and neonatal outcomes of births for 132 women (22 + 0 to 26 + 6 weeks' GA) with a live fetus at admission to hospital and in labour or at planned emergency Caesarean section: 103 singleton and 29 (53 live fetuses) twin gestations. Thirty women (23%) had pre-existing medical problems, 110 (83%) had antenatal complications; only 17 (13%) women experienced neither. Major maternal labour and delivery complications affected 35 women (27%). 151 fetuses (97%) were exposed to antenatal steroids, 24 (15%) to tocolysis and 70 (45%) to magnesium sulphate. Delivery complications affected 11 fetuses, with 12 labour or delivery room deaths; survival to discharge was 75% (117/156), increasing with GA: 25% (1/4), 75% (18/24), 69% (29/42), 73% (33/45) and 88% (36/41) at 22, 23, 24, 25 and 26 weeks GA respectively (p = 0.024). No statistically important impact was seen from twin status, maternal illness or obstetric management. Even in a specialist perinatal unit antenatal and postnatal maternal complications are common in extreme preterm births, emphasising the need to include maternal as well as neonatal outcomes

Accounting for Underreporting in Mathematical Modeling of Transmission and Control of COVID-19 in Iran

Iran has been the country most affected by the outbreak of SARS-CoV-2 in the Middle East. With a relatively high case fatality ratio and limited testing capacity, the number of confirmed cases reported is suspected to suffer from significant underreporting. Therefore, understanding the transmission dynamics of COVID-19 and assessing the effectiveness of the interventions that have taken place in Iran while accounting for the uncertain level of underreporting is of critical importance. In this paper, we developed a compartmental transmission model to estimate the time-dependent effective reproduction number since the beginning of the outbreak in Iran. We associate the variations in the effective reproduction number with a timeline of interventions and national events. The estimation method accounts for the underreporting due to low case ascertainment. Our estimates of the effective reproduction number ranged from 0.66 to 1.73 between February and April 2020, with a median of 1.16. We estimate a reduction in the effective reproduction number during this period, from 1.73 (95% CI 1.60–1.87) on 1 March 2020 to 0.69 (95% CI 0.68–0.70) on 15 April 2020, due to various non-pharmaceutical interventions. The series of non-pharmaceutical interventions and the public compliance that took place in Iran are found to be effective in slowing down the speed of the spread of COVID-19. However, we argue that if the impact of underreporting is overlooked, the estimated transmission and control dynamics could mislead public health decisions, policy makers, and the general public

Accounting for Underreporting in Mathematical Modeling of Transmission and Control of COVID-19 in Iran

Iran has been the country most affected by the outbreak of SARS-CoV-2 in the Middle East. With a relatively high case fatality ratio and limited testing capacity, the number of confirmed cases reported is suspected to suffer from significant underreporting. Therefore, understanding the transmission dynamics of COVID-19 and assessing the effectiveness of the interventions that have taken place in Iran while accounting for the uncertain level of underreporting is of critical importance. In this paper, we developed a compartmental transmission model to estimate the time-dependent effective reproduction number since the beginning of the outbreak in Iran. We associate the variations in the effective reproduction number with a timeline of interventions and national events. The estimation method accounts for the underreporting due to low case ascertainment. Our estimates of the effective reproduction number ranged from 0.66 to 1.73 between February and April 2020, with a median of 1.16. We estimate a reduction in the effective reproduction number during this period, from 1.73 (95% CI 1.60–1.87) on 1 March 2020 to 0.69 (95% CI 0.68–0.70) on 15 April 2020, due to various non-pharmaceutical interventions. The series of non-pharmaceutical interventions and the public compliance that took place in Iran are found to be effective in slowing down the speed of the spread of COVID-19. However, we argue that if the impact of underreporting is overlooked, the estimated transmission and control dynamics could mislead public health decisions, policy makers, and the general public

The two-hour orbit of a binary millisecond X-ray pulsar

Typical radio pulsars are magnetized neutron stars that are born rapidly rotating and slow down as they age on time scales of 10 to 100 million years. However, millisecond radio pulsars spin very rapidly even though many are billions of years old. The most compelling explanation is that they have been "spun up" by the transfer of angular momentum during accretion of material from a companion star in so-called low-mass X-ray binary systems, LMXBs. (LMXBs consist of a neutron star or black hole accreting from a companion less than one solar mass.) The recent detection of coherent X-ray pulsations with a millisecond period from a suspected LMXB system appears to confirm this link. Here we report observations showing that the orbital period of this binary system is two hours, which establishes it as an LMXB. We also find an apparent modulation of the X-ray flux at the orbital period (at the two per cent level), with a broad minimum when the pulsar is behind this low-mass companion star. This system seems closely related to the "black widow" millisecond radio pulsars, which are evaporating their companions through irradiation. It may appear as an eclipsing radio pulsar during periods of X-ray quiescence.Comment: 4 pages with 1 figure. Style files included. Fig. 2 deleted and text revised. To appear in Nature. Press embargo until 18:00 GMT on 1998 July 2

Grid-texture mechanisms in human vision:contrast detection of regular sparse micro-patterns requires specialist templates

Previous work has shown that human vision performs spatial integration of luminance contrast energy, where signals are squared and summed (with internal noise) over area at detection threshold. We tested that model here in an experiment using arrays of micro-pattern textures that varied in overall stimulus area and sparseness of their target elements, where the contrast of each element was normalised for sensitivity across the visual field. We found a power-law improvement in performance with stimulus area, and a decrease in sensitivity with sparseness. While the contrast integrator model performed well when target elements constituted 50–100% of the target area (replicating previous results), observers outperformed the model when texture elements were sparser than this. This result required the inclusion of further templates in our model, selective for grids of various regular texture densities. By assuming a MAX operation across these noisy mechanisms the model also accounted for the increase in the slope of the psychometric function that occurred as texture density decreased. Thus, for the first time, mechanisms that are selective for texture density have been revealed at contrast detection threshold. We suggest that these mechanisms have a role to play in the perception of visual textures

Variations in patterns of care across neonatal units and their associations with outcomes in very preterm infants: the French EPIPAGE-2 cohort study

OBJECTIVES: To describe patterns of care for very preterm (VP) babies across neonatal intensive care units (NICUs) and associations with outcomes. DESIGN: Prospective cohort study, EPIPAGE-2. SETTING: France, 2011. PARTICIPANTS: 53 (NICUs); 2135 VP neonates born at 27 to 31 weeks. OUTCOME MEASURES: Clusters of units, defined by the association of practices in five neonatal care domains - respiratory, cardiovascular, nutrition, pain management and neurodevelopmental care. Mortality at 2 years corrected age (CA) or severe/moderate neuro-motor or sensory disabilities and proportion of children with scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ). METHODS: Hierarchical cluster analysis to identify clusters of units. Comparison of outcomes between clusters, after adjustment for potential cofounders. RESULTS: Three clusters were identified: Cluster 1 with higher proportions of neonates free of mechanical ventilation at 24 hours of life, receiving early enteral feeding, and neurodevelopmental care practices (26 units; n=1118 babies); Cluster 2 with higher levels of patent ductus arteriosus and pain screening (11 units; n=398 babies); Cluster 3 with higher use of respiratory, cardiovascular and pain treatments (16 units; n=619 babies). No difference was observed between clusters for the baseline maternal and babies' characteristics. No differences in outcomes were observed between Clusters 1 and 3. Compared with Cluster 1, mortality at 2 years CA or severe/moderate neuro-motor or sensory disabilities was lower in Cluster 2 (adjusted OR 0.46, 95% CI 0.25 to 0.84) but with higher proportion of children with an ASQ below threshold (adjusted OR 1.49, 95% CI 1.07 to 2.08). CONCLUSION: In French NICUs, care practices for VP babies were non-randomly associated. Differences between clusters were poorly explained by unit or population differences, but were associated with mortality and development at 2 years. Better understanding these variations may help to improve outcomes for VPT babies, as it is likely that some of these discrepancies are unwarranted