Pre-eclampsia screening in Denmark (PRESIDE): national validation study.

OBJECTIVES: To investigate the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for pre-eclampsia in a Danish population and compare screening performance with that of the current Danish strategy, which is based on maternal risk factors. METHODS: This was a prospective study of women with a singleton pregnancy attending for their first-trimester ultrasound scan and screening for aneuploidies at six Danish university hospitals between May 2019 and December 2020. Prenatal data on maternal characteristics and medical history were recorded, and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and serum placental growth factor (PlGF) were collected without performing a risk assessment for pre-eclampsia. Information on acetylsalicylic acid use was recorded. After delivery, pregnancy outcome, including gestational age at delivery and pre-eclampsia diagnosis, was recorded. Pre-eclampsia risk assessment for each woman was calculated blinded to outcome using the FMF screening algorithm following adjustment to the Danish population. Detection rates (DRs) of the FMF algorithm were calculated for a fixed screen-positive rate (SPR) of 10% and for the SPR achieved in the current Danish screening. RESULTS: A total of 8783 pregnant women were included, with a median age of 30.8 (interquartile range (IQR), 28.1-33.9) years. The majority were white (95%), naturally conceiving (90%), non-smokers (97%) and had no family history of pre-eclampsia (96%). The median body mass index was 23.4 (IQR, 21.2-26.6) kg/m2 . A complete risk assessment including maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A was available for 8156 women (92.9%). In these women, UtA-PI was measured bilaterally with a median value of 1.58 (IQR, 1.27-1.94) and the median resting MAP of 80.5 (IQR, 76.1-85.4) mmHg in two consecutive measurements. Among these, 303 (3.7%) developed pre-eclampsia, including 55 (0.7%) cases of pre-eclampsia with delivery < 37 weeks of gestation and 16 (0.2%) cases of pre-eclampsia with delivery < 34 weeks. At a SPR of 10%, combined screening using the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A had a DR of 77.4% (95% CI, 57.6-97.2%) for pre-eclampsia with delivery < 34 weeks, 66.8% (95% CI, 54.4-79.1%) for pre-eclampsia with delivery < 37 weeks and 44.1% (95% CI, 38.5-49.7%) for pre-eclampsia with delivery at any gestational age. The current Danish screening strategy using maternal risk factors detected 25.0% of women with pre-eclampsia with delivery < 34 weeks and 19.6% of women with pre-eclampsia with delivery < 37 weeks at a SPR of 3.4%. When applying the FMF algorithm including maternal characteristics, MAP, UtA-PI and PlGF at the fixed SPR of 3.4%, the DRs were 60.5% (95% CI, 36.9-84.1%) for PE with delivery < 34 weeks and 45.2% (95% CI, 32.0-58.5%) for PE with delivery < 37 weeks. CONCLUSION: In this large Danish multicenter study, the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A predicted 77.4% of cases with pre-eclampsia with delivery < 34 weeks and 66.8% of cases with pre-eclampsia with delivery < 37 weeks of gestation at a SPR of 10%, suggesting that the performance of the algorithm in a Danish cohort matches that in other populations. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The superstatistical nature and interoccurrence time of atmospheric mercury concentration fluctuations.

The probability density function (PDF) of the time intervals between subsequent extreme events in atmospheric Hg0 concentration data series from different latitudes has been investigated. The Hg0 dynamic possesses a long-term memory autocorrelation function. Above a fixed threshold Q in the data, the PDFs of the interoccurrence time of the Hg0 data are well described by a Tsallis q-Exponential function. This PDF behavior has been explained in the framework of superstatistics, where the competition between multiple mesoscopic processes affects the macroscopic dynamics. An extensive parameter µ, encompassing all possible fluctuations related to mesoscopic phenomena, has been identified. It follows a χ 2-distribution, indicative of the superstatistical nature of the overall process. Shuffling the data series destroys the long-term memory, the distributions become independent of Q, and the PDFs collapse on to the same exponential distribution. The possible central role of atmospheric turbulence on extreme events in the Hg0 data is highlighted.

Regions of open water and melting sea ice drive new particle formation in North East Greenland.

Atmospheric new particle formation (NPF) and growth significantly influences the indirect aerosol-cloud effect within the polar climate system. In this work, the aerosol population is categorised via cluster analysis of aerosol number size distributions (9-915 nm, 65 bins) taken at Villum Research Station, Station Nord (VRS) in North Greenland during a 7 year record (2010-2016). Data are clustered at daily averaged resolution; in total, we classified six categories, five of which clearly describe the ultrafine aerosol population, one of which is linked to nucleation events (up to 39% during summer). Air mass trajectory analyses tie these frequent nucleation events to biogenic precursors released by open water and melting sea ice regions. NPF events in the studied regions seem not to be related to bird colonies from coastal zones. Our results show a negative correlation (r = -0.89) between NPF events and sea ice extent, suggesting the impact of ultrafine Arctic aerosols is likely to increase in the future, given the likely increased sea ice melting. Understanding the composition and the sources of Arctic aerosols requires further integrated studies with joint multi-component ocean-atmosphere observation and modelling.

Substantial contribution of northern high-latitude sources to mineral dust in the Arctic.

In the Arctic, impurities in the atmosphere and cryosphere can strongly affect the atmospheric radiation and surface energy balance. While black carbon has hence received much attention, mineral dust has been in the background. Mineral dust is not only transported into the Arctic from remote regions but also, possibly increasingly, generated in the region itself. Here we study mineral dust in the Arctic based on global transport model simulations. For this, we have developed a dust mobilization scheme in combination with the Lagrangian particle dispersion model FLEXPART. A model evaluation, based on measurements of surface concentrations and annual deposition at a number of stations and aircraft vertical profiles, shows the suitability of this model to study global dust transport. Simulations indicate that about 3% of global dust emission originates from high-latitude dust sources in the Arctic. Due to limited convection and enhanced efficiency of removal, dust emitted in these source regions is mostly deposited closer to the source than dust from for instance Asia or Africa. This leads to dominant contributions of local dust sources to total surface dust concentrations (~85%) and dust deposition (~90%) in the Arctic region. Dust deposition from local sources peaks in autumn, while dust deposition from remote sources occurs mainly in spring in the Arctic. With increasing altitude, remote sources become more important for dust concentrations as well as deposition. Therefore, total atmospheric dust loads in the Arctic are strongly influenced by Asian (~38%) and African (~32%) dust, whereas local dust contributes only 27%. Dust loads are thus largest in spring when remote dust is efficiently transported into the Arctic. Overall, our study shows that contributions of local dust sources are more important in the Arctic than previously thought, particularly with respect to surface concentrations and dust deposition.

Fine-scale foraging behaviour of a medium-ranging marine predator.

1. Movement patterns of predators should allow them to detect and respond to prey patches at different spatial scales, particularly through the adoption of area-restricted search (ARS) behaviour. Here we use fine-scale movement and activity data combined with first-passage time (FPT) analysis to examine the foraging strategy of northern gannets Morus bassanus in the western North Sea, and to test the following hypotheses: (i) birds adopt a hierarchical foraging strategy characterized by nested ARS behaviour; (ii) the locations and characteristics of ARS zones are strongly influenced by physical oceanography; (iii) the initiation of ARS behaviour is triggered by the detection and pursuit of prey; (iv) ARS behaviour is strongly linked to increased foraging effort, particularly within nested ARS areas. 2. Birds on 13 of 15 foraging trips adopted ARS behaviour at a scale of 9.1 +/- 1.9 km, and birds on 10 of these 13 trips adopted a second, nested ARS scale of 1.5 +/- 0.8 km, supporting hypothesis 1 above. ARS zones were located 117 +/- 55 km from the colony and over half were within 5 km of a tidal mixing front ~50 km offshore, supporting hypothesis 2 above. 3. The initiation of ARS behaviour was usually followed after only a short time interval (typically ~5 min) by the commencement of diving. Gannets do not dive until after they have located prey, and so this pattern strongly suggests that ARS behaviour was triggered by prey detection, supporting hypothesis 3 above. However, ~33% of dives in mixed coastal water and 16% of dives in stratified water were not associated with any detectable ARS behaviour. Hence, while ARS behaviour resulted from the detection and pursuit of prey, encounters with prey species did not inevitably induce ARS behaviour. 4. Following the initiation of ARS behaviour, dive rates were almost four times higher within ARS zones than elsewhere and almost three times higher in zones with nested ARS behaviour than in those without, supporting hypothesis 4 above and suggesting that the foraging success of birds was linked to their ability to match the hierarchical distribution of prey.

A theoretical study of the oxidation of Hg0 to HgBr2 in the troposphere.

The oxidation of elemental mercury (Hg0) to the divalent gaseous mercury dibromide (HgBr2) has been proposed to account for the removal of Hg0 during depletion events in the springtime Arctic. The mechanism of this process is explored in this paper by theoretical calculations of the relevant rate coefficients. Rice-Ramsberger-Kassel-Marcus (RRKM) theory, together with ab initio quantum calculations where required, are used to estimate the following: recombination rate coefficients of Hg with Br, I, and O; the thermal dissociation rate coefficient of HgBr; and the recombination rate coefficients of HgBr with Br, I, OH, and O2. A mechanism based on the initial recombination of Hg with Br, followed by the addition of a second radical (Br, I, or OH) in competition with thermal dissociation of HgBr, is able to account for the observed rate of Hg0 removal, both in Arctic depletion events and at lower latitudes.

Improved hardware and software for single-crystal NMR spectroscopy.

Design of state-of-the-art instrumentation and software for acquisition and analysis of single-crystal NMR spectra is presented. The design involves highly accurate rotation of a goniometer, and the acquisition of all the spectra for each rotation axis is automatically controlled by the host computer of the spectrometer using a homebuilt interface between the computer and the single-crystal probe. Moreover, a software package (ASICS) for fast and routine assignment/analysis of complex single-crystal spectra has been developed. Employing this equipment, the acquisition and complete analysis of single-crystal NMR spectra may be performed in about the same time as required for powder methods (spinning or static). The hardware and software are compared to recent alternative approaches within single-crystal NMR. Finally, it has been observed that single-crystal NMR techniques may provide the desired data for samples where powder methods fail.

Front-door concentrations and personal exposures of Danish children to nitrogen dioxide.

The aims of the study were to evaluate the front-door concentration of traffic exhaust fumes as a surrogate for the personal exposure of children and to study factors in the behavior and the environment of children that affect their personal exposure to nitrogen dioxide (NO(2)). The exposure to NO(2) of 103 children living in Copenhagen and 101 children living in rural areas of Denmark was studied by measuring average concentrations over 1 week with diffusive badge samplers placed outside the front door of the home, inside the child's bedroom, and on each child. Detailed information about the activities of the children involving potential exposure to NO(2) was noted in diaries. The results indicated that the front-door concentration of traffic pollution might be used to classify the personal exposure of urban children, although misclassification would be introduced. Multiple regression analysis showed several factors that affected the personal NO(2) exposure of the children independently, including the front-door concentration, the bedroom concentration, time spent outdoors, gas appliances used at home, passive smoking, and burning candles.

Ambient air levels and the exposure of children to benzene, toluene, and xylenes in Denmark.

The aims of the study were to evaluate if the front-door concentrations of benzene, toluene, and xylenes can be used to classify the personal exposures of Danish children and to identify factors that affect their personal exposure. Average concentrations were measured over 1 week with diffusive samplers, and the personal exposures of 98 children and the concentrations outside the front doors of their homes were measured simultaneously. Time and activity patterns were noted in diaries. The front-door concentrations were significantly higher in Copenhagen than in rural areas (all P < 0.0001), but the personal exposures were only slightly higher. Even though the personal exposures were highly significantly associated with front-door concentrations in urban areas (all P < 0.004), use of the residential front-door concentration as an exposure surrogate would imply misclassification, as it cannot be used for rural children. Multiple regression analyses brought to light several factors that affect the exposure of children independently, including front-door concentration, riding in cars, and activities involving potential exposure to gasoline vapors like motocross, moped driving, and refueling of cars.

Exposure of Danish children to traffic exhaust fumes.

This exposure study addresses the validity of the exposure assessment method of an epidemiological study of traffic-related air pollution and childhood cancer. In particular, this paper concerns the question of whether the concentration of nitrogen dioxide (NO2) outside the front door is a valid marker of the exposure of the child living at the address. The study includes 100 children living on streets with dense traffic in central parts of Copenhagen and 100 children living in rural areas. Preliminary results, based on 25% of the study subjects, suggest that both the outdoor NO2-concentration and the exposure of the children are two to three times higher in Copenhagen than in the rural districts. Moreover, the results suggest that the NO2-concentration outside the front door is a poor marker of the exposure of the children in Copenhagen, but a marker of some relevance for the exposure of the children in rural districts. The preliminary results must be treated with caution, as among other things, the analysis did not consider seasonal changes and indoor NO2-sources such as passive smoking, candles, and gas appliances.

Mutational analysis of Moloney murine leukaemia virus surface protein gp70.

Ten mutations were generated in the env gene of Moloney murine leukaemia virus DNA. The mutations were made by site-directed mutagenesis to alter basic amino acids (lysine or arginine) in the surface glycoprotein gp70. Mutants were investigated following transfection into NIH/3T3 cells. All 10 mutants released virion particles into the medium, suggesting that none of the mutations affected overall viral gene expression or virion budding. Two mutants were positive in XC plaque assay, reverse transcriptase assay and re-infection experiments, showing that these mutations occurred in parts of the molecule not essential for infection. Three mutants were negative in both the XC plaque assay and re-infection experiments, suggesting that they make non-infectious virus particles. The results indicate a defect in the early phase of infection, perhaps in receptor binding or in the fusion of virion and host membranes. The other mutations resulted in reduced infectivity of released virion particles.

Retrovirus-induced cell fusion is enhanced by protease treatment.

The effect of proteases on retrovirus-induced cell fusion was studied. Both 'fusion from within' (fusion between infected and uninfected cells) and 'fusion from without' (fusion of uninfected cells by virus addition) was enhanced after treatment with proteases. An enhancement of up to 10-fold, giving 30% fusion of the cells, was observed. Protease treatment of infected cells or of virus particles enhanced fusion, indicating that cleavage of the virus surface proteins is important for cell fusion. Cell fusion is believed to reflect the virus-cell membrane fusion which occurs during the entry of enveloped viruses into cells. It is therefore possible that proteolytic cleavage of virus surface components during entry is involved in virus infection.

Intellectual impairment with regional cerebral dysfunction after low neonatal cerebral blood flow.

12 children, in whom neonatal CBF had been measured, were examined at the age of 9 to 10 years by means of clinical neurological examination, neuropsychologic tests and observations, and 133Xe single photon emission computed tomography (SPECT). Performance on most neuropsychologic tests or observations correlated with neonatal CBF but only rarely with other neonatal parameters (birthweight, gestational age, Apgar score at 5 min). Poor performance on each test or observation was in most instances correlated with a distinct pattern of regional cerebral dysfunction as assessed by SPECT. The dysfunctional region tended to be located periventricularly and in the watershed regions between major cerebral arteries. It is concluded that low neonatal cerebral perfusion may be an indicator, and possibly a determinant, of later intellectual dysfunction in stressed neonates, and that specific neuropsychologic deficits are associated with specific patterns of cerebral dysfunction in the present patient group.

Perinatal brain ischaemia: impact at four years of age.

A group of 15 children for whom cerebral blood flow (CBF) had been determined during the first few hours of life were examined between the ages of 3 years 9 months and four years. Clinical neurological and psychological (Stanford-Binet) tests were carried out and in three cases a computerised tomographic examination was made. Poor articulation, dysphasia, attention deficits and low IQ were found significantly more often among the five children with a documented episode of ischaemia (CBF less than 20 ml/100g/min) in the neonatal period. By summarizing the number of abnormal findings, the difference between the groups was found to be highly significant. It is concluded that ischaemia during the first hours of life is a critical determinant for the development of congitive disorders.

Low cerebral blood flow: a risk factor in the neonate.

Among 19 infants in whom cerebral blood flow had been determined a few hours after birth, four died during the first days or weeks after birth, all with massive intracranial hemorrhage. The other infants were examined at 9 to 12 1/2 months of age by means of clinical neurologic evaluation, developmental psychologic assessment (Cattell), EEG, and cranial computed tomography. Six of the ten infants who had had CBF of 20 ml/100 gm/minute or less had developed cerebral atrophy as demonstrated at autopsy or by CT scan, none with neonatal flows above 20 had done so. Only one in the low flow group had developed completely normally, whereas abnormal development was found in only a minority of the high flow group. No other neonatal observation had such a clear relationship to later development. It is concluded that CBF of 20 or less during the first hours of life is critical.