Does the use of a vascular contrast agent facilitate earlier detection of maternal flow to the placental intervillous space (IVS) in the first trimester of pregnancy?
Microvascular filling of the IVS ...was demonstrated by contrast-enhanced ultrasound from 6 weeks of gestation onwards, earlier than previously believed.
During placental establishment and remodeling of maternal spiral arteries, endovascular trophoblast cells invade and accumulate in the lumen of these vessels to form 'trophoblast plugs'. Prior evidence from morphological and Doppler ultrasound studies has been conflicting as to whether the spiral arteries are completely plugged, preventing maternal blood flow to the IVS until late in the first trimester.
Uteroplacental flow was examined across the first trimester in human subjects given an intravenous infusion of lipid-shelled octofluoropropane microbubbles with ultrasound measurement of destruction and replenishment kinetics. We also performed a comprehensive histopathological correlation using two separately archived uteroplacental tissue collections to evaluate the degree of spiral artery plugging and evaluate remodeling of the upstream myometrial radial and arcurate arteries.
Pregnant women (n = 34) were recruited in the first trimester (range: 6+3 to 13+6 weeks gestation) for contrast-enhanced ultrasound studies with destruction-replenishment analysis of signal intensity for assessment of microvascular flux rate. Histological samples from archived in situ (Boyd Collection, n = 11) and fresh first, second, and third trimester decidual and post-hysterectomy uterine specimens (n = 16) were evaluated by immunohistochemistry (using markers of epithelial, endothelial and T-cells, as well as cell adhesion and proliferation) and ultrastructural analysis.
Contrast agent entry into the IVS was visualized as early as 6+3 weeks of gestation with some variability in microvascular flux rate noted in the 6-7+6 week samples. Spiral artery plug canalization was observed from 7 weeks with progressive disintegration thereafter. Of note, microvascular flux rate did not progressively increase until 13 weeks, which suggests that resistance to maternal flow in the early placenta may be mediated more proximally by myometrial radial arteries that begin remodeling at the end of the first trimester.
Gestational age was determined by crown-rump length measurements obtained by transvaginal ultrasound on the day of contrast-enhanced imaging studies, which may explain the variability in the earliest gestational age samples due to the margin of error in this type of measurement.
Our comprehensive in situ histological analysis, in combination with the use of an in vivo imaging modality that has the sensitivity to permit visualization of microvascular filling, has allowed us to reveal new evidence in support of increasing blood flow to the IVS from 6 weeks of gestation. Histologic review suggested the mechanism may be blood flow through capillary-sized channels that form through the loosely cohesive 'plugs' by 7 weeks gestation. However, spiral artery remodeling on its own did not appear to explain why there is significantly more blood flow at 13 weeks gestation. Histologic studies suggest it may be related to radial artery remodeling, which begins at the end of the first trimester.
This project was supported by the Oregon Health and Science University Knight Cardiovascular Institute, Center for Developmental Health and the Struble Foundation. There are no competing interests.
Recent studies clarify where the most vulnerable species live, where and how humanity changes the planet, and how this drives extinctions. We assess key statistics about species, their distribution, ...and their status. Most are undescribed. Those we know best have large geographical ranges and are often common within them. Most known species have small ranges. The numbers of small-ranged species are increasing quickly, even in well-known taxa. They are geographically concentrated and are disproportionately likely to be threatened or already extinct. Current rates of extinction are about 1000 times the likely background rate of extinction. Future rates depend on many factors and are poised to increase. Although there has been rapid progress in developing protected areas, such efforts are not ecologically representative, nor do they optimally protect biodiversity.
For more than a decade, scientists have argued about the warmth of the current interglaciation. Was the warmth of the preindustrial late Holocene natural in origin, the result of orbital changes that ...had not yet driven the system into a new glacial state? Or was it in considerable degree the result of humans intervening in the climate system through greenhouse gas emissions from early agriculture? Here we summarize new evidence that moves this debate forward by testing both hypotheses. By comparing late Holocene responses to those that occurred during previous interglaciations (in section 2), we assess whether the late Holocene responses look different (and thus anthropogenic) or similar (and thus natural). This comparison reveals anomalous (anthropogenic) signals. In section 3, we review paleoecological and archaeological syntheses that provide ground truth evidence on early anthropogenic releases of greenhouse gases. The available data document large early anthropogenic emissions consistent with the anthropogenic ice core anomalies, but more information is needed to constrain their size. A final section compares natural and anthropogenic interpretations of the δ13C trend in ice core CO2.
Key Points
Holocene ice core and ocean sediment trends are anomalous compared to previous interglaciations
Paleoecology and archaeology show that early farmers emitted large amounts of CO2 and CH4
Large early agricultural emissions are consistent with geochemical constraints
We present the fourth in a series of catalogs of gamma-ray bursts (GRBs) observed with Fermi's Gamma-ray Burst Monitor (Fermi-GBM). It extends the six year catalog by four more years, now covering ...the 10 year time period from trigger enabling on 2008 July 12 to 2018 July 11. During this time period GBM triggered almost twice a day on transient events, 2356 of which we identified as cosmic GRBs. Additional trigger events were due to solar flare events, magnetar burst activities, and terrestrial gamma-ray flashes. The intention of the GBM GRB catalog series is to provide updated information to the community on the most important observables of the GBM-detected GRBs. For each GRB the location and main characteristics of the prompt emission, the duration, peak flux, and fluence are derived. The latter two quantities are calculated for the 50-300 keV energy band, where the maximum energy release of GRBs in the instrument reference system is observed and also for a broader energy band from 10-1000 keV, exploiting the full energy range of GBM's low-energy detectors. Furthermore, information is given on the settings of the triggering criteria and exceptional operational conditions during years 7 to 10 in the mission. This fourth catalog is an official product of the Fermi-GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center.
8000 years ago, prior to Neolithic agriculture, Europe was mostly a wooded continent. Since then, its forest cover has been progressively fragmented, so that today it covers less than half of ...Europe's land area, in many cases having been cleared to make way for fields and pasture-land. Establishing the origin of Europe's current, more open land-cover mosaic requires a long-term perspective, for which pollen analysis offers a key tool. In this study we utilise and compare three numerical approaches to transforming pollen data into past forest cover, drawing on >1000
C-dated site records. All reconstructions highlight the different histories of the mixed temperate and the northern boreal forests, with the former declining progressively since ~6000 years ago, linked to forest clearance for agriculture in later prehistory (especially in northwest Europe) and early historic times (e.g. in north central Europe). In contrast, extensive human impact on the needle-leaf forests of northern Europe only becomes detectable in the last two millennia and has left a larger area of forest in place. Forest loss has been a dominant feature of Europe's landscape ecology in the second half of the current interglacial, with consequences for carbon cycling, ecosystem functioning and biodiversity.
Methods for analyzing chromosome conformation in mammalian cells are either low resolution or low throughput and are technically challenging. In next-generation (NG) Capture-C, we have redesigned the ...Capture-C method to achieve unprecedented levels of sensitivity and reproducibility. NG Capture-C can be used to analyze many genetic loci and samples simultaneously. High-resolution data can be produced with as few as 100,000 cells, and single-nucleotide polymorphisms can be used to generate allele-specific tracks. The method is straightforward to perform and should greatly facilitate the investigation of many questions related to gene regulation as well as the functional dissection of traits examined in genome-wide association studies.
The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) disease (COVID-19) pandemic has caused millions of deaths worldwide. Genome-wide association studies identified the 3p21.31 region as ...conferring a twofold increased risk of respiratory failure. Here, using a combined multiomics and machine learning approach, we identify the gain-of-function risk A allele of an SNP, rs17713054G>A, as a probable causative variant. We show with chromosome conformation capture and gene-expression analysis that the rs17713054-affected enhancer upregulates the interacting gene, leucine zipper transcription factor like 1 (LZTFL1). Selective spatial transcriptomic analysis of lung biopsies from patients with COVID-19 shows the presence of signals associated with epithelial-mesenchymal transition (EMT), a viral response pathway that is regulated by LZTFL1. We conclude that pulmonary epithelial cells undergoing EMT, rather than immune cells, are likely responsible for the 3p21.31-associated risk. Since the 3p21.31 effect is conferred by a gain-of-function, LZTFL1 may represent a therapeutic target.
On 2017 August 17 at 12:41:06 UTC the Fermi Gamma-ray Burst Monitor (GBM) detected and triggered on the short gamma-ray burst (GRB) 170817A. Approximately 1.7 s prior to this GRB, the Laser ...Interferometer Gravitational-wave Observatory triggered on a binary compact merger candidate associated with the GRB. This is the first unambiguous coincident observation of gravitational waves and electromagnetic radiation from a single astrophysical source and marks the start of gravitational-wave multi-messenger astronomy. We report the GBM observations and analysis of this ordinary short GRB, which extraordinarily confirms that at least some short GRBs are produced by binary compact mergers.
Abstract
We present the systematic spectral analyses of gamma-ray bursts (GRBs) detected by the Fermi Gamma-Ray Burst Monitor during its first ten years of operation. This catalog contains two types ...of spectra: time-integrated spectral fits and spectral fits at the brightest time bin, from 2297 GRBs, resulting in a compendium of over 18,000 spectra. The four different spectral models used for fitting the spectra were selected based on their empirical importance to the shape of many GRBs. We describe in detail our procedure and criteria for the analyses, and present the bulk results in the form of parameter distributions both in the observer frame and in the GRB rest frame. 941 GRBs from the first four years have been refitted using the same methodology as that of the 1356 GRBs in years five through ten. The data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center.
ABSTRACT We report on the analysis of two deep XMM-Newton observations of the magnetar Swift J1834.9−0846 and its surrounding extended emission taken in 2014 March and October, 2.5 and 3.1 yr after ...the source went into outburst. The magnetar is only weakly detected in the first observation, with an absorption-corrected flux erg s−1 cm−2 and a upper limit during the second observation of about 3 × 10−14 erg s−1 cm−2. This flux level is more than 3 orders of magnitude lower than the flux measured at the outburst onset in 2011 September. The extended emission, centered at the magnetar position and elongated toward the southwest, is clearly seen in both observations; it is best fit by a highly absorbed power law (PL), with a hydrogen column density of cm−2 and PL photon index . Its flux is constant between the two observations at erg s−1 cm−2. We find no statistically significant changes in the spectral shape or the flux of this extended emission over a period of 9 yr from 2005 to 2014. These new results strongly support the extended emission nature as a wind nebula and firmly establish Swift J1834.9−0846 as the first magnetar to show a surrounding wind nebula. Further, our results imply that such nebulae are no longer exclusive to rotation-powered pulsars and narrow the gap between these two subpopulations of isolated neutron stars. The size and spectrum of the nebula are compatible with those of pulsar-wind nebulae, but its radiative efficiency is markedly high, possibly pointing to an additional wind component in Swift J1834.9−0846.