The El Niño–Southern Oscillation (ENSO) has been suggested
as a strong forcing in the methane cycle and as a driver of recent trends in
global atmospheric methane mole fractions CH4. Such a ...sensitivity
of the global CH4 budget to climate events would have important
repercussions for climate change mitigation strategies and the accuracy of
projections for future greenhouse forcing. Here, we test the impact of ENSO
on atmospheric CH4 in a correlation analysis. We use local and
global records of CH4, as well as stable carbon isotopic records
of atmospheric CH4 (δ13CH4), which are
particularly sensitive to the combined ENSO effects on CH4
production from wetlands and biomass burning. We use a variety of nominal,
smoothed, and detrended time series including growth rate records. We find
that at most 36 % of the variability in CH4 and
δ13CH4 is attributable to ENSO, but only for detrended
records in the southern tropics. Trend-bearing records from the southern
tropics, as well as all studied hemispheric and global records, show a minor
impact of ENSO, i.e. < 24 % of variability explained. Additional
analyses using hydrogen cyanide (HCN) records show a detectable ENSO
influence on biomass burning (up to 51 %–55 %), suggesting that it
is wetland CH4 production that responds less to ENSO than
previously suggested. Dynamics of the removal by hydroxyl likely counteract
the variation in emissions, but the expected isotope signal is not evident.
It is possible that other processes obscure the ENSO signal, which itself
indicates a minor influence of the latter on global CH4 emissions.
Trends like the recent rise in atmospheric CH4 can therefore not
be attributed to ENSO. This leaves anthropogenic methane sources as the
likely driver, which must be mitigated to reduce anthropogenic climate
change.
Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, ...obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings.
Many patients experiencing acute gastrointestinal bleeding (GIB) require iron supplementation to treat subsequent iron deficiency (ID) or iron‐deficiency anemia (IDA). Guidelines regarding management ...of these patients are lacking. We aimed to identify areas of unmet need in patients with ID/IDA following acute GIB in terms of patient management and physician guidance. We formed an international working group of gastroenterologists to conduct a narrative review based on PubMed and EMBASE database searches (from January 2000 to February 2021), integrated with observations from our own clinical experience. Published data on this subject are limited and disparate, and those relating to post‐discharge outcomes, such as persistent anemia and re‐hospitalization, are particularly lacking. Often, there is no post‐discharge follow‐up of these patients by a gastroenterologist. Acute GIB‐related ID/IDA, however, is a prevalent condition both at the time of hospital admission and at hospital discharge and is likely underdiagnosed and undertreated. Despite limited data, there appears to be notable variation in the prescribing of intravenous (IV)/oral iron regimens. There is also some evidence suggesting that, compared with oral iron, IV iron may restore iron levels faster following acute GIB, have a better tolerability profile, and be more beneficial in terms of quality of life. Gaps in patient care exist in the management of acute GIB‐related ID/IDA, yet further data from large population‐based studies are needed to confirm this. We advocate the formulation of evidence‐based guidance on the use of iron therapies in these patients, aiding a more standardized best‐practice approach to patient care.
Because self-assembly of matrix proteins is a key step in hard tissue mineralization, developing an understanding of the assembly pathways and underlying mechanisms is likely to be important for ...successful hard tissue engineering. While many studies of matrix protein assembly have been performed on bulk solutions, in vivo these proteins are likely to be in contact with charged biological surfaces composed of lipids, proteins, or minerals. Here we report the results of an in situ atomic force microscopy (AFM) study of self-assembly by amelogenin--the principal protein of the extracellular matrix in developing enamel--in contact with two different charged substrates: hydrophilic negatively charged bare mica and positively charged 3-aminopropyl triethoxysilane (APS) silanized mica. First we demonstrate an AFM-based protocol for determining the size of both amelogenin monomers and oligomers. Using this protocol, we find that, although amelogenin exists primarily as ~26 nm in diameter nanospheres in bulk solution at a pH of 8.0 studied by dynamic light scattering, it behaves dramatically differently upon interacting with charged substrates at the same pH and exhibits complex substrate-dependent assembly pathways and dynamics. On positively charged APS-treated mica surfaces, amelogenin forms a relatively uniform population of decameric oligomers, which then transform into two main populations: higher-order assemblies of oligomers and amelogenin monomers, while on negatively charged bare mica surfaces, it forms a film of monomers that exhibits tip-induced desorption and patterning. The present study represents a successful attempt to identify the size of amelogenin oligomers and to directly monitor assembly and disassembly dynamics on surfaces. The findings have implications for amelogenin-controlled calcium phosphate mineralization in vitro and may offer new insights into in vivo self-assembly of matrix proteins as well as their control over hard tissue formation.
Despite widespread monotherapy use of lamotrigine or levetiracetam during pregnancy, prospectively collected, blinded child development data are still limited. The NaME (Neurodevelopment of Babies ...Born to Mothers With Epilepsy) Study prospectively recruited a new cohort of women with epilepsy and their offspring for longitudinal follow-up.
Pregnant women of <21 weeks gestation (n = 401) were recruited from 21 hospitals in the UK. Data collection occurred during pregnancy (recruitment, trimester 3) and at 12 and 24 months of age. The primary outcome was blinded assessment of infant cognitive, language, and motor development on the Bayley Scales of Infant and Toddler Development (3rd edition) at 24 months of age with supplementary parent reporting on the Vinelands Adaptive Behavior Scales (2nd edition).
There were 394 live births, with 277 children (70%) completing the Bayley assessment at 24 months. There was no evidence of an association of prenatal exposure to monotherapy lamotrigine (-.74, SE = 2.9, 95% confidence interval CI = -6.5 to 5.0, p = .80) or levetiracetam (-1.57, SE = 3.1, 95% CI = -4.6 to 7.7, p = .62) with poorer infant cognition, following adjustment for other maternal and child factors in comparison to nonexposed children. Similar results were observed for language and motor scores. There was no evidence of an association between increasing doses of either lamotrigine or levetiracetam. Nor was there evidence that higher dose folic acid supplementation (≥5 mg/day) or convulsive seizure exposure was associated with child development scores. Continued infant exposure to antiseizure medications through breast milk was not associated with poorer outcomes, but the number of women breastfeeding beyond 3 months was low.
These data are reassuring for infant development following in utero exposure to monotherapy lamotrigine or levetiracetam, but child development is dynamic, and future follow-up is required to rule out later emerging effects.
Antigen-specific T cells play an essential role in immunoregulation and many diseases such as cancer. Characterizing the T cell receptor (TCR) sequences that encode T cell specificity is critical for ...elucidating the antigenic determinants of immunological diseases and designing therapeutic remedies. However, methods of obtaining single-cell TCR sequencing data are labor and cost intensive, typically requiring both cell sorting and full-length single-cell RNA-sequencing (scRNA-seq). New high-throughput 3' cell-barcoding scRNA-seq methods can simplify and scale this process; however, they do not routinely capture TCR sequences during library preparation and sequencing. While 5' cell-barcoding scRNA-seq methods can be used to examine TCR repertoire at single-cell resolution, doing so requires specialized reagents which cannot be applied to samples previously processed using 3' cell-barcoding methods.Here, we outline a method for sequencing TCRα and TCRβ transcripts from samples already processed using 3' cell-barcoding scRNA-seq platforms, ensuring TCR recovery at a single-cell resolution. In short, a fraction of the 3' barcoded whole transcriptome amplification (WTA) product typically used to generate a massively parallel 3' scRNA-seq library is enriched for TCR transcripts using biotinylated probes and further amplified using the same universal primer sequence from WTA. Primer extension using TCR V-region primers and targeted PCR amplification using a second universal primer result in a 3' barcoded single-cell CDR3-enriched library that can be sequenced with custom sequencing primers. Coupled with 3' scRNA-seq of the same WTA, this method enables simultaneous analysis of single-cell transcriptomes and TCR sequences which can help interpret inherent heterogeneity among antigen-specific T cells and salient disease biology. The method presented here can also be adapted readily to enrich and sequence other transcripts of interest from both 3' and 5' barcoded scRNA-seq WTA libraries.
Objective
This study was undertaken to assess the utility of the Ages and Stages Questionnaire–3rd Edition (ASQ‐3) and the Vineland Adaptive Behavior Scales–2nd Edition (VABS‐II) as ...neurodevelopmental screening tools for infants exposed to antiseizure medications in utero, and to examine their suitability for use in large‐population signal generation initiatives.
Methods
Participants were women with epilepsy who were recruited from 21 hospitals in England and Northern Ireland during pregnancy between 2014 and 2016. Offspring were assessed at 24 months old using the Bayley Scales of Infant Development–3rd Edition (BSID‐III), the VABS‐II, and the ASQ‐3 (n = 223). The sensitivity and specificity of the ASQ‐3 and VABS‐II to identify developmental delay at 24 months were examined, using the BSID‐III to define cases.
Results
The ASQ‐3 identified 65 children (29.1%) as at risk of developmental delay at 24 months using standard referral criteria. Using a categorical approach and standard referral criteria to identify delay in the ASQ‐3 and BSID‐III at 24 months, the ASQ‐3 showed excellent sensitivity (90.9%) and moderate specificity (74.1%). Utilizing different cut‐points resulted in improved properties and may be preferred in certain contexts. The VABS‐II exhibited the strongest psychometric properties when borderline impairment (>1 SD below the mean) was compared to BSID‐III referral data (sensitivity = 100.0%, specificity = 96.6%).
Significance
Both the ASQ‐3 and VABS‐II have good psychometric properties in a sample of children exposed to antiseizure medications when the purpose is the identification of at‐risk groups. These findings identify the ASQ‐3 as a measure that could be used effectively as part of a tiered surveillance system for teratogenic exposure by identifying a subset of individuals for more detailed investigations. Although the VABS‐II has excellent psychometric properties, it is more labor‐intensive for both the research team and participants and is available in fewer languages than the ASQ‐3.
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