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Early childhood developmental concerns following SARS-CoV-2 infection and COVID-19 vaccination during pregnancy:A Scottish population-level retrospective cohort study
Get PDFObjectives: Understanding the effects of SARS-CoV-2 infection and COVID-19 vaccination during pregnancy can help inform clinical guidance and tackle vaccine hesitancy. We examined relationships between SARS-CoV-2 infection during pregnancy, COVID-19 vaccination during pregnancy, and early child developmental concerns in children age 13–15 months in Scotland.Method: We created a large population-level linked administrative health dataset, combining the COVID-19 in Pregnancy in Scotland (COPS) dataset with age 13–15 month child health review data and other datasets. We included children conceived after May 18, 2020, and born before Sept 30, 2021, and their mothers. We used logistic regression modelling to investigate associations between SARS-CoV-2 infection during pregnancy, COVID-19 vaccination during pregnancy, and developmental concerns (ie, parent or caregiver developmental concerns and health visitor-identified concerns regarding speech–language–communication, problem solving, gross motor, personal–social, and emotional–behavioural development) measured during routine child health reviews at age 13–15 months.Results: A total of 24 919 child–mother pairs (12 752 [51·2%] male children; 12 167 [48·8%] female children) were included. 1631 (6·5%) children were prenatally exposed to SARS-CoV-2 and 4943 (19·8%) to COVID-19 vaccination. We found no associations between SARS-CoV-2 infection during pregnancy and developmental concerns. After confounder and covariate adjustment, COVID-19 vaccination during pregnancy was associated with reduced odds of developmental concerns regarding problem solving (odds ratio 0·78 [95% CI 0·64–0·95]), personal–social (0·76 [0·61–0·95]), and emotional–behavioural (0·67 [0·48–0·92]) development, but had no associations with other developmental concerns.Conclusion: SARS-CoV-2 infections during pregnancy do not appear to be linked to early childhood developmental concerns, and COVID-19 vaccinations during pregnancy are safe from the perspective of early childhood developmental concerns. As some developmental concerns do not become apparent until children are older than 13–15 months, future research should continue to monitor outcomes as children grow and develop
Innovations in post-pregnancy contraception
Get PDFEvidence indicates that regardless of how a pregnancy ends (birth, abortion, miscarriage, ectopic), that ovulation resumes quickly in most cases. Those who are sexually active soon afterwards therefore require an effective method of contraception to avoid an unintended pregnancy. Yet, lack of knowledge on contraceptive options or when they can or should be initiated can be barriers to starting a method. For those who have given birth the requirements of looking after a newborn and recovering from delivery adds to existing barriers of accessing a chosen method after pregnancy. It is vital therefore that access to contraception can be facilitated for women to start immediately post pregnancy. this chapter will outline some initiatives to empower individuals to choose contraception for following a pregnancy and also innovations to help them access that method
Dynamic patterns of gene expression match extracellular signals through push-pull regulation
Get PDFCells can match gene expression to a range of a particular signal. For example, budding yeast expresses at least seven hexose-transporter (HXT) genes in different concentration ranges of extracellular glucose. Using time-lapse microscopy, microfluidics, dynamic glucose inputs, and mathematical modelling, we determine how this glucose matching of HXT expression occurs mechanistically. The glucose-sensing network generates a push-pull regulation using two pairs of regulators: rising glucose weakens, or “pulls”, repression via regulators Mth1 and Std1 while simultaneously strengthening, or “pushing”, repression via regulators Mig1 and Mig2; falling glucose reverses this push-pull. The regulators’ combined activity reports extracellular glucose. Cells match HXT expression to glucose because HXT promoters couple to the regulators in ways specific to low, medium, or high-affinity transporters. By rewiring transcription and using model-predicted perturbations, we demonstrate how an HXT encoding a medium-affinity transporter can respond as one encoding either a low- or a high-affinity transporter. Matching gene expression to a pattern of input is fundamental; we believe push-pull regulation to be widespread
High resolution land use maps from 1960 to 2100
Get PDFAnthropogenic land-use and land-cover change is a major driver of climate change and biodiversity loss. Land-use and land-cover change also leads to changes in the spatial pattern of Earth’s landscapes, which have further negative impacts on environmental processes. For example, deforestation can increase the distance between forest patches, making it harder for species to move between them. Harmonized land-use and land-cover datasets contain standardized maps of global land use and land cover through time, without any gaps or sudden changes between historic and future periods. Harmonized datasets are important for addressing the negative consequences of land-use and land-cover change because they are used in environmental models to predict its impacts on processes such as carbon emissions and species movement. However, existing harmonized datasets do not project the spatial pattern of land-use and land-cover change into the future and have coarse resolutions that do not match the fine scales on which environmental processes occur. We present a high-resolution, global-scale harmonized land-use and land-cover dataset for five future scenarios that spans the period 1960–2100. The spatial pattern of land-use and land-cover change was accounted for when generating the future maps to ensure that they have realistic spatial patterns. This new dataset will be suitable for integration with a range of environmental models, such as those that model biodiversity, climate, and fire, and therefore offers an important tool for understanding the effects of land-use and land-cover change and developing solutions to environmental challenges
Genome-wide gene-environment interaction study uncovers 162 vitamin D status variants using a precise ambient UVB measure
Get PDFVitamin D status is influenced by genetic and environmental factors – primarily sun exposure. Using satellite weather data, we estimated an ambient UVB dose for each participant based on residential address and date of sampling. We conducted genome-wide tests in 338,977 UK Biobank White British participants, adjusted for age, sex, supplements, UVB dose, and 10 principal components to account for population structure. We applied three models to test for genetic effects: marginal only, main and interaction, and joint effects. We identified 307 variants associated with standardized log-transformed 25-hydroxyvitamin D (25OHD) concentration, 162 of which were not previously identified in GWAS. We identify an increase in SNP-heritability by increasing ambient UVB exposure quintiles (h2Q1=8.48% vs. h2Q5=15.56%). Downstream annotation implicated genes in the 25OHD pathway, including the circadian regulator, BMAL1. This and further findings suggest that vitamin D status and circadian rhythm may be entangled and that vitamin D metabolites may have a role as mediators of seasonal physiological fluctuations, including metabolism, and in turn explain the established associations with lipid metabolism pathways
Molecular profiling and tumour biomarker analysis of GOG281/LOGS: a positive late-phase trial of trametinib for recurrent/persistent low grade-serous ovarian carcinoma
Get PDFPurpose: Low-grade serous ovarian carcinoma (LGSOC) is a distinct form of ovarian cancer characterised by younger patient age and relative chemoresistance. The GOG281/LOGS trial (NCT02101788) investigated the efficacy of the MEK inhibitor trametinib compared to physician’s choice standard of care (SOC) in LGSOC patients with persistent/recurrent disease. The study demonstrated significantly improved progression-free survival (PFS) in the trametinib-treated arm.Experimental Design: 260 patients with recurrent/persistent LGSOC were enrolled and randomised in GOG281. We performed molecular analysis of 170 patients with available tumour specimens, comprising whole exome sequencing and phospho-ERK immunohistochemistry, to identify biomarkers of clinical benefit from trametinib. The demographics of the translational cohort (n=170) were comparable to the total trial cohort. Results: High tumour pERK expression (greater than the median histoscore of 140) was associated with significantly prolonged PFS with trametinib treatment versus SOC (median 20.1 vs 5.6 months, log-rank P<0.0001; test for interaction P=0.023). Tumours harbouring canonical RAS-RAF-MAPK mutations (KRAS/BRAF/NRAS: 44/134, 32.8% of cases) had a higher response rate to trametinib (50.0% vs 8.3%; Barnard’s P=0.0004; test for interaction P=0.054), but KRAS/BRAF/NRAS status was not predictive of prolonged PFS (test for interaction P=0.719). KRAS amplification (n=5 without KRAS/NRAS/BRAF mutation) and mutation of MAPK-associated genes (n=25 without KRAS/NRAS/BRAF mutation or KRAS copy-number gain) expanded the number of cases with identifiable MAPK defects to 55.2%, but consideration of these events did not improve the discrimination of trametinib responders. Chr1p loss (49% cases) was associated with lower pERK expression (P=0.021).Conclusion: This exploratory analysis suggests pERK expression and mutation of KRAS/BRAF/NRAS are candidate biomarkers of improved PFS and response to trametinib, respectively. <br/
Centuries of compounding human influence on Amazonian forests
Get PDFRecent evidence suggests that the ecological footprints of pre-Columbian Indigenous peoples in Amazonia persist in modern forests. Ecological impacts resulting from European colonization c. 1550 CE and the Amazonian Rubber Boom c. 1850 to 1920 CE are largely unexplored but could be important additive influences on forest structure and tree species composition. Using environmental niche models, we show the highest probabilities of pre-Columbian and colonial occupation sites, and hence human-induced ecological influences, occurred in forests along rivers. In many areas, the predicted pre-Columbian and colonial distributions overlap spatially with the potential for superimposed ecological influences. Environmental gradients are known to structure Amazonian vegetation composition, but they are also strong predictors of past human influence, both spatially and temporally. Our comparisons of model outputs with relative abundances of Amazonian tree species suggest that pre-Columbian and colonial-period ecological legacies are associated with modern forest composition
Megafauna of the RMS Titanic shipwreck and a nearby seamount ridge in the deep sea of the western North Atlantic
Get PDFThe biology of shipwrecks and hard substrata in the deep sea remains poorly explored. These complex habitats alter biodiversity on the deep seafloor and facilitate connecting populations over large distances. We analysed biological and environmental data collected at the RMS Titanic wreck site (3800 m) and a seamount ridge (2900 m) during the 2022 Titanic Expedition (15 June–25 July). The ridge is part of Seamount U, approximately 40 km southeast of the Titanic, and was explored for the first time on July 23, 2022. We analysed megafaunal occurrence across 920 images of the wreck site and 169 images of the ridge site, from digital video. The most common megafauna overall were Ophiuroidea, Munidopsis sp., Cushion-Encrusting Porifera, Geodia spp., and cold-water corals including Keratoisididae and Pennatuloidea. We describe the patterns in community composition across five benthic habitats, likely controlled by substrate type, local hydrodynamics, and food availability. The ridge yielded a higher number of observed megafauna and higher Shannon diversity (n = 73; H = 2.89) than the wreck (n = 21; H = 1.39). The communities associated with the ridge showed high dissimilarity to those at the wreck. We also explored the temporal variability of biofouling organisms on the Titanic using video from 1986 to 2022. We observed a net increase in Chrysogorgia sp. and Lepidisis sp. coral colonies over time with estimated average linear growth rates of up to 10 mm/yr and linear rusticle extensions of up to 14 mm/yr, raising questions about the wreck's ecological succession as it deteriorates.</p
Diagnostics at the frontline: using the Public Accounts Committee report to catalyse the UK’s antimicrobial resistance diagnostics strategy
Get PDFBetween 2020 and 2024, the UK Government spent £567 million1 on its programme for tackling the growing threat of antimicrobial resistance (AMR), of which £543 million was allocated to the Department of Health and Social Care, National Health Service England, and UK Health Security Agency. On June 13, 2025, the UK Public Accounts Committee (PAC), which scrutinises government spending, published a review evaluating the effectiveness of this spending to address AMR risks through the measures set out in the national action plan (NAP).
Ultra-efficient label-free cell death detection based on multifunctional colorimetric fluorescent in-situ silver nanocluster/graphene nanohybridzyme and its application in environmental biological samples and cellular imaging
Get PDFAgNCs/graphene NHZs) was designed and employed for dual-modal naked-eye colorimetric and fluorometric detection of cell death biomarkers involved in ferroptosis, cuproptosis, and apoptosis. The interesting feature of developed NHZs is the colorimetric speciation of “turn-on” Fe2+, Cu2+, and Cyt c and “turn-off” cysteine (Cys) and glutathione (GSH), and its speciation ability of Fe2+ from Fe3+as well. The presence of analytes causes a colorimetric limit of detection of 10.8–191 nM and fluorometric detection limit from 0.25 to 121 nM in the appropriate linear ranges, with fast times ranging 5–20 min. The designed NHZs were successfully employed for fluorescence imaging of HT29 human colon cancer and also quantitatively validated in just 2 μL of cell lysates, environmental, and biological samples. Compared to the semi-quantitative conventional Western blot and other cell death assays, the novelty of presented probe is low cost, simple preparation, high sensitivity, multifunctionallity, and dual-modality with the speciation and quantitative ability without using any targeting agent, which makes it appropriate for dual-modal tracking cell death processes and drug evaluation in a very short tim
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