Petrogenetic processes in the ultramafic, alkaline and carbonatitic magmatism in the Kola Alkaline Province: a review

Igneous rocks of the Devonian Kola Alkaline Carbonatite Province (KACP) in NW Russia and eastern Finland can be classified into four groups: (a) primitive mantle-derived silica-undersaturated silicate magmas; (b) evolved alkaline and nepheline syenites; (c) cumulate rocks; (d) carbonatites and phoscorites, some of which may also be cumulates. There is no obvious age difference between these various groups, so all of the magma-types were formed at the same time in a relatively restricted area and must therefore be petrogenetically related. Both sodic and potassic varieties of primitive silicate magmas are present. On major element variation diagrams, the cumulate rocks plot as simple mixtures of their constituent minerals (olivine, clinopyroxene, calcite etc). There are complete compositional trends between carbonatites, phoscorites and silicate cumulates, which suggests that many carbonatites and phoscorites are also cumulates. CaO/Al2O3 ratios for ultramafic and mafic silicate rocks in dykes and pipes range up to 5, indicating a very small degree of melting of a carbonated mantle at depth. Damkjernites appear to be transitional to carbonatites. Trace element modelling indicates that all the mafic silicate magmas are related to small degrees of melting of a metasomatised garnet peridotite source. Similarities of the REE patterns and initial Sr and Nd isotope compositions for ultramafic alkaline silicate rocks and carbonatites indicate that there is a strong relationship between the two magma-types. There is also a strong petrogenetic link between carbonatites, kimberlites and alkaline ultramafic lamprophyres. Fractional crystallisation of olivine, diopside, melilite and nepheline gave rise to the evolved nepheline syenites, and formed the ultramafic cumulates. All magmas in the KACP appear to have originated in a single event, possibly triggered by the arrival of hot material (mantle plume?) beneath the Archaean/Proterozoic lithosphere of the northern Baltic Shield that had been recently metasomatised. Melting of the carbonated garnet peridotite mantle formed a spectrum of magmas including carbonatite, damkjernite, melilitite, melanephelinite and ultramafic lamprophyre. Pockets of phlogopite metasomatised lithospheric mantle also melted to form potassic magmas including kimberlite. Depth of melting, degree of melting and presence of metasomatic phases are probably the major factors controlling the precise composition of the primary melts formed

Visualizing the interaction of Acanthamoeba castellanii with human retinal epithelial cells by spontaneous Raman and CARS imaging

Improved understanding of the mechanism of nutrient’s uptake can enable targeted manipulation of nutrient sensing pathways in medically important pathogens to a greater degree than is currently possible. In this context, we present the use of spontaneous Raman micro-spectroscopy (RMS) and coherent anti-Stokes Raman spectroscopy (CARS) to visualise the time-dependent molecular interactions between the protozoan Acanthamoeba castellanii and host human cells. Human retinal pigment epithelial (ARPE-19) cells were prelabelled with deuterated Phe (L-Phe(D8)) and the uptake of the host derived L-Phe(D8) by A. castellanii trophozoites was measured by RMS for up to 48 hours post infection (hpi). This approach revealed a time-dependent uptake pattern of this essential amino acid by A. castellanii trophozoites during the first 24 hpi with complete enrichment with L-Phe(D8) detected in trophozoites at 48 hpi. In contrast, cell free A. castellanii trophozoites showed a modest uptake of only 16-18% L-Phe(D8) from L-Phe(D8)–supplemented culture medium after 3h, 24h and 48h hpi. CARS microscopy was successfully used to monitor the reprogramming of lipids within the trophozoites as they engaged with host cells. The methodology presented here provides new advances in the ability to analyze the kinetic of amino acid acquisition by A. castellanii from host cell and extracellular environment, and to visualize lipid reprogramming within the trophozoite

In vivo imaging of the tumor and its associated microenvironment using combined CARS / 2-photon microscopy

The use of confocal and multi-photon microscopy for intra-vital cancer imaging has impacted on our understanding of cancer cell behavior and interaction with the surrounding tumor microenvironment in vivo. However, many studies to-date rely on the use fluorescent dyes or genetically encoded probes that enable visualization of a structure or cell population of interest, but do not illuminate the complexity of the surrounding tumor microenvironment. Here, we show that multi-modal microscopy combining 2-photon fluorescence with CARS can begin to address this deficit, enabling detailed imaging of the tumor niche without the need for additional labeling. This can be performed on live tumor-bearing animals through optical observation windows, permitting real-time and longitudinal imaging of dynamic processes within the tumor niche

A search for AGN in the most extreme UV-selected starbursts using the European VLBI Network

We have used the European VLBI Network (EVN) to observe a sample of Lyman Break Analogs (LBAs), nearby (z < 0.3) galaxies with properties similar to the more distant Lyman Break Galaxies (LBGs). The study of LBGs may help define the feed-back relationship between black holes (BHs) and their host galaxies. Previous VLA observations have shown that the kpc-scale radio emission from LBAs is dominated by starbursts. The main targets of this VLBI experiment were selected because they possessed emission-line properties between starbursts and Type 2 (obscured) AGN. Eight targets (three star-forming LBAs, four composite LBAs, and one Type 1 AGN) were observed at 5 GHz, four of which were also observed at 1.7 GHz. One star-forming LBA and one composite LBA were detected above 5 \sigma at 1.7 GHz (only), while the AGN was detected at 5 GHz. In both LBAs, the radio luminosity (LR) exceeds that expected from supernovae (remnants) based on a comparison with Arp220, Arp229A and Mrk273, by factors of 2 - 8. The composite LBA exhibits a compact core emitting around 10% of the VLA flux density. The high Tb of 3.5E7 K and excess core L_R with respect to the L_R/L_X relation of radio-quiet AGN indicate that this LBA possesses an obscured AGN (MBH ~ E5-E7 M_sun). While weak AGN may co-exist with the starbursts as shown in at least one of the LBAs, their contribution to the total radio flux is fairly minimal. Our results show that the detection of such weak AGN presents a challenge at radio, X-ray and optical emission-line wavelengths at z ~ 0.2, indicating the great difficulties that need to be overcome in order to study similar processes at high redshift when these types of galaxies were common.Comment: 10 pages, 4 figures, accepted for publication in MNRA

The Many Faces of Fear: Comparing the Pathways and Impacts of Nonconsumptive Predator Effects on Prey Populations

Background: Most ecological models assume that predator and prey populations interact solely through consumption: predators reduce prey densities by killing and consuming individual prey. However, predators can also reduce prey densities by forcing prey to adopt costly defensive strategies. Methodology/Principal Findings: We build on a simple Lotka-Volterra predator-prey model to provide a heuristic tool for distinguishing between the demographic effects of consumption (consumptive effects) and of anti-predator defenses (nonconsumptive effects), and for distinguishing among the multiple mechanisms by which anti-predator defenses might reduce prey population growth rates. We illustrate these alternative pathways for nonconsumptive effects with selected empirical examples, and use a meta-analysis of published literature to estimate the mean effect size of each pathway. Overall, predation risk tends to have a much larger impact on prey foraging behavior than measures of growth, survivorship, or fecundity. Conclusions/Significance: While our model provides a concise framework for understanding the many potential NCE pathways and their relationships to each other, our results confirm empirical research showing that prey are able to partially compensate for changes in energy income, mitigating the fitness effects of defensive changes in time budgets. Distinguishing the many facets of nonconsumptive effects raises some novel questions, and will help guide both empirica

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Point-of-care testing in paediatric settings in the UK and Ireland: A cross-sectional study

Background: Point-of-care testing (POCT) is diagnostic testing performed at or near to the site of the patient. Understanding the current capacity, and scope, of POCT in this setting is essential in order to respond to new research evidence which may lead to wide implementation. Methods: A cross-sectional online survey study of POCT use was conducted between 6th January and 2nd February 2020 on behalf of two United Kingdom (UK) and Ireland-based paediatric research networks (Paediatric Emergency Research UK and Ireland, and General and Adolescent Paediatric Research UK and Ireland). Results: In total 91/109 (83.5%) sites responded, with some respondents providing details for multiple units on their site based on network membership (139 units in total). The most commonly performed POCT were blood sugar (137/139; 98.6%), urinalysis (134/139; 96.4%) and blood gas analysis (132/139; 95%). The use of POCT for Influenza/Respiratory Syncytial Virus (RSV) (45/139; 32.4%, 41/139; 29.5%), C-Reactive Protein (CRP) (13/139; 9.4%), Procalcitonin (PCT) (2/139; 1.4%) and Group A Streptococcus (5/139; 3.6%) and was relatively low. Obstacles to the introduction of new POCT included resources and infrastructure to support test performance and quality assurance. Conclusion: This survey demonstrates significant consensus in POCT practice in the UK and Ireland but highlights specific inequity in newer biomarkers, some which do not have support from national guidance. A clear strategy to overcome the key obstacles of funding, evidence base, and standardising variation will be essential if there is a drive toward increasing implementation of POCT