Quantitative elemental mapping of granulite-facies monazite: Textural insights and implications for petrochronology

Texturally complex monazite grains contained in two granulite-facies pelitic migmatites from southern Baffin Island, Arctic Canada, were mapped by laser ablation-inductively coupled plasma-mass spectrometry (using spot sizes < 5 µm) to quantitatively determine the spatial variation in trace element chemistry (with up to 1883 analyses per grain). The maps highlight the chemical complexity of monazite grains that have experienced multiple episodes of growth, resorption and chemical modification by dissolution-precipitation during high-grade metamorphism. Following detailed chemical characterisation of monazite compositional zones, a related U-Pb dataset is re-interpreted, allowing petrologically-significant ages to be extracted from a continuum of concordant data. Synthesis of these data with pseudosection modelling of prograde and peak conditions allows for the temporal evolution of monazite trace element chemistry to be placed in the context of the evolving P-T conditions and major phase assemblage. This approach enables a critical evaluation of three commonly used petrochronological indicators: linking Y to garnet abundance, the Eu anomaly to feldspar content, and Th/U to anatectic processes. Europium anomalies and Th/U behave in a relatively systematic fashion, suggesting that they are reliable petrochronological witnesses. However, Y systematics are variable, both within domains interpreted to have grown in a single event, between grains interpreted to be part of the same age population, and between samples that experienced similar metamorphic conditions and mineral assemblages. These observations caution against generalised petrological interpretations on the basis of Y content, as it suggests Y concentrations in monazite are controlled by domainal equilibria. The results reveal a ~45 Myr interval between prograde metamorphism and retrograde melt crystallisation in the study area, emphasising the long-lived nature of heat flow in high-grade metamorphic terranes. Such long timescales of metamorphism would be assisted by the growth, retention and dominance of high-Th suprasolidus monazite, as observed in this study, contributing to the radiogenic heating budget of mid- to lower-crustal environments. Careful characterisation of monazite grains suggests that continuum-style U-Pb datasets can be decoded to provide insights into the duration of metamorphic processes.Natural Sciences and Engineering Research Council Visiting Fellowship Isaac Newton Trust Research Grant (RG74916

Report on the 1st SPARC Stratospheric Network for the Assessment of Predictability (SNAP). April 24-26 April 2013, Reading, UK

Stratospheric Network for the Assessment of Predictability (SNAP), 24-26 April 2013, Reading, UKThe first SPARC Stratospheric Network for the Assessment of Predictability (SPARC-SNAP) workshop was organized in the Department of Meteorology, University of Reading, UK, from 24 to 26 April 2013. This was a joint workshop with 3rd SPARC Dynamical Variability (SPARC-DynVar) (Manzini et al., this issue) workshop 22-24 April with the 24th April as a joint day. The joint workshop was well attended and had around 100 participants (http://www.met.reading.ac.uk/~pn904784/DynVar_SNAP_Workshop/participant.html) from 16 countries in Europe, Asia, Africa, Australia, North America, and South America (Participants figure). In the SNAP part of workshop (including the joint day) there were two keynote address, nine invited talks, six contributory talks and 24 posters.The authors are grateful to the Natural Environment Research Council and WCRP-SPARC for their financial support

Lipoprotein(a) and the Risk for Recurrent Atherosclerotic Cardiovascular Events Among Adults With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study

Rationale & Objective: Many adults with chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD) have high lipoprotein(a) levels. It is unclear whether high lipoprotein(a) levels confer an increased risk for recurrent ASCVD events in this population. We estimated the risk for recurrent ASCVD events associated with lipoprotein(a) in adults with CKD and prevalent ASCVD. Study Design: Observational cohort study. Setting & Participants: We included 1,439 adults with CKD and prevalent ASCVD not on dialysis enrolled in the Chronic Renal Insufficiency Cohort study between 2003 and 2008. Exposure: Baseline lipoprotein(a) mass concentration, measured using a latex-enhanced immunoturbidimetric assay. Outcomes: Recurrent ASCVD events (primary outcome), kidney failure, and death (exploratory outcomes) through 2019. Analytical Approach: We used Cox proportional-hazards regression models to estimate adjusted HR (aHRs) and 95% CIs. Results: Among participants included in the current analysis (mean age 61.6 years, median lipoprotein(a) 29.4 mg/dL [25th-75th percentiles 9.9-70.9 mg/dL]), 641 had a recurrent ASCVD event, 510 developed kidney failure, and 845 died over a median follow-up of 6.6 years. The aHR for ASCVD events associated with 1 standard deviation (SD) higher log-transformed lipoprotein(a) was 1.04 (95% CI, 0.95-1.15). In subgroup analyses, 1 SD higher log-lipoprotein(a) was associated with an increased risk for ASCVD events in participants without diabetes (aHR, 1.23; 95% CI, 1.02-1.48), but there was no evidence of an association among those with diabetes (aHR, 0.99; 95% CI, 0.88-1.10, P comparing aHRs = 0.031). The aHR associated with 1 SD higher log-lipoprotein(a) in the overall study population was 1.16 (95% CI, 1.04-1.28) for kidney failure and 1.02 (95% CI, 0.94-1.11) for death. Limitations: Lipoprotein(a) was not available in molar concentration. Conclusions: Lipoprotein(a) was not associated with the risk for recurrent ASCVD events in adults with CKD, although it was associated with a risk for kidney failure

Rhinovirus induction of fractalkine (CX3CL1) in airway and peripheral blood mononuclear cells in asthma

Rhinovirus infection is associated with the majority of asthma exacerbations. The role of fractalkine in anti-viral (type 1) and pathogenic (type 2) responses to rhinovirus infection in allergic asthma is unknown. To determine whether (1) fractalkine is produced in airway cells and in peripheral blood leucocytes, (2) rhinovirus infection increases production of fractalkine and (3) levels of fractalkine differ in asthmatic compared to non-asthmatic subjects. Fractalkine protein and mRNA levels were measured in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) from non-asthmatic controls (n = 15) and mild allergic asthmatic (n = 15) subjects. Protein levels of fractalkine were also measured in macrophages polarised ex vivo to give M1 (type 1) and M2 (type 2) macrophages and in BAL fluid obtained from mild (n = 11) and moderate (n = 14) allergic asthmatic and non-asthmatic control (n = 10) subjects pre and post in vivo rhinovirus infection. BAL cells produced significantly greater levels of fractalkine than PBMCs. Rhinovirus infection increased production of fractalkine by BAL cells from non-asthmatic controls (P<0.01) and in M1-polarised macrophages (P<0.05), but not in BAL cells from mild asthmatics or in M2 polarised macrophages. Rhinovirus induced fractalkine in PBMCs from asthmatic (P<0.001) and healthy control subjects (P<0.05). Trends towards induction of fractalkine in moderate asthmatic subjects during in vivo rhinovirus infection failed to reach statistical significance. Fractalkine may be involved in both immunopathological and anti-viral immune responses to rhinovirus infection. Further investigation into how fractalkine is regulated across different cell types and into the effect of stimulation including rhinovirus infection is warranted to better understand the precise role of this unique dual adhesion factor and chemokine in immune cell recruitment

Examining the predictability of the Stratospheric Sudden Warming of January 2013 using multiple NWP systems

The first multi-model study to estimate the predictability of a boreal Sudden Stratospheric Warming (SSW) is performed using five NWP systems. During the 2012-2013 boreal winter, anomalous upward propagating planetary wave activity was observed towards the end of December, which followed by a rapid deceleration of the westerly circulation around 2 January 2013, and on 7 January 2013 the zonal mean zonal wind at 60°N and 10 hPa reversed to easterly. This stratospheric dynamical activity was followed by an equatorward shift of the tropospheric jet stream and by a high pressure anomaly over the North Atlantic, which resulted in severe cold conditions in the UK and Northern Europe. In most of the five models, the SSW event was predicted 10 days in advance. However, only some ensemble members in most of the models predicted weakening of westerly wind when the models were initialized 15 days in advance of the SSW. Further dynamical analysis of the SSW shows that this event was characterized by the anomalous planetary wave-1 amplification followed by the anomalous wave-2 amplification in the stratosphere, which resulted in a split vortex occurring between 6 January 2013 and 8 January 2013. The models have some success in reproducing wave-1 activity when initialized 15 days in advance, they but generally failed to produce the wave-2 activity during the final days of the event. Detailed analysis shows that models have reasonably good skill in forecasting tropospheric blocking features that stimulate wave-2 amplification in the troposphere, but they have limited skill in reproducing wave-2 amplification in the stratosphere

Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain

Protocol for a parallel group, two-arm, superiority cluster randomised trial to evaluate a community-level complementary-food safety and hygiene and nutrition intervention in Mali:the MaaCiwara study (version 1.3; 10 November 2022)

BACKGROUND: Diarrhoeal disease remains a significant cause of morbidity and mortality among the under-fives in many low- and middle-income countries. Changes to food safety practices and feeding methods around the weaning period, alongside improved nutrition, may significantly reduce the risk of disease and improve development for infants. We describe a protocol for a cluster randomised trial to evaluate the effectiveness of a multi-faceted community-based educational intervention that aims to improve food safety and hygiene behaviours and enhance child nutrition. METHODS: We describe a mixed-methods, parallel group, two-arm, superiority cluster randomised controlled trial with baseline measures. One hundred twenty clusters comprising small urban and rural communities will be recruited in equal numbers and randomly allocated in a 1:1 ratio to either treatment or control arms. The community intervention will be focussed around an ideal mother concept involving all community members during campaign days with dramatic arts and pledging, and follow-up home visits. Participants will be mother–child dyads (27 per cluster period) with children aged 6 to 36 months. Data collection will comprise a day of observation and interviews with each participating mother–child pair and will take place at baseline and 4 and 15 months post-intervention. The primary analysis will estimate the effectiveness of the intervention on changes to complementary-food safety and preparation behaviours, food and water contamination, and diarrhoea. Secondary outcomes include maternal autonomy, enteric infection, nutrition, child anthropometry, and development scores. A additional structural equation analysis will be conducted to examine the causal relationships between the different outcomes. Qualitative and health economic analyses including process evaluation will be done. CONCLUSIONS: The trial will provide evidence on the effectiveness of community-based behavioural change interventions designed to reduce the burden of diarrhoeal disease in the under-fives and how effectiveness varies across different contexts. TRIAL REGISTRATION: ISRCTN14390796. Registration date December 13, 2021 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06984-5

IL-33-dependent Type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo

Rationale: Rhinoviruses are the major cause of asthma exacerbations; however, its underlying mechanisms are poorly understood. We hypothesized that the epithelial cell–derived cytokine IL-33 plays a central role in exacerbation pathogenesis through augmentation of type 2 inflammation. Objectives: To assess whether rhinovirus induces a type 2 inflammatory response in asthma in vivo and to define a role for IL-33 in this pathway. Methods: We used a human experimental model of rhinovirus infection and novel airway sampling techniques to measure IL-4, IL-5, IL-13, and IL-33 levels in the asthmatic and healthy airways during a rhinovirus infection. Additionally, we cultured human T cells and type 2 innate lymphoid cells (ILC2s) with the supernatants of rhinovirusinfected bronchial epithelial cells (BECs) to assess type 2 cytokine production in the presence or absence of IL-33 receptor blockade. Measurements and Main Results: IL-4, IL-5, IL-13, and IL-33 are all induced by rhinovirus in the asthmatic airway in vivo and relate to exacerbation severity. Further, induction of IL-33 correlates with viral load and IL-5 and IL-13 levels. Rhinovirus infection of human primary BECs induced IL-33, and culture of human T cells and ILC2s with supernatants of rhinovirus-infected BECs strongly induced type 2 cytokines. This induction was entirely dependent on IL-33. Conclusions: IL-33 and type 2 cytokines are induced during a rhinovirus-induced asthma exacerbation in vivo. Virus-induced IL-33 and IL-33–responsive T cells and ILC2s are key mechanistic links between viral infection and exacerbation of asthma. IL-33 inhibition is a novel therapeutic approach for asthma exacerbation

Effects on childhood infections of promoting safe and hygienic complementary-food handling practices through a community-based programme: A cluster randomised controlled trial in a rural area of The Gambia.

BACKGROUND: The Gambia has high rates of under-5 mortality from diarrhoea and pneumonia, peaking during complementary-feeding age. Community-based interventions may reduce complementary-food contamination and disease rates. METHODS AND FINDINGS: A public health intervention using critical control points and motivational drivers, delivered February-April 2015 in The Gambia, was evaluated in a cluster randomised controlled trial at 6- and 32-month follow-up in September-October 2015 and October-December 2017, respectively. After consent for trial participation and baseline data were collected, 30 villages (clusters) were randomly assigned to intervention or control, stratified by population size and geography. The intervention included a community-wide campaign on days 1, 2, 17, and 25, a reminder visit at 5 months, plus informal community-volunteer home visits. It promoted 5 key complementary-food and 1 key drinking-water safety and hygiene behaviours through performing arts, public meetings, and certifications delivered by a team from local health and village structures to all villagers who attended the activities, to which mothers of 6- to 24-month-old children were specifically invited. Control villages received a 1-day campaign on domestic-garden water use. The background characteristics of mother and clusters (villages) were balanced between the trial arms. Outcomes were measured at 6 and 32 months in a random sample of 21-26 mothers per cluster. There were no intervention or research team visits to villages between 6 and 32 months. The primary outcome was a composite outcome of the number of times key complementary-food behaviours were observed as a proportion of the number of opportunities to perform the behaviours during the observation period at 6 months. Secondary outcomes included the rate of each recommended behaviour; microbiological growth from complementary food and drinking water (6 months only); and reported acute respiratory infections, diarrhoea, and diarrhoea hospitalisation. Analysis was by intention-to-treat analysis adjusted by clustering. (Registration: PACTR201410000859336). We found that 394/571 (69%) of mothers with complementary-feeding children in the intervention villages were actively involved in the campaign. No villages withdrew, and there were no changes in the implementation of the intervention. The intervention improved behaviour adoption significantly. For the primary outcome, the rate was 662/4,351(incidence rate [IR] = 0.15) in control villages versus 2,861/4,378 (IR = 0.65) in intervention villages (adjusted incidence rate ratio [aIRR] = 4.44, 95% CI 3.62-5.44, p < 0.001), and at 32 months the aIRR was 1.17 (95% CI 1.07-1.29, p = 0.001). Secondary health outcomes also improved with the intervention: (1) mother-reported diarrhoea at 6 months, with adjusted relative risk (aRR) = 0.39 (95% CI 0.32-0.48, p < 0.001), and at 32 months, with aRR = 0.68 (95% CI 0.48-0.96, p = 0.027); (2) mother-reported diarrhoea hospitalisation at 6 months, with aRR = 0.35 (95% CI 0.19-0.66, p = 0.001), and at 32 months, with aRR = 0.38 (95% CI 0.18-0.80, p = 0.011); and (3) mother-reported acute respiratory tract infections at 6 months, with aRR = 0.67 (95% CI 0.53-0.86, p = 0.001), though at 32 months improvement was not significant (p = 0.200). No adverse events were reported. The main limitations were that only medium to small rural villages were involved. Obtaining laboratory cultures from food at 32 months was not possible, and no stool microorganisms were investigated. CONCLUSIONS: We found that low-cost and culturally embedded behaviour change interventions were acceptable to communities and led to short- and long-term improvements in complementary-food safety and hygiene practices, and reported diarrhoea and acute respiratory tract infections. TRIAL REGISTRATION: The trial was registered on the 17th October 2014 with the Pan African Clinical Trial Registry in South Africa with number (PACTR201410000859336) and 32-month follow-up as an amendment to the trial