The VLT-FLAMES survey of massive stars: observations in the Galactic clusters NGC3293, NGC4755 and NGC6611

We introduce a new survey of massive stars in the Galaxy and the Magellanic Clouds using the Fibre Large Array Multi-Element Spectrograph (FLAMES) instrument at the Very Large Telescope (VLT). Here we present observations of 269 Galactic stars with the FLAMES-Giraffe Spectrograph (R ~ 25,000), in fields centered on the open clusters NGC 3293, NGC 4755 and NGC 6611. These data are supplemented by a further 50 targets observed with the Fibre-Fed Extended Range Optical Spectrograph (FEROS, R = 48,000). Following a description of our scientific motivations and target selection criteria, the data reduction methods are described; of critical importance the FLAMES reduction pipeline is found to yield spectra that are in excellent agreement with less automated methods. Spectral classifications and radial velocity measurements are presented for each star, with particular attention paid to morphological peculiarities and evidence of binarity. These observations represent a significant increase in the known spectral content of NGC 3293 and NGC 4755, and will serve as standards against which our subsequent FLAMES observations in the Magellanic Clouds will be compared.Comment: 26 pages, 9 figures (reduced size). Accepted for publication in A&A. A copy with full res. figures is available from http://www.ing.iac.es/~cje/flames_mw.ps.gz. Minor changes following correction of proof

A functional riboSNitch in the 3' untranslated region of FKBP5 alters MicroRNA-320a binding efficiency and mediates vulnerability to chronic post-traumatic pain

Previous studies have shown that common variants of the gene coding for FK506-binding protein 51 (FKBP5), a critical regulator of glucocorticoid sensitivity, affect vulnerability to stress-related disorders. In a previous report, FKBP5 rs1360780 was identified as a functional variant because of its effect on gene methylation. Here we report evidence for a novel functional FKBP5 allele, rs3800373. This study assessed the association between rs3800373 and post-traumatic chronic pain in 1607 women and men from two ethnically diverse human cohorts. The molecular mechanism through which rs3800373 affects adverse outcomes was established via in silico, in vivo, and in vitro analyses. The rs3800373 minor allele predicted worse adverse outcomes after trauma exposure, such that individuals with the minor (risk) allele developed more severe post-traumatic chronic musculoskeletal pain. Among these individuals, peritraumatic circulating FKBP5 expression levels increased as cortisol and glucocorticoid receptor (NR3C1) mRNA levels increased, consistent with increased glucocorticoid resistance. Bioinformatic, in vitro, and mutational analyses indicate that the rs3800373 minor allele reduces the binding of a stress-and pain-associated microRNA, miR-320a, to FKBP5 via altering the FKBP5 mRNA 3'UTR secondary structure (i.e., is a riboSNitch). This results in relatively greater FKBP5 translation, unchecked by miR-320a. Overall, these results identify an important gene–miRNA interaction influencing chronic pain risk in vulnerable individuals and suggest that exogenous methods to achieve targeted reduction in poststress FKBP5 mRNA expression may constitute useful therapeutic strategies

Microflares and the Statistics of X-ray Flares

This review surveys the statistics of solar X-ray flares, emphasising the new views that RHESSI has given us of the weaker events (the microflares). The new data reveal that these microflares strongly resemble more energetic events in most respects; they occur solely within active regions and exhibit high-temperature/nonthermal emissions in approximately the same proportion as major events. We discuss the distributions of flare parameters (e.g., peak flux) and how these parameters correlate, for instance via the Neupert effect. We also highlight the systematic biases involved in intercomparing data representing many decades of event magnitude. The intermittency of the flare/microflare occurrence, both in space and in time, argues that these discrete events do not explain general coronal heating, either in active regions or in the quiet Sun.Comment: To be published in Space Science Reviews (2011

Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Integrated screening validates primary axes of specialisation in plants

Standardised procedures have been used to measure 67 traits in 43 common plants of the British flora. This paper provides an interpretation of the most consistent patterns in the resulting matrix by means of correlation, ordination and classification analyses. Only a weak coupling was observed between attributes of the regenerative and established phases of the life history. However, within each phase, attributes were strongly aggregated into sets and a high proportion of the variation between species coincided with a single axis. Attributes of the established phase displayed remarkably consistent trends, with a strong 'Axis I' being identified by three different multivariate methods. There was a marked correlation between foliar concentrations of N, P, K, Ca and Mg, high concentrations of which coincided with the capacity for rapid growth in productive conditions and an inability to sustain yield under limiting supplies of nutrients. A diverse array of other traits, less immediately involving mineral nutrients, were also entrained in Axis I; these included life history, root and shoot foraging, the morphology, longevity, tensile strength and palatability of leaves, and the decomposition rate of leaf litter. This pattern occurred in both monocotyledons and dicotyledons and appeared to reflect a tradeoff between attributes conferring an ability for high rates of resource acquisition in productive habitats and those responsible for retention of resource capital in unproductive conditions. The second axis of variation evident in the established phase was related to phylogeny and distinguished between monocotyledons and dicotyledons on the basis of a diverse set of traits including genome size, cell size, root and shoot foraging characteristics and vascular tissues. A third axis was detected in which ephemerals and perennials were separated by differences in attributes such as breeding system, leaf decomposition rate and a set of traits reflecting the small stature of many short-lived plants. In the regenerative phase, the leading axis was clearly related to the widely recognized tradeoff between seed size and seed number and was consistent with current understanding of seed banks, and with modern theories explaining species coexistence in terms of complementary responses to temporal and spatial variation in vegetation gap dynamics. The data provide strong evidence of functional integration between evolutionary specializations in root and shoot and support Donald's unified theory of competitive ability. The data are not consistent with theories of functional types based upon evolutionary tradeoffs in allocation between root and shoot. We suggest that the evidence assembled here and elsewhere in the current literature points to the existence of primary functional types, including those recognized by Ramenskii and Grime. These functional types can be reconciled with the individuality of plant ecologies in the field and provide an effective basis for interpretation and prediction at various scales from the plant community to regional floras. There are particular opportunities for prediction of successional trajectories, the role of herbivores in vegetation succession and the response of vegetation to eutrophication and extreme climatic events. It is also suggested that aspects of this investigation may provide a Darwinian underpinning for Odum's theory of ecosystem maturation