Red giants in the outer halo of the elliptical galaxy NGC 5128 / Centaurus A

We used VIMOS on VLT to perform $V$ and $I$ band imaging of the outermost halo of NGC 5128 / Centaurus A ($(m-M)_0=27.91\pm0.08$), 65 kpc from the galaxy's center and along the major axis. The stellar population has been resolved to $I_0 \approx 27$ with a $50\%$ completeness limit of $I_0 = 24.7$, well below the tip of the red-giant branch (TRGB), which is seen at $I_0 \approx 23.9$. The surface density of NGC 5128 halo stars in our fields was sufficiently low that dim, unresolved background galaxies were a major contaminant in the source counts. We isolated a clean sample of red-giant-branch (RGB) stars extending to $\approx 0.8$ mag below the TRGB through conservative magnitude and color cuts, to remove the (predominantly blue) unresolved background galaxies. We derived stellar metallicities from colors of the stars via isochrones and measured the density falloff of the halo as a function of metallicity by combining our observations with HST imaging taken of NGC 5128 halo fields closer to the galaxy center. We found both metal-rich and metal-poor stellar populations and found that the falloff of the two follows the same de Vaucouleurs' law profiles from $\approx 8$ kpc out to $\approx$ 70 kpc. The metallicity distribution function (MDF) and the density falloff agree with the results of two recent studies of similar outermost halo fields in NGC 5128. We found no evidence of a "transition" in the radial profile of the halo, in which the metal-rich halo density would drop rapidly, leaving the underlying metal-poor halo to dominate by default out to greater radial extent, as has been seen in the outer halo of two other large galaxies. If NGC 5128 has such a transition, it must lie at larger galactocentric distances.Comment: Accepted for publication in A&A. 11 pages, including 14 figures and 1 tabl

Action 3:30R: Results of a cluster randomised feasibility study of a revised teaching assistant-led extracurricular physical activity intervention for 8 to 10 year olds

Many children are not sufficiently physically active. We conducted a cluster-randomised feasibility trial of a revised after-school physical activity (PA) programme delivered by trained teaching assistants (TAs) to assess the potential evidence of promise for increasing moderate-to-vigorous physical activity (MVPA). Participants (n = 335) aged 8–10 years were recruited from 12 primary schools in South West England. Six schools were randomised to receive the intervention and six acted as non-intervention controls. In intervention schools, TAs were trained to deliver an after-school programme for 15 weeks. The difference in mean accelerometer-assessed MVPA between intervention and control schools was assessed at follow-up (T1). The cost of programme delivery was estimated. Two schools did not deliver the intervention, meaning four intervention and six control schools were analysed at T1. There was no evidence for a difference in MVPA at T1 between intervention and control groups. Programme delivery cost was estimated at £2.06 per pupil per session. Existing provision in the 12 schools cost £5.91 per pupil per session. Action 3:30 was feasible to deliver and considerably cheaper than existing after-school provision. No difference in weekday MVPA was observed at T1 between the two groups, thus progression to a full trial is not warranted

Acanthaster planci, across the Hawaiian Archipelago and Johnston Atoll

The population structure of marine species is variable along the Hawaiian Archipelago; thus, it is important to understand dispersal and recruitment patterns for economically and ecologically important taxa to inform Ecosystem-based Management. Connectivity of the coral-eating crown-of-thorns sea star, Acanthaster planci, was examined from Johnston Atoll and 12 locations across the Hawaiian Archipelago. Sequences of mitochondrial DNA from 383 individuals were analyzed to infer patterns of gene flow among the Northwestern Hawaiian Islands (NWHIs), the main Hawaiian Islands, and Johnston Atoll. Population samples were genetically similar across the Hawaiian Archipelago with the exception of the west side of the Big Island of Hawaii, which was significantly differentiated from the majority of Hawaiian samples (pairwise Φ ST = 0.0607-0.1068, P < .05). Although differentiated, Hawai'i West shares haplotypes with every other site across the Hawaiian Archipelago. Johnston Atoll was genetically distinct from every location (pairwise Φ ST = 0.064-0.13, P < .05) except French Frigate Shoals (Φ ST = 0.03, P = .10), supporting connectivity between the central NWHIs and Johnston Atoll. Taken together with the lack of geographic population structure and haplotypes shared among all populations, these results indicate widespread larval dispersal with few restrictions to gene flow along the archipelago

Widespread Dispersal of the Crown-of-Thorns Sea Star, Acanthaster planci

The population structure of marine species is variable along the Hawaiian Archipelago; thus, it is important to understand dispersal and recruitment patterns for economically and ecologically important taxa to inform Ecosystem-based Management. Connectivity of the coral-eating crown-of-thorns sea star, Acanthaster planci, was examined from Johnston Atoll and 12 locations across the Hawaiian Archipelago. Sequences of mitochondrial DNA from 383 individuals were analyzed to infer patterns of gene flow among the Northwestern Hawaiian Islands (NWHIs), the main Hawaiian Islands, and Johnston Atoll. Population samples were genetically similar across the Hawaiian Archipelago with the exception of the west side of the Big Island of Hawaii, which was significantly differentiated from the majority of Hawaiian samples (pairwise ΦST=0.0607-0.1068, <.05). Although differentiated, Hawai`i West shares haplotypes with every other site across the Hawaiian Archipelago. Johnston Atoll was genetically distinct from every location (pairwise ΦST=0.064-0.13, <.05) except French Frigate Shoals (ΦST=0.03, =.10), supporting connectivity between the central NWHIs and Johnston Atoll. Taken together with the lack of geographic population structure and haplotypes shared among all populations, these results indicate widespread larval dispersal with few restrictions to gene flow along the archipelago

Analysis of candidate genes for macular telangiectasia type 2

Purpose: To find the gene(s) responsible for macular telangiectasia type 2 (MacTel) by a candidate-gene screening approach.Methods: Candidate genes were selected based on the following criteria: those known to cause or be associated with diseases with phenotypes similar to MacTel, genes with known function in the retinal vasculature or macular pigment transport, genes that emerged from expression microarray data from mouse models designed to mimic MacTel phenotype characteristics, and genes expressed in the retina that are also related to diabetes or hypertension, which have increased prevalence in MacTel patients. Probands from eight families with at least two affected individuals were screened by direct sequencing of 27 candidate genes. Identified nonsynonymous variants were analyzed to determine whether they cosegregate with the disease in families. Allele frequencies were determined by TaqMan analysis of the large MacTel and control cohorts.Results: We identified 23 nonsynonymous variants in 27 candidate genes in at least one proband. Of these, eight were known single nucleotide polymorphisms (SNPs) with allele frequencies of >0.05; these variants were excluded from further analyses. Three previously unidentified missense variants, three missense variants with reported disease association, and five rare variants were analyzed for segregation and/or allele frequencies. No variant fulfilled the criteria of being causal for MacTel. A missense mutation, p.Pro33Ser in frizzled homolog (Drosophila) 4 (FZD4), previously suggested as a disease-causing variant in familial exudative vitreoretinopathy, was determined to be a rare benign polymorphism.Conclusions: We have ruled out the exons and flanking intronic regions in 27 candidate genes as harboring causal mutations for MacTel

Engineering hemoglobin to enable homogenous PEGylation without modifying protein functionality

In order to infuse hemoglobin into the vasculature as an oxygen therapeutic or blood substitute, it is necessary to increase the size of the molecule to enhance vascular retention. This aim can be achieved by PEGylation. However, using non-specific conjugation methods creates heterogenous mixtures and alters protein function. Site-specific PEGylation at the naturally reactive thiol on human hemoglobin (βCys93) alters hemoglobin oxygen binding affinity and increases its autooxidation rate. In order to avoid this issue, new reactive thiol residues were therefore engineered at sites distant to the heme group and the α/β dimer/dimer interface. The two mutants were βCys93Ala/αAla19Cys and βCys93Ala/βAla13Cys. Gel electrophoresis, size exclusion chromatography and mass spectrometry revealed efficient PEGylation at both αAla19Cys and βAla13Cys, with over 80% of the thiols PEGylated in the case of αAla19Cys. For both mutants there was no significant effect on the oxygen affinity or the cooperativity of oxygen binding. PEGylation at αAla19Cys had the additional benefit of decreasing the rates of autoxidation and heme release, properties that have been considered contributory factors to the adverse clinical side effects exhibited by previous hemoglobin based oxygen carriers. PEGylation at αAla19Cys may therefore be a useful component of future clinical products

Non-randomised feasibility study testing a primary care intervention to promote engagement in an online health community for adults with troublesome asthma: protocol

Introduction: In the UK, approximately 4.3 million adults have asthma, with one-third experiencing poor asthma control, affecting their quality of life, and increasing their healthcare use. Interventions promoting emotional/behavioural self-management can improve asthma control and reduce comorbidities and mortality. Integration of online peer support into primary care services to foster self-management is a novel strategy. We aim to co-design and evaluate an intervention for primary care clinicians to promote engagement with an asthma online health community (OHC). Our protocol describes a ‘survey leading to a trial’ design as part of a mixed-methods, non-randomised feasibility study to test the feasibility and acceptability of the intervention. Methods and analysis: Adults on the asthma registers of six London general practices (~3000 patients) will be invited to an online survey, via text messages. The survey will collect data on attitudes towards seeking online peer support, asthma control, anxiety, depression, quality of life, information on the network of people providing support with asthma and demographics. Regression analyses of the survey data will identify correlates/predictors of attitudes/receptiveness towards online peer support. Patients with troublesome asthma, who (in the survey) expressed interest in online peer support, will be invited to receive the intervention, aiming to reach a recruitment target of 50 patients. Intervention will involve a one-off, face-to-face consultation with a practice clinician to introduce online peer support, sign patients up to an established asthma OHC, and encourage OHC engagement. Outcome measures will be collected at baseline and 3 months post intervention and analysed with primary care and OHC engagement data. Recruitment, intervention uptake, retention, collection of outcomes, and OHC engagement will be assessed. Interviews with clinicians and patients will explore experiences of the intervention. Ethics and dissemination: Ethical approval was obtained from a National Health Service Research Ethics Committee (reference: 22/NE/0182). Written consent will be obtained before intervention receipt and interview participation. Findings will be shared via dissemination to general practices, conference presentations and peer-reviewed publications. Trial registration number: NCT05829265

The XMM Cluster Survey: X-ray analysis methodology

The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters using all publicly available data in the XMM-Newton Science Archive. Its main aims are to measure cosmological parameters and trace the evolution of X-ray scaling relations. In this paper we describe the data processing methodology applied to the 5,776 XMM observations used to construct the current XCS source catalogue. A total of 3,675 > 4-sigma cluster candidates with > 50 background-subtracted X-ray counts are extracted from a total non-overlapping area suitable for cluster searching of 410 deg^2. Of these, 993 candidates are detected with > 300 background-subtracted X-ray photon counts, and we demonstrate that robust temperature measurements can be obtained down to this count limit. We describe in detail the automated pipelines used to perform the spectral and surface brightness fitting for these candidates, as well as to estimate redshifts from the X-ray data alone. A total of 587 (122) X-ray temperatures to a typical accuracy of < 40 (< 10) per cent have been measured to date. We also present the methodology adopted for determining the selection function of the survey, and show that the extended source detection algorithm is robust to a range of cluster morphologies by inserting mock clusters derived from hydrodynamical simulations into real XMM images. These tests show that the simple isothermal beta-profiles is sufficient to capture the essential details of the cluster population detected in the archival XMM observations. The redshift follow-up of the XCS cluster sample is presented in a companion paper, together with a first data release of 503 optically-confirmed clusters.Comment: MNRAS accepted, 45 pages, 38 figures. Our companion paper describing our optical analysis methodology and presenting a first set of confirmed clusters has now been submitted to MNRA

The Molecular Biogeography of the Indo-Pacific: Testing Hypotheses With Multispecies Genetic Patterns

Aim: To test hypothesized biogeographic partitions of the tropical Indo-Pacific Ocean with phylogeographic data from 56 taxa, and to evaluate the strength and nature of barriers emerging from this test. \u3eLocation: The Indo-Pacific Ocean. Time Period: Pliocene through the Holocene. Major Taxa Studied: Fifty-six marine species. Methods: We tested eight biogeographic hypotheses for partitioning of the Indo-Pacific using a novel modification to analysis of molecular variance. Putative barriers to gene flow emerging from this analysis were evaluated for pairwise ΦST, and these ΦST distributions were compared to distributions from randomized datasets and simple coalescent simulations of vicariance arising from the Last Glacial Maximum. We then weighed the relative contribution of distance versus environmental or geographic barriers to pairwise ΦST with a distance-based redundancy analysis (dbRDA). Results: We observed a diversity of outcomes, although the majority of species fit a few broad biogeographic regions. Repeated coalescent simulation of a simple vicariance model yielded a wide distribution of pairwise ΦST that was very similar to empirical distributions observed across five putative barriers to gene flow. Three of these barriers had median ΦST that were significantly larger than random expectation. Only 21 of 52 species analysed with dbRDA rejected the null model. Among these, 15 had overwater distance as a significant predictor of pairwise ΦST, while 11 were significant for geographic or environmental barriers other than distance. Main Conclusions: Although there is support for three previously described barriers, phylogeographic discordance in the Indo-Pacific Ocean indicates incongruity between processes shaping the distributions of diversity at the species and population levels. Among the many possible causes of this incongruity, genetic drift provides the most compelling explanation: given massive effective population sizes of Indo-Pacific species, even hard vicariance for tens of thousands of years can yield ΦST values that range from 0 to nearly 0.5