A temperate former West Antarctic ice sheet suggested by an extensive zone of bed channels

Several recent studies predict that the West Antarctic Ice Sheet will become increasingly unstable under warmer conditions. Insights on such change can be assisted through investigations of the subglacial landscape, which contains imprints of former ice-sheet behavior. Here, we present radio-echo sounding data and satellite imagery revealing a series of ancient large sub-parallel subglacial bed channels preserved in the region between the Möller and Foundation Ice Streams, West Antarctica. We suggest that these newly recognized channels were formed by significant meltwater routed along the icesheet bed. The volume of water required is likely substantial and can most easily be explained by water generated at the ice surface. The Greenland Ice Sheet today exemplifies how significant seasonal surface melt can be transferred to the bed via englacial routing. For West Antarctica, the Pliocene (2.6–5.3 Ma) represents the most recent sustained period when temperatures could have been high enough to generate surface melt comparable to that of present-day Greenland. We propose, therefore, that a temperate ice sheet covered this location during Pliocene warm periods

Divergence between genes but limited allelic polymorphism in two MHC class II A genes in Leach’s storm-petrels Oceanodroma leucorhoa

The major histocompatibility complex (MHC) is critical to host-pathogen interactions. Class II MHC is a heterodimer, with α and β subunits encoded by different genes. The peptide-binding groove is formed by the first domain of both subunits (α1 and β1), but studies of class II variation or natural selection focus primarily on the β subunit and II B genes. We explored MHC II A in Leach’s storm-petrel, a seabird with two expressed, polymorphic II B genes. We found two II A genes, Ocle-DAA and Ocle-DBA, in contrast to the single II A gene in chicken and duck. In exon 2 which encodes the α1 domain, the storm-petrel II A genes differed strongly from each other but showed little within-gene polymorphism in 30 individuals: just one Ocle-DAA allele, and three Ocle-DBA alleles differing from each other by single non-synonymous substitutions. In a comparable sample, the two II B genes had nine markedly diverged alleles each. Differences between the α1 domains of Ocle-DAA and Ocle-DBA showed signatures of positive selection, but mainly at non-peptide-binding site (PBS) positions. In contrast, positive selection within and between the II B genes corresponded to putative PBS codons. Phylogenetic analysis of the conserved α2 domain did not reveal deep or well-supported lineages of II A genes in birds, in contrast to the pronounced differentiation of DQA, DPA, and DRA isotypes in mammals. This uncertain homology complicates efforts to compare levels of functional variation and modes of evolution of II A genes across taxa

Vitamin A, systemic T-cells, and the eye: Focus on degenerative retinal disease

The first discovered vitamin, vitamin A, exists in a range of forms, primarily retinoids and provitamin carotenoids. The bioactive forms of vitamin A, retinol and retinoic acid, have many critical functions in body systems including the eye and immune system. Vitamin A deficiency is associated with dysfunctional immunity, and presents clinically as a characteristic ocular syndrome, xerophthalmia. The immune functions of vitamin A extend to the gut, where microbiome interactions and nutritional retinoids and carotenoids contribute to the balance of T cell differentiation, thereby determining immune status and contributing to inflammatory disease around the whole body. In the eye, degenerative conditions affecting the retina and uvea are influenced by vitamin A. Stargardt’s disease (STGD1; MIM 248200) is characterised by bisretinoid deposits such as lipofuscin, produced by retinal photoreceptors as they use and recycle a vitamin A-derived chromophore. Age-related macular degeneration features comparable retinal deposits, such as drusen featuring lipofuscin accumulation; and is characterised by parainflammatory processes. We hypothesise that local parainflammatory processes secondary to lipofuscin deposition in the retina are mediated by T cells interacting with dietary vitamin A derivatives and the gut microbiome, and outline the current evidence for this. No cures exist for Stargardt’s or age-related macular degeneration, but many vitamin A-based therapeutic approaches have been or are being trialled. The relationship between vitamin A’s functions in systemic immunology and the eye could be further exploited, and further research may seek to leverage the interactions of the gut-eye immunological axis

Imaging in Vascular Access

This review examines four imaging modalities; ultrasound (US), digital subtraction angiography (DSA), magnetic resonance imaging (MRI) and computed tomography (CT), that have common or potential applications in vascular access (VA). The four modalities are reviewed under their primary uses, techniques, advantages and disadvantages, and future directions that are specific to VA. Currently, US is the most commonly used modality in VA because it is cheaper (relative to other modalities), accessible, non-ionising, and does not require the use of contrast agents. DSA is predominantly only performed when an intervention is indicated. MRI is limited by its cost and the time required for image acquisition that mainly confines it to the realm of research where high resolution is required. CT’s short acquisition times and high resolution make it useful as a problem-solving tool in complex cases, although accessibility can be an issue. All four imaging modalities have advantages and disadvantages that limit their use in this particular patient cohort. Current imaging in VA comprises an integrated approach with each modality providing particular uses dependent on their capabilities. MRI and CT, which currently have limited use, may have increasingly important future roles in complex cases where detailed analysis is required

Natural Resistance-Associated Macrophage Protein Is a Cellular Receptor for Sindbis Virus in Both Insect and Mammalian Hosts

SummaryAlphaviruses, including several emerging human pathogens, are a large family of mosquito-borne viruses with Sindbis virus being a prototypical member of the genus. The host factor requirements and receptors for entry of this class of viruses remain obscure. Using a Drosophila system, we identified the divalent metal ion transporter natural resistance-associated macrophage protein (NRAMP) as a host cell surface molecule required for Sindbis virus binding and entry into Drosophila cells. Consequently, flies mutant for dNRAMP were protected from virus infection. NRAMP2, the ubiquitously expressed vertebrate homolog, mediated binding and infection of Sindbis virus into mammalian cells, and murine cells deficient for NRAMP2 were nonpermissive to infection. Alphavirus glycoprotein chimeras demonstrated that the requirement for NRAMP2 is at the level of Sindbis virus entry. Given the conserved structure of alphavirus glycoproteins, and the widespread use of transporters for viral entry, other alphaviruses may use conserved multipass membrane proteins for infection

Associations of Air Pollution and Pediatric Asthma in Cleveland, Ohio

Air pollution has been associated with poor health outcomes and continues to be a risk factor for respiratory health in children. While higher particulate matter (PM) levels are associated with increased frequency of symptoms, lower lung function, and increase airway inflammation from asthma, the precise composition of the particles that are more highly associated with poor health outcomes or healthcare utilization are not fully elucidated. PM is measured quantifiably by current air pollution monitoring systems. To better determine sources of PM and speciation of such sources, a particulate matter (PM) source apportionment study, the Cleveland Multiple Air Pollutant Study (CMAPS), was conducted in Cleveland, Ohio, in 2009–2010, which allowed more refined assessment of associations with health outcomes. This article presents an evaluation of short-term (daily) and long-term associations between motor vehicle and industrial air pollution components and pediatric asthma emergency department (ED) visits by evaluating two sets of air quality data with healthcare utilization for pediatric asthma. Exposure estimates were developed using land use regression models for long-term exposures for nitrogen dioxide (NO2) and coarse (i.e., with aerodynamic diameters between 2.5 and 10 μm) particulate matter (PM) and the US EPA Positive Matrix Factorization receptor model for short-term exposures to fine (μm) and coarse PM components. Exposure metrics from these two approaches were used in asthma ED visit prevalence and time series analyses to investigate seasonal-averaged short- and long-term impacts of both motor vehicles and industry emissions. Increased pediatric asthma ED visits were found for LUR coarse PM and NO2 estimates, which were primarily contributed by motor vehicles. Consistent, statistically significant associations with pediatric asthma visits were observed, with short-term exposures to components of fine and coarse iron PM associated with steel production. Our study is the first to combine spatial and time series analysis of ED visits for asthma using the same periods and shows that PM related to motor vehicle emissions and iron/steel production are associated with increased pediatric asthma visits

The effectiveness of community-based coordinating interventions in dementia care:a meta-analysis and subgroup analysis of intervention components

Abstract Background Interventions aiming to coordinate services for the community-based dementia population vary in components, organisation and implementation. In this review we aimed to evaluate the effectiveness of community-based care coordinating interventions on health outcomes and investigate whether specific components of interventions influence their effects. Methods We searched four databases from inception to April 2017: Medline, The Cochrane Library, EMBASE and PsycINFO. This was aided by a search of four grey literature databases, and backward and forward citation tracking of included papers. Title and abstract screening was followed by a full text screen by two independent reviewers, and quality was assessed using the CASP appraisal tool. We then conducted meta-analyses and subgroup analyses. Results A total of 14 randomised controlled trials (RCTs) involving 10,372 participants were included in the review. Altogether we carried out 12 meta-analyses and 19 subgroup analyses. Meta-analyses found coordinating interventions showed a statistically significant improvement in both patient behaviour measured using the Neuropsychiatric Inventory (NPI) (mean difference (MD) = −9.5; 95% confidence interval (CI): −18.1 to −1.0; p = 0.03; number of studies (n) = 4; I2 = 88%) and caregiver burden (standardised mean difference (SMD) = −0.54; 95% CI: -1.01 to −0.07; p = 0.02; n = 5, I2 = 92%) compared to the control group. Subgroup analyses found interventions using a case manager with a nursing background showed a greater positive effect on caregiver quality of life than those that used case managers from other professional backgrounds (SMD = 0.94 versus 0.03, respectively; p < 0.001). Interventions that did not provide supervision for the case managers showed greater effectiveness for reducing the percentage of patients that are institutionalised compared to those that provided supervision (odds ratio (OR) = 0.27 versus 0.96 respectively; p = 0.02). There was little evidence of effects on other outcomes, or that other intervention components modify the intervention effects. Conclusion Results show that coordinating interventions in dementia care has a positive impact on some outcomes, namely patient behaviour and caregiver burden, but the evidence is inconsistent and results were not strong enough to draw definitive conclusions on general effectiveness. With the rising prevalence of dementia, effective complex interventions will be necessary to provide high quality and effective care for patients, and facilitate collaboration of health, social and third sector services