Effectiveness and cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children (The BEEP trial): protocol for a randomised controlled trial.

BACKGROUND: Atopic eczema (AE) is a common skin problem that impairs quality of life and is associated with the development of other atopic diseases including asthma, food allergy and allergic rhinitis. AE treatment is a significant cost burden for health care providers. The purpose of the trial is to investigate whether daily application of emollients for the first year of life can prevent AE developing in high-risk infants (first-degree relative with asthma, AE or allergic rhinitis). METHODS: This is a protocol for a pragmatic, two-arm, randomised controlled, multicentre trial. Up to 1400 term infants at high risk of developing AE will be recruited through the community, primary and secondary care in England. Participating families will be randomised in a 1:1 ratio to receive general infant skin-care advice, or general skin-care advice plus emollients with advice to apply daily to the infant for the first year of life. Families will not be blinded to treatment allocation. The primary outcome will be a blinded assessment of AE at 24 months of age using the UK Working Party Diagnostic Criteria for Atopic Eczema. Secondary outcomes are other definitions of AE, time to AE onset, severity of AE (EASI and POEM), presence of other allergic diseases including food allergy, asthma and hay fever, allergic sensitisation, quality of life, cost-effectiveness and safety of the emollients. Subgroup analyses are planned for the primary outcome according to filaggrin genotype and the number of first-degree relatives with AE and other atopic diseases. Families will be followed up by online and postal questionnaire at 3, 6, 12 and 18 months with a face-to-face visit at 24 months. Long-term follow-up until 60 months will be via annual questionnaires. DISCUSSION: This trial will demonstrate whether skin-barrier enhancement through daily emollient for the first year of life can prevent AE from developing in high-risk infants. If effective, this simple and cheap intervention has the potential to result in significant cost savings for health care providers throughout the world by preventing AE and possibly other associated allergic diseases. TRIAL REGISTRATION: ISRCTN registry; ID: ISRCTN21528841 . Registered on 25 July 2014

Evidence for a novel Carbohydrate Binding Module (CBM) of Tannerella forsythia NanH sialidase, key to interactions at the host-pathogen interface

Bacterial sialidases cleave terminal sialic acid from a variety of host glycoproteins, and contribute to survival and growth of many human-dwelling bacterial species, including various pathogens.Tannerella forsythia, an oral, Gram-negative, fastidious anaerobe, is a key organism in periodontal disease, and possesses a dedicated sialic acid utilisation and scavenging (nan) operon, including NanH sialidase. Here, we describe biochemical characterisation of recombinant NanH, including its action on host-relevant sialoglycans such as sialyl Lewis A and sialyl Lewis X (SLeA/X), and on human cell-attached sialic acids directly, uncovering that it is a highly active broad specificity sialidase. Furthermore, theN-terminal domain of NanH was hypothesised and proven to be capable of binding to a range of sialoglycans and non-sialylated derivatives withKdin the micromolar range, as determined by steady-state tryptophan fluorescence spectroscopy, but it has no catalytic activity in isolation from the active site. We consider this domain to represent the founding member of a novel subfamily of Carbohydrate Binding Module (CBM), involved in glycosidase-ligand binding. In addition, we created a catalytically inactive version of the NanH enzyme (FRIP→YMAP) that retained its ability to bind sialic acid-containing ligands and revealed for the first time that binding activity of a CBM is enhanced by association with the catalytic domain. Finally, we investigated the importance of Lewis-type sialoglycans onT. forsythia-host interactions, showing that nanomolar amounts of SLeA/Xwere capable of reducing invasion of oral epithelial cells byT. forsythiasuggesting that these are key ligands for bacterial-cellular interactions during periodontal disease

Approaches to quantitative reconstruction of woody vegetation in managed woodlands from pollen records

There has been increasing interest in developing quantitative methods for reconstructing the dynamics of cultural landscapes over the last 15 years. This paper adds to this literature by using various approaches to reconstruct the vegetation of two woodlands subject to rotational coppicing (the periodic cutting of broadleaved trees and shrubs for wood products). Pollen deposition at ground level was determined at both sites using ‘Tauber’ traps placed near to the centre of 14 compartments of differing age in the coppice rotation. For the main woody taxa, Relative Pollen Productivity (RPP) estimates were derived using linear regression for pollen influx data and Extended R-value analysis for percentage data. The vegetation around three ponds was reconstructed by applying four methods (inverting the two RPP estimate approaches, the modern analogue technique and correction for pollen productivity using the linear regression estimated RPP values) to pollen data obtained from the uppermost sample of sediment from the ponds. To determine whether these methods gave better estimates of the vegetation composition than the original pollen proportions, the results were compared with the surveyed vegetation around each pond using the Bray–Curtis Index. Linear regression of pollen influx produced RPP values which are comparable with previous European studies, whilst for some taxa the Extended R-value analysis produced estimates which are orders of magnitude different both from values derived from the linear regression and previous work. No single approach performed equally well at reconstructing the vegetation around the ponds, and at two of the three locations the uncorrected pollen proportions were most similar to the surveyed vegetation.We conclude that applying quantitative reconstruction methods to individual small sites is, currently, not likely to be useful in complex cultural landscapes. In the context of coppiced woodland, deficiencies in our understanding of pollen taphonomy and the impact of the practice on pollen production first need to be rectified, and we identify strategies to address this situation

Characterization of Porphyromonas gingivalis sialidase and disruption of its role in host–pathogen interactions

Key to onset and progression of periodontitis is a complex relationship between oral bacteria and the host. The organisms most associated with severe periodontitis are the periodontal pathogens of the red complex: Tannerella forsythia , Treponema denticola and Porphyromonas gingivalis . These organisms express sialidases, which cleave sialic acid from host glycoproteins, and contribute to disease through various mechanisms. Here, we expressed and purified recombinant P. gingivalis sialidase SiaPG (PG_0352) and characterized its activity on a number of substrates, including host sialoglycoproteins and highlighting the inability to cleave diacetylated sialic acids – a phenomenon overcome by the NanS sialate-esterase from T. forsythia . Indeed SiaPG required NanS to maximize sialic acid harvesting from heavily O-acetylated substrates such as bovine salivary mucin, hinting at the possibility of interspecies cooperation in sialic acid release from host sources by these members of the oral microbiota. Activity of SiaPG and P. gingivalis was inhibited using the commercially available chemotherapeutic zanamivir, indicating its potential as a virulence inhibitor, which also inhibited sialic acid release from mucin, and was capable of inhibiting biofilm formation of P. gingivalis on oral glycoprotein sources. Zanamivir also inhibited attachment and invasion of oral epithelial cells by P. gingivalis and other periodontal pathogens, both in monospecies but also in multispecies infection experiments, indicating potential to suppress host–pathogen interactions of a mixed microbial community. This study broadens our understanding of the multifarious roles of bacterial sialidases in virulence, and indicates that their inhibition with chemotherapeutics could be a promising strategy for periodontitis therapy

Pollen signals of ground flora in managed woodlands

This paper explores the vegetation signals contained in the non-arboreal pollen and spore (NAPS) components of pollen assemblages from Tauber traps placed in woodlands subject to rotational cutting (coppicing) in lowland England. Sets of three Tauber traps were placed in compartments of different ages at multiple locations within each woodland for 1 year, and pollen assemblages recorded along with a vegetation survey using a modified pin-frame method in an area of 10 m radius around each trap array. Cluster analysis suggests that, as expected, the ground layer vegetation broadly reflects the different environmental conditions in the three woods, with the main subdivisions within woods apparently driven by changes in ground cover between the early and late stages of the coppice cycle. Non-arboreal pollen and spores (NAPS) assemblages group according to woodland of origin, with subdivisions which relate to pollen abundance but lack a simple relationship with years since cutting. Indices of Association between NAPS records and plant presence in the area around each array were calculated using presence–absence data for multiple distances of vegetation survey. All values tend towards an asymptote, which is interpreted as implying an effective source area for the single taxon presence–absence indicator values of ground flora taxa in coppiced woodlands on the order of a 10 m radius. Only four taxa, Poaceae, Ranunculus acris-type, Cyperaceae, and Scilla-type, have an Index of Association (A) greater than 0.5, implying that the presence of pollen can be interpreted in terms of the local presence of the relevant plant taxon with some confidence. Estimates of Pollen Productivity relative to Poaceae are presented for five taxa: Apiaceae, Asteraceae (Cardueae), Cyperaceae, Mercurialis perennis, and Scilla-type. Years since cutting does affect the ground vegetation and NAPS assemblage trapped in these woods, but that the effect is more clearly seen at an assemblage level in the vegetation than in the pollen assemblages. The interpretative significance of NAPS taxa does not seem to be in providing information about the local conditions around the sampling point, but in reflecting the ground flora of the wider woodland

Drawing lines at the sand: evidence for functional vs. visual reef boundaries in temperate Marine Protected Areas.

Marine Protected Areas (MPAs) can either protect all seabed habitats within them or discrete features. If discrete features within the MPA are to be protected humans have to know where the boundaries are. In Lyme Bay, SW England a MPA excluded towed demersal fishing gear from 206 km(2) to protect rocky reef habitats and the associated species. The site comprised a mosaic of sedimentary and reef habitats and so 'non reef' habitat also benefited from the MPA. Following 3 years protection, video data showed that sessile Reef Associated Species (RAS) had colonised sedimentary habitat indicating that 'reef' was present. This suggested that the functional extent of the reef was potentially greater than its visual boundary. Feature based MPA management may not adequately protect targeted features, whereas site based management allows for shifting baselines and will be more effective at delivering ecosystem goods and services

Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review