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

The bioaccumulation testing strategy for manufactured nanomaterials: physico-chemical triggers and read across from earthworms in a meta-analysis

Little is known about the bioaccumulation potential of manufactured nanomaterials (MNs). For traditional chemicals, the Organisation for Economic Co-operation and Development (OECD) Test Guideline (TG) 305, bioaccumulation in fish is often used. However, for MNs, there are no approved processes to trigger or waive this test, or consider alternatives to vertebrate animals. The aim of the present study was to conduct a meta-analysis of existing data sets on particle properties and bioaccumulation in earthworms to understand what particle metrics could be used as a trigger for bioaccumulation testing. An apparent steady state tissue concentration of metal from MNs exposure in the earthworm (Eisenia fetida) was evident following exposures to Ag nanoparticles (NPs), CuO NPs and CdTe quantum dots (QDs). This allowed the derivation of nano bioaccumulation factors (nBAFs), calculated using soil and earthworm tissue metal concentrations. A prediction equation using all the particle metrics correlated with BAFs was possible. Similarly, nano biomagnification factors (nBMFs) were calculated in the rainbow trout (Oncorhynchus mykiss) tissue, relative to the concentration of total metals in the fish diet. Pearson's correlations were found to be significant, with p < 0.05 for nBMFs for the liver, mid intestine, hind intestine and kidney relative to the earthworm tissue nBAFs. Together these data indicate that bioaccumulation measurements in earthworms for metallic MNs could be predictive of those values in fish, and that there is scope to predict the bioaccumulation potential of MNs with confidence from a few simple particle metrics

Emollients for prevention of atopic dermatitis; 5‐year findings from the BEEP randomised trial

Background The effectiveness of emollients for preventing atopic dermatitis/eczema is controversial. The Barrier Enhancement for Eczema Prevention trial evaluated the effects of daily emollients during the first year of life on atopic dermatitis and atopic conditions to age 5 years. Methods 1394 term infants with a family history of atopic disease were randomized (1:1) to daily emollient plus standard skin-care advice (693 emollient group) or standard skin-care advice alone (701 controls). Long-term follow-up at ages 3, 4 and 5 years was via parental questionnaires. Main outcomes were parental report of a clinical diagnosis of atopic dermatitis and food allergy. Results Parents reported more frequent moisturizer application in the emollient group through to 5 years. A clinical diagnosis of atopic dermatitis between 12 and 60 months was reported for 188/608 (31%) in the emollient group and 178/631 (28%) in the control group (adjusted relative risk 1.10, 95% confidence interval 0.93 to 1.30). Although more parents in the emollient group reported food reactions in the previous year at 3 and 4 years, cumulative incidence of doctor-diagnosed food allergy by 5 years was similar between groups (92/609 [15%] emollients and 87/632 [14%] controls, adjusted relative risk 1.11, 95% confidence interval 0.84 to 1.45). Findings were similar for cumulative incidence of asthma and hay fever. Conclusions Daily emollient application during the first year of life does not prevent atopic dermatitis, food allergy, asthma or hay fever

Epigenetic control of nuclear architecture

The cell nucleus is a highly structured compartment where nuclear components are thought to localize in non-random positions. Correct positioning of large chromatin domains may have a direct impact on the localization of other nuclear components, and can therefore influence the global functionality of the nuclear compartment. DNA methylation of cytosine residues in CpG dinucleotides is a prominent epigenetic modification of the chromatin fiber. DNA methylation, in conjunction with the biochemical modification pattern of histone tails, is known to lock chromatin in a close and transcriptionally inactive conformation. The relationship between DNA methylation and large-scale organization of nuclear architecture, however, is poorly understood. Here we briefly summarize present concepts of nuclear architecture and current data supporting a link between DNA methylation and the maintenance of large-scale nuclear organization

Insights into IgM-mediated complement activation based on in situ structures of IgM-C1-C4b

Antigen binding by serum Ig-M (IgM) protects against microbial infections and helps to prevent autoimmunity, but causes life-threatening diseases when mistargeted. How antigen-bound IgM activates complement-immune responses remains unclear. We present cryoelectron tomography structures of IgM, C1, and C4b complexes formed on antigen-bearing lipid membranes by normal human serum at 4 degrees C. The IgM-C1-C4b complexes revealed C4b product release as the temperature-limiting step in complement activation. Both IgM hexamers and pentamers adopted hexagonal, dome-shaped structures with Fab pairs, dimerized by hinge domains, bound to surface antigens that support a platform of Fc regions. C1 binds IgM through widely spread C1q-collagen helices, with C1r proteases pointing outward and C1s bending downward and interacting with surface-attached C4b, which further interacts with the adjacent IgM-Fab(2) and globular C1q-recognition unit. Based on these data, we present mechanistic models for antibody-mediated, C1q-transmitted activation of C1 and for C4b deposition, while further conformational rearrangements are required to form C3 convertases.Microscopic imaging and technolog

Varying the Pre-discharge Lithium Wall Coatings to Alter the Characteristics of the ELM-free H-mode Pedestal in NSTX

A previous experiment in the National Spherical Torus Experiment (NSTX) showed pre-discharge lithium deposition gradually suppresed edge-localized modes (ELMs) and had nearly continuous relationships with reduced recycling and transport. In this paper, additional data filled gaps in the earlier experiment, and demonstrates that recycling, confinement, and pedestal structure continued to improve with additional lithium, even after ELMs were completely suppressed. New analysis shows that toroidal rotation and ion temperature also increased continuously with additional lithium. Besides its evolution with additional lithium, we also characterize the time evolution of the ELM-free H-mode pedestal as average density rose and impurities accumulated. We find that the pedestal structure, divertor heat flux and Dalpha profiles, and inferred recycling coefficient did not change significantly, at least until radiative losses become dominant. This suggests that the low-recycling properties of lithium were not significantly degraded over the duration of the discharge

Caracterização citogenética em Schlumbergera truncata (Haworth) Moran e Schlumbergera &times; buckleyi (T. Moore) Tjaden (Cactaceae) Cytogenetic characterization of Schlumbergera truncata (Haworth) Moran and Schlumbergera &times; buckleyi (T. Moore) Tjaden (Cactaceae)

O número cromossômico diplóide de Schlumbergera truncata e Schlumbergera x buckleyi, de indivíduos com diferentes tipos de coloração de pétalas, foi determinado usando-se pontas de raízes. A utilização de 8-hidroxiquinoleína 0,003 M à 36 &deg;C por 3 horas possibilitou melhor separação cromossômica. Técnica de bandeamento C e de coloração Giemsa permitiram o estudo cariológico dessas espécies. O híbrido Schlumbergera &times; buckleyi (rósea) apresenta 2n = 22 cromossomos com fórmula cariotípica 16 M + 6 SM. Schlumbergera truncata, apresentando pétalas nas cores vermelha, branca e pink, possui 2n = 22 cromossomos, formulação cariotípica idêntica à de Schlumbergera &times; buckleyi, enquanto a planta com flores de coloração amarelada mostrou 2n = 34 cromossomos. A classificação cromossômica foi baseada no índice centromérico. Nas plantas que apresentam coloração vermelha, branca, pink e rósea nas pétalas, o melhor período de obtenção de metáfases corresponde ao período de florescimento. Schlumbergera truncata com flores amareladas apresenta dois picos anuais de divisão mitótica. Esses resultados dão suporte à um melhor entendimento da biologia no gênero Schlumbergera e auxiliam na classificação taxonômica nos casos onde apenas as características fenotípicas não são suficientemente confiáveis para a classificação das plantas no mesmo táxon.<br>The diploid chromosome number of Schlumbergera truncata and Schlumbergera &times; buckleyi, in individuals with different types of petal color, was determined using root tips. The use of 8-hydroxyquinolein 0.003 M at 36 ºC provided better chromosome separation. C-banding technique and Giemsa coloration allowed the karyological study of these species. Schlumbergera &times; buckleyi hybrid (light pink) species has 2n = 22 chromosomes with karyotype formula 16M + 6SM. Schlumbergera truncata with red, white, and pink petals and 2n = 22 chromosomes has karyotype formula identical to Schlumbergera &times; buckleyi, while the plant with yellowish flowers has 2n = 34 chromosomes. Chromosome classification was based on the centromeric index. In plants with white, red, pink and light pink petal color, the best time to obtain metaphases is during flowering. Schlumbergera truncata with yellowish flowers has two annual peaks of mitotic division. These results give us a better understanding of the biology of the genus Schlumbergera and aid in taxonomic classification where phenotypic characteristics alone are not reliable enough to classify plants of the same taxon

The Relationships Between ELM Suppression, Pedestal Profiles, and Lithium Wall Coatings in NSTX

Recently in the National Spherical Torus Experiment (NSTX), increasing lithium wall coatings suppressed edge localized modes (ELMs), gradually but not quite monotonically. This work details profile and stability analysis as ELMs disappeared throughout the lithium scan. While the quantity of lithium deposited between discharges did not uniquely determine the presence of ELMs, profile analysis demonstrated that lithium was correlated to wider density and pressure pedestals with peak gradients farther from the separatrix. Moreover, the ELMy and ELM-free discharges were cleanly separated by their density and pedestal widths and peak gradient locations. Ultimately, ELMs were only suppressed when lithium caused the density pedestal to widen and shift inward. These changes in the density gradient were directly reflected in the pressure gradient and calculated bootstrap current. This supports the theory that ELMs in NSTX are caused by peeling and/or ballooning modes, as kink/peeling modes are stabilized when the edge current and pressure gradient shift away from the separatrix. Edge stability analysis using ELITE corroborated this picture, as reconstructed equilibria from ELM-free discharges were generally farther from their kink/peeling stability boundaries than ELMy discharges. We conclude that density profile control provided by lithium is the key first step to ELM suppression in NST