Atopic dermatitis (AD) has become a significant public health problem because of increasing prevalence, together with increasing evidence that it may progress to other allergic phenotypes. While it ...is now acknowledged that AD commonly precedes other allergic diseases, a link termed ‘the atopic march’, debate continues as to whether this represents a causal relationship. An alternative hypothesis is that this association may be related to confounding by familial factors or phenotypes that comanifest, such as early‐life wheeze and sensitization. However, there is increasing evidence from longitudinal studies suggesting that the association between AD and other allergies is independent of confounding by comanifest allergic phenotypes. The hypotheses on plausible biological mechanisms for the atopic march focus on defective skin barrier function and overexpression of inflammatory mediators released by the skin affected by AD (including thymic stromal lymphopoietin). Both human and animal studies have provided evidence supporting these potential biological mechanisms. Evidence from prevention trials is now critical to establishing a causal nature of the atopic march. An emerging area of research is investigation into environmental modifiers of the atopic march. Such information will assist in identifying secondary prevention strategies to arrest the atopic march. Despite much research into the aetiology of allergies, little progress has been made in identifying effective strategies to reduce the burden of allergic conditions. In this context, the atopic march remains a promising area of investigation.
Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and ...clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC.
The impact of early childhood traffic‐related air pollution (TRAP) exposure on development of asthma and allergies remains unclear. Birth cohort studies are the best available study design to answer ...this question, but the evidence from such studies has not been synthesized to date. We conducted a systematic review and meta‐analyses of published birth cohort studies to understand the association between early childhood TRAP exposure, and subsequent asthma, allergies and sensitization. Increased longitudinal childhood exposure to PM2.5 and black carbon was associated with increasing risk of subsequent asthma in childhood (PM2.5: OR 1.14, 95%CI 1.00 to 1.30 per 2 μg/m3 and black carbon: OR 1.20, 95%CI 1.05 to 1.38 per 1 × 10−5 m−1). Also, early childhood exposure to TRAP was associated with development of asthma across childhood up to 12 years of age. The magnitude of these associations increased with age, and the pattern was prominent for PM2.5. Increasing exposure to PM2.5 was associated with sensitization to both aero‐ and food allergens. There was some evidence that TRAP was associated with eczema and hay fever. In summary, exposure to TRAP was related to asthma and allergic diseases. However, the substantial variability across studies warrants long‐term birth cohort studies with regular repeated follow‐ups to confirm these findings.
A new coupled general circulation climate model developed at the Met Office’s Hadley Centre is presented, and aspects of its performance in climate simulations run for the Intergovernmental Panel on ...Climate Change Fourth Assessment Report (IPCC AR4) documented with reference to previous models. The Hadley Centre Global Environmental Model version 1 (HadGEM1) is built around a new atmospheric dynamical core; uses higher resolution than the previous Hadley Centre model, HadCM3; and contains several improvements in its formulation including interactive atmospheric aerosols (sulphate, black carbon, biomass burning, and sea salt) plus their direct and indirect effects. The ocean component also has higher resolution and incorporates a sea ice component more advanced than HadCM3 in terms of both dynamics and thermodynamics. HadGEM1 thus permits experiments including some interactive processes not feasible with HadCM3. The simulation of present-day mean climate in HadGEM1 is significantly better overall in comparison to HadCM3, although some deficiencies exist in the simulation of tropical climate and El Niño variability. We quantify the overall improvement using a quasi-objective climate index encompassing a range of atmospheric, oceanic, and sea ice variables. It arises partly from higher resolution but also from greater fidelity in modeling dynamical and physical processes, for example, in the representation of clouds and sea ice. HadGEM1 has a similar effective climate sensitivity (2.8 K) to a CO₂ doubling as HadCM3 (3.1 K), although there are significant regional differences in their response patterns, especially in the Tropics. HadGEM1 is anticipated to be used as the basis both for higher-resolution and higher-complexity Earth System studies in the near future.
The rate of soil-transmitted helminth (STH) infection is estimated to be around 20% in Indonesia. Health promotion and health education are cost-effective strategies to supplement STH prevention and ...control programs. Existing studies suggest that quantitative tools for knowledge, attitudes and practices (KAP) are important to monitor effective community-based STH interventions. However, evidence is limited regarding the applicability of such tools. This study aims to identify the socio-demographic predictors for STH-related knowledge and practices and validate the quantitative tools in population use. A cross-sectional study design was conducted among residents of 16 villages in Central Java, Indonesia. Adult and child respondents were interviewed to assess general knowledge and practices in relation to STH. Two mixed effects models identified the significant factors in predicting knowledge and practice scores. The model predicted knowledge and practice scores were compared with the observed scores to validate the quantitative measurements developed in this study. Participants' socio-demographic variables were significant in predicting an individual's STH-related knowledge level and their hand washing and hygiene practices, taking into account household-level variability. Model validation results confirmed that the quantitative measurement tools were suitable for assessing STH associated knowledge and behaviour. The questionnaire developed in this study can be used to support school- and community-based health education interventions to maximize the effect of STH prevention and control programs.
In addition to projected increases in global mean sea level over the 21st century, model simulations suggest there will also be changes in the regional distribution of sea level relative to the ...global mean. There is a considerable spread in the projected patterns of these changes by current models, as shown by the recent Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment (AR4). This spread has not reduced from that given by the Third Assessment models. Comparison with projections by ensembles of models based on a single structure supports an earlier suggestion that models of similar formulation give more similar patterns of sea level change. Analysing an AR4 ensemble of model projections under a business-as-usual scenario shows that steric changes (associated with subsurface ocean density changes) largely dominate the sea level pattern changes. The relative importance of subsurface temperature or salinity changes in contributing to this differs from region to region and, to an extent, from model-to-model. In general, thermosteric changes give the spatial variations in the Southern Ocean, halosteric changes dominate in the Arctic and strong compensation between thermosteric and halosteric changes characterises the Atlantic. The magnitude of sea level and component changes in the Atlantic appear to be linked to the amount of Atlantic meridional overturning circulation (MOC) weakening. When the MOC weakening is substantial, the Atlantic thermosteric patterns of change arise from a dominant role of ocean advective heat flux changes.
The scattering treated here arises when elastic waves propagate within a heterogeneous medium defined by random spatial fluctuation of its elastic properties. Whereas classical analytical studies are ...based on lower-order scattering assumptions, numerical methods conversely present no such limitations by inherently incorporating multiple scattering. Until now, studies have typically been limited to two or one dimension, however, owing to computational constraints. This article seizes recent advances to realize a finite-element formulation that solves the three-dimensional elastodynamic scattering problem. The developed methodology enables the fundamental behaviour of scattering in terms of attenuation and dispersion to be studied. In particular, the example of elastic waves propagating within polycrystalline materials is adopted, using Voronoi tessellations to randomly generate representative models. The numerically observed scattering is compared against entirely independent but well-established analytical scattering theory. The quantitative agreement is found to be excellent across previously unvisited scattering regimes; it is believed that this is the first quantitative validation of its kind which provides significant support towards the existence of the transitional scattering regime and facilitates future deployment of numerical methods for these problems.
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