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Background: We previously reported that infants with Asian-born parents are 3 times more likely to have IgE-mediated food allergy than those with Australian-born parents. It is unknown whether this translates to the increased risk of other allergic diseases later in childhood and whether ancestry interacts with other risk factors for allergic disease development., Objective: To compare prevalence and risk factors for allergic rhinitis, asthma, and aeroallergen sensitization at age 6 between children with East Asian-born and Caucasian-born parents., Methods: A total of 5276 1-year-old infants were recruited into a population-based longitudinal study of allergy. A total of 4455 children participated in age 6 follow-up (84.4%), including 3015 with Caucasian-born parents and 415 with East Asian-born parents. Children underwent skin prick tests to aeroallergens and questionnaires captured data on asthma, eczema, and allergic rhinitis., Results: Compared with children with Caucasian-born parents, children of East Asian-born parents had more allergic rhinitis (19.9% [95% confidence interval (CI) 14.9-26] vs 9.3% [95% CI 8-10.8], P < .001) and aeroallergen sensitization (64.3% [95% CI 57.5-70.5] vs 34.4% [95% CI 32.2-36.7], P < .001) at age 6. Asthma was similar in both groups (9.1% [95% CI 6.2-13.2] vs 11.7% [95% CI 10.4-13.1]), P = .21. Children with IgE-mediated food allergy and eczema in infancy were 3 times more likely to have asthma and 2 times more likely to have allergic rhinitis at age 6, irrespective of ancestry., Conclusions: Children of East Asian ancestry born in Australia have a higher burden of most allergic diseases in the first 6 years of life, whereas asthma may follow a different pattern. IgE-mediated food allergy and eczema at age 1 increase the risk of asthma and allergic rhinitis irrespective of ancestry., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction : Food allergy currently affects up to 10% of infants. Identification and implementation of effective food allergy prevention strategies is thus imperative. Areas covered : We focus on five food allergy risk factors/prevention strategies which have been or are currently being tested in randomized controlled trials: (1) timely introduction of allergenic foods into the infant diet; (2) maternal diet and consumption of allergenic foods during pregnancy and breastfeeding; (3) infant skin barrier and the role of moisturizers in early life; (4) infant Vitamin D levels and the role of Vitamin D supplementation; and (5) microbial exposure in early life. Expert commentary : Earlier introduction of allergenic foods, particularly peanut, in the infant diet has been shown to reduce food allergy. Novel intervention strategies, including infant vitamin D supplementation, maternal diet modifications, and moisturizing infants to improve skin barrier, are currently being tested in large-scale clinical trials. As results of these trials become available, we hope strategies that are both efficacious and cost-effective will be revealed and their implementation in the population, along with the timely introduction of allergenic foods, will reduce the burden of food allergy in future generations.

Background: Longitudinal population-based data regarding tree nut allergy are limited., Objectives: We sought to determine the population prevalence of tree nut allergy at age 6 years and explore the relationship between egg and peanut allergy at age 1 year and development of tree nut allergy at age 6 years., Methods: A population-based sample of 5276 children was recruited at age 1 year and followed up at age 6 years. At age 1 year, allergies to egg and peanut were determined by means of oral food challenge, and parents reported their child's history of reaction to tree nuts. Challenge-confirmed tree nut allergy was assessed at age 6 years., Results: At age 1 year, the prevalence of parent-reported tree nut allergy was 0.1% (95% CI, 0.04% to 0.2%). Only 18.5% of infants had consumed tree nuts in the first year of life. At age 6 years, challenge-confirmed tree nut allergy prevalence was 3.3% (95% CI, 2.8% to 4.0%), with cashew the most common (2.7%; 95% CI, 2.2% to 3.3%). Of children with peanut allergy only at age 1 year, 27% (95% CI, 16.1% to 39.7%) had tree nut allergy at age 6 years compared with 14% (95% CI, 10.4% to 17.9%) of those with egg allergy only and 37% (95% CI, 27.2% to 47.4%) of those with both peanut and egg allergy., Conclusions: Tree nut allergy is uncommon in the first year of life, likely because of limited tree nut consumption. At age 6 years, tree nut allergy prevalence is similar to peanut allergy prevalence. More than a third of children with both peanut and egg allergy in infancy have tree nut allergy at age 6 years. Understanding how to prevent tree nut allergy should be an urgent priority for future research., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Adolescence is well recognized as a period of increased risk for severe and fatal food-induced anaphylaxis. Current Australian adrenaline autoinjector (AAI) prescription guidelines therefore suggest that consideration be given to AAI prescription in all adolescents with a food allergy. To date, however, few studies have assessed the AAI carriage behavior of adolescents prescribed AAI devices., Objective: To determine the carriage behavior of prescribed AAI devices in a population-based sample of young Australian adolescents., Methods: Students aged 10 to 14 years (and their parents) from randomly selected schools in metropolitan Melbourne completed self-administered questionnaires regarding the history and management of food allergy, including prescription and carriage of AAI device in different domains of school and social life., Results: A total of 9816 students completed the questionnaire (46% response): 620 students were assessed to have likely IgE-mediated food allergy and 234 (38%) of these had been prescribed an AAI. Most students (93%; 95% CI, 89%-96%) who were prescribed AAIs reported that they provided their AAI and anaphylaxis action plan to their school. Adherence to AAI carriage in other domains of social life was poor, with 49% (95% CI, 42%-56%) never carrying their AAI in 1 or more locations. Carriage of the AAI device was particularly poor when students were independent of parental supervision: 32% (95% CI, 25%-39%) never carried it when they were by themselves, 28% (95% CI, 22%-36%) never carried it while out with friends, and 36% (95% CI, 30%-43%) never carried their AAI to sporting activities., Conclusions: Carriage of AAI devices is suboptimal in young adolescents prescribed AAIs, particularly when young adolescents are independent of parental supervision., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Calcification is a prevalent disease in most fully developed countries and is predominantly observed in heart valves and nearby vasculature. Calcification of either tissue leads to deterioration and, ultimately, failure causing poor quality of life and decreased overall life expectancy in patients. In valves, calcification presents as Calcific Aortic Valve Disease (CAVD), in which the aortic valve becomes stenotic when calcific nodules form within the leaflets. The initiation and progression of these calcific nodules is strongly influenced by the varied mechanical forces on the valve. In turn, the addition of calcific nodules creates localized disturbances in the tissue biomechanics, which affects extracellular matrix (ECM) production and cellular activation. In vasculature, atherosclerosis is the most common occurrence of calcification. Atherosclerosis exhibits as calcific plaque formation that forms in juxtaposition to areas of low blood shear stresses. Research in these two manifestations of calcification remain separated, although many similarities persist. Both diseases show that the endothelial layer and its regulation of nitric oxide is crucial to calcification progression. Further, there are similarities between vascular smooth muscle cells and valvular interstitial cells in terms of their roles in ECM overproduction. This review summarizes valvular and vascular tissue in terms of their basic anatomy, their cellular and ECM components and mechanical forces. Calcification is then examined in both tissues in terms of disease prediction, progression, and treatment. Highlighting the similarities and differences between these areas will help target further research toward disease treatment.

Vitamin D is critical to children's skeletal development and health. Despite this, the factors which determine vitamin D concentrations during infancy remain incompletely understood. This article reviews the literature assessing the factors which can affect vitamin D status in infancy, including antenatal and postnatal vitamin D supplementation. Observational data supports that dietary intake of vitamin D, UV exposure, and geographic factors contribute significantly to infants' vitamin D status, but the relationship is unclear regarding genetic variation, ethnicity, and maternal vitamin D status. Randomised controlled trials have compared higher versus lower doses of infant vitamin D supplementation, but no studies have compared infant vitamin D supplementation to placebo and eliminated external sources of vitamin D to fully quantify its effect on vitamin D status. Knowledge gaps remain regarding the factors associated with optimal vitamin D concentrations in infants-including key factors such as ethnicity and genetic variation-and further studies are needed., Competing Interests: The authors declare no conflict of interest.

This review highlights research and policy advances in food allergy that were published in 2017 in the Journal and beyond. In 2017, many important studies on the treatment of food allergy were published, bringing us ever closer to a standardized treatment for food allergy. Other important advancements included research into other management strategies, including thresholds for avoidance, management of food allergies in schools, and development of new guidelines for prevention of food allergy. There were several important epidemiologic studies helping us understand the phenotypes of allergic disease, and new hypotheses were proposed for how best to prevent food allergy. Finally, there was a welcome increased attention to non-IgE-mediated food allergies., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Peanut allergy is classically managed by food avoidance. Immunotherapy programs are available at some academic centers for selected patients reacting to small amounts of peanut during food challenge. We aimed to determine and compare reaction thresholds and prevalence of anaphylaxis during peanut oral challenges at multiple specialist allergy centers., Methods: A retrospective, international survey of anonymized case records from seven specialist pediatric allergy centers from the UK and Ireland, as well as the Australian HealthNuts study. Demographic information, allergy test results, reaction severity and threshold during open oral peanut challenges were collated and analyzed., Results: Of the 1634 children aged 1-18 years old included, 525 (32%) failed their peanut challenge. Twenty-eight percent reacted to 25 mg, while 38% only reacted after consuming 1 g or more of whole peanut. Anaphylaxis (55 [11%]) was 3 times more common in teenagers than younger children and the likelihood increased at all ages as children consuming more peanut at the challenge. Children who developed anaphylaxis to 25-200 mg of whole peanut were significantly older. Previous history of reaction did not predict reaction threshold or severity., Conclusions: More than a third of the children in this large international cohort tolerated the equivalent of one peanut in an oral challenge. Anaphylaxis, particularly to small amounts of peanut, was more common in older children. Tailored immunotherapy programs might be considered not only for children with low, but also higher reaction thresholds. Whether these programs could prevent heightened sensitivity and anaphylaxis to peanut with age also deserves further study., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Asian children born in Australia have higher rates of eczema and nut allergy than non-Asian children. However, it is not known whether this country of birth differential exists for other allergies or anaphylaxis risk., Objective: We investigated the influence of maternal and child's country of birth on the prevalence of parent-reported eczema, asthma, food allergy and being diagnosed by a doctor as being "at risk of anaphylaxis.", Methods: We assessed the relationship between mother and child country of birth and allergies using the 2010 School Entrant Health Questionnaire, completed for 57 005 5-year old children (85.8% response rate) in Victoria, Australia. Analyses were conducted using logistic regression with results presented as odds ratios (OR) with 95% confidence intervals (CIs)., Results: Children born in Australia to Asian-born mothers were more likely to have parent-reported food allergy (OR 2.33, 95%CI 1.96-2.77) and eczema (OR 2.04, 95%CI 1.73-2.41), but not more likely to have asthma (OR 0.87, 95% CI 0.74-1.02) than non-Asian children. By contrast, children born in Asia who subsequently migrated to Australia had a lower risk of food allergy (OR 0.33, 95%CI 0.20-0.55), eczema (OR 0.37, 95%CI 0.24-0.57) and asthma (OR 0.29, 95% CI 0.21-0.40). Patterns of anaphylaxis risk differed depending on the trigger. Compared with Australian-born non-Asian children, Australian-born Asian children were more likely to be diagnosed as being at risk of both food-induced and non-food-induced anaphylaxis. For children born in Asia, risk was lower for anaphylaxis to milk, peanut and tree nuts compared to non-Asian children, but higher for soy, wheat and non-food triggers., Conclusions and Clinical Relevance: Patterns of allergy/anaphylaxis risk and their triggers differed according to both ethnicity and country of birth, suggesting a gene-environment factor is in play. The difference in patterns for asthma compared with other atopic diseases is surprising and warrants further exploration., (© 2018 John Wiley & Sons Ltd.)

Hyaluronan (HA), a high molecular weight non-sulfated glycosaminoglycan, is an integral component of the extracellular matrix of developing and mature connective tissues including tendon. There are few published reports quantifying HA content during tendon growth and maturation, or detailing its effects on the mechanical properties of the tendon extracellular matrix. Therefore, the goal of the current study was to examine the role of HA synthesis during post-natal skeletal growth and maturation, and its influence on tendon structure and biomechanical function. For this purpose, the morphological, biochemical, and mechanical properties of Achilles tendons from wild type (WT) and hyaluronan synthase 1 and 3 deficient mouse strains (Has1 -/- (Has1KO), Has3 -/- (Has3KO), and Has1 -/- 3 -/- (Has1/3KO)) were determined at 4, 8, and 12 weeks of age. Overall, HAS-deficient mice did not show any marked differences from WT mice in Achilles tendon morphology or in the HA and chondroitin/dermatan sulfate (CS/DS) contents. However, HAS1-deficiency (in the single or Has1/3 double KO) impeded post-natal formation of the retrocalcaneal bursa, implicating HAS1 in regulating HA metabolism by cells lining the bursal cavity. Together, these data suggest that HA metabolism via HAS1 and HAS3 does not markedly influence the extracellular matrix structure or function of the tendon body, but plays a role in the formation/maintenance of peritendinous bursa. Additional studies are warranted to elucidate the relationship of HA and CS/DS metabolism to tendon healing and repair in vivo. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2622-2632, 2018., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Discrete subaortic stenosis (DSS) is a congenital heart disease that results in the formation of a fibro-membranous tissue, causing an increased pressure gradient in the left ventricular outflow tract (LVOT). While surgical resection of the membrane has shown some success in eliminating the obstruction, it poses significant risks associated with anesthesia, sternotomy, and heart bypass, and it remains associated with a high rate of recurrence. Although a genetic etiology had been initially proposed, the association between DSS and left ventricle (LV) geometrical abnormalities has provided more support to a hemodynamic etiology by which congenital or post-surgical LVOT geometric derangements could generate abnormal shear forces on the septal wall, triggering in turn a fibrotic response. Validating this hypothetical etiology and understanding the mechanobiological processes by which altered shear forces induce fibrosis in the LVOT are major knowledge gaps. This perspective paper describes the current state of knowledge of DSS, articulates the research needs to yield mechanistic insights into a significant pathologic process that is poorly understood, and proposes several strategies aimed at elucidating the potential mechanobiological synergies responsible for DSS pathogenesis. The proposed roadmap has the potential to improve DSS management by identifying early targets for prevention of the fibrotic lesion, and may also prove beneficial in other fibrotic cardiovascular diseases associated with altered flow.

The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Rationale: Childhood risk factors for long-term lung health often coexist and their specific patterns may affect subsequent lung function differently., Objectives: To identify childhood risk factor profiles and their influence on lung function and chronic obstructive pulmonary disease (COPD) in middle age, and potential pathways., Methods: Profiles of 11 childhood respiratory risk factors, documented at age 7, were identified in 8,352 participants from the Tasmanian Longitudinal Health Study using latent class analysis. We investigated associations between risk profiles and post-bronchodilator lung function and COPD at age 53, mediation by childhood lung function and adult asthma, and interaction with personal smoking., Results: Six risk profiles were identified: 1) unexposed or least exposed (49%); 2) parental smoking (21.5%); 3) allergy (10%); 4) frequent asthma, bronchitis (8.7%); 5) infrequent asthma, bronchitis (8.3%); and 6) frequent asthma, bronchitis, allergy (2.6%). Profile 6 was most strongly associated with lower forced expiratory volume in 1 second (FEV 1 ) (-261; 95% confidence interval, -373 to -148 ml); lower FEV 1 /forced vital capacity (FVC) (-3.4; -4.8 to -1.9%) and increased COPD risk (odds ratio, 4.9; 2.1 to 11.0) at age 53. The effect of profile 6 on COPD was largely mediated by adult active asthma (62.5%) and reduced childhood lung function (26.5%). Profiles 2 and 4 had smaller adverse effects than profile 6. Notably, the effects of profiles 2 and 6 were synergistically stronger for smokers., Conclusions: Profiles of childhood respiratory risk factors predict middle-age lung function levels and COPD risk. Specifically, children with frequent asthma attacks and allergies, especially if they also become adult smokers, are the most vulnerable group. Targeting active asthma in adulthood (i.e., a dominant mediator) and smoking (i.e., an effect modifier) may block causal pathways and lessen the effect of such established early-life exposures.

Background: Food allergy naturally resolves in a proportion of food-allergic children without intervention; however the underlying mechanisms governing the persistence or resolution of food allergy in childhood are not understood., Objectives: This study aimed to define the innate immune profiles associated with egg allergy at age 1 year, determine the phenotypic changes that occur with the development of natural tolerance in childhood, and explore the relationship between early life innate immune function and serum vitamin D., Methods: This study used longitudinally collected PBMC samples from a population-based cohort of challenge-confirmed egg-allergic infants with either persistent or transient egg allergy outcomes in childhood to phenotype and quantify the functional innate immune response associated with clinical phenotypes of egg allergy., Results: We show that infants with persistent egg allergy exhibit a unique innate immune signature, characterized by increased numbers of circulating monocytes and dendritic cells that produce more inflammatory cytokines both at baseline and following endotoxin exposure when compared with infants with transient egg allergy. Follow-up analysis revealed that this unique innate immune signature continues into childhood in those with persistent egg allergy and that increased serum vitamin D levels correlate with changes in innate immune profiles observed in children who developed natural tolerance to egg., Conclusions: Early life innate immune dysfunction may represent a key immunological driver and predictor of persistent food allergy in childhood. Serum vitamin D may play an immune-modulatory role in the development of natural tolerance., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Eczema is a common childhood ailment responsible for a considerable disease burden. Both timing of introduction to solid food and allergenic food are believed to be related to childhood eczema. Despite the growing body of evidence, the relationship between timing of any solid food introduction (allergenic and/or non-allergenic) and development of eczema has not previously been systematically reviewed., Methods: PubMed and EMBASE databases were searched using food and eczema terms. Two authors selected papers according to the inclusion criteria and extracted information on study characteristics and measures of association. Meta-analyses were performed after grouping studies according to the age and type of exposure., Results: A total of 17 papers met the inclusion criteria, reporting results from 16 study populations. Of these, 11 were cohort studies, 2 case-controls, 1 cross-sectional study and 2 randomized controlled trials. Limited meta-analyses were performed due to heterogeneity between studies. Timing of solid food introduction was not associated with eczema. One randomized controlled trial provided weak evidence of an association between early allergenic (around 4 months) food introduction and reduced risk of eczema., Conclusions: The available evidence is currently insufficient to determine whether the timing of introduction of any solid food influences the risk of eczema., (© 2018 John Wiley & Sons Ltd.)

Biomaterials for tissue engineering that recapitulate the mechanical response and biological function of native tissue are highly sought after to lessen the burden of damaged or diseased tissue. Poly(ethylene glycol) diacrylate (PEGDA) hydrogels are a popular candidate because of their favorable bioactive properties. However, their mechanical behavior is very dissimilar to that of biological tissue, which behaves in a mechanically anisotropic, nonlinear, and viscoelastic fashion. It has been previously shown that PEGDA hydrogels can be patterned in alternating linear strips of different stiffnesses to generate anisotropic behavior, but these constructs still have a linear stress-strain response. In this study, we imparted nonlinear mechanical properties to PEGDA hydrogels by fabricating composite hydrogel constructs consisting of a stiff sinusoidal reinforcement embedded into a softer base matrix. This was achieved by polymerizing low molecular weight (MW) PEGDA hydrogel precursor into a stiff sinusoidal shape and then polymerizing this construct into a high MW precursor. Samples were generated with different relative stiffness between the two components and a range of sinusoid periodicities to assess the tunability of the resulting stress-strain curve. Tensile testing indicates that the sinusoidal patterning gives rise to nonlinear stress-strain behavior. Varying the relative stiffness was shown to tune the slope of the linear region of the stress-strain curve, and varying periodicity was shown to affect the length of the toe region of this curve. We conclude that composite hydrogels with stiff sinusoidally-patterned reinforcements display mechanical properties more similar to those of biological tissue than uniform or linearly-patterned hydrogels., Statement of Significance: Hydrogel biomaterials are a popular candidate for engineering constructs that can mimic the properties of native tissue for disease modeling and tissue-engineering applications. Studies have shown that poly(ethylene) glycol diacrylate (PEGDA) hydrogels can be fabricated to display many biological aspects of native tissue. However, they are unable to recapitulate fundamental mechanical properties of such tissue, such as anisotropy and nonlinearity. Photolithographic techniques have been employed to generate anisotropic linear PEGDA hydrogels via patterned reinforcement. The present study indicates that such techniques can be modified to generate PEGDA constructs with a sinusoidal reinforcement that display a strongly nonlinear response to tensile loading. This work sets the stage for more intricate patterning for providing increased control over hydrogel mechanical response., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Lifetime lung function is related to quality of life and longevity. Over the lifespan, individuals follow different lung function trajectories. Identification of these trajectories, their determinants, and outcomes is important, but no study has done this beyond the fourth decade., Methods: We used six waves of the Tasmanian Longitudinal Health Study (TAHS) to model lung function trajectories measured at 7, 13, 18, 45, 50, and 53 years. We analysed pre-bronchodilator FEV 1 z-scores at the six timepoints using group-based trajectory modelling to identify distinct subgroups of individuals whose measurements followed a similar pattern over time. We related the trajectories identified to childhood factors and risk of chronic obstructive pulmonary disease (COPD) using logistic regression, and estimated population-attributable fractions of COPD., Findings: Of the 8583 participants in the original cohort, 2438 had at least two waves of lung function data at age 7 years and 53 years and comprised the study population. We identified six trajectories: early below average, accelerated decline (97 [4%] participants); persistently low (136 [6%] participants); early low, accelerated growth, normal decline (196 [8%] participants); persistently high (293 [12%] participants); below average (772 [32%] participants); and average (944 [39%] participants). The three trajectories early below average, accelerated decline; persistently low; and below average had increased risk of COPD at age 53 years compared with the average group (early below average, accelerated decline: odds ratio 35·0, 95% CI 19·5-64·0; persistently low: 9·5, 4·5-20·6; and below average: 3·7, 1·9-6·9). Early-life predictors of the three trajectories included childhood asthma, bronchitis, pneumonia, allergic rhinitis, eczema, parental asthma, and maternal smoking. Personal smoking and active adult asthma increased the impact of maternal smoking and childhood asthma, respectively, on the early below average, accelerated decline trajectory., Interpretation: We identified six potential FEV 1 trajectories, two of which were novel. Three trajectories contributed 75% of COPD burden and were associated with modifiable early-life exposures whose impact was aggravated by adult factors. We postulate that reducing maternal smoking, encouraging immunisation, and avoiding personal smoking, especially in those with smoking parents or low childhood lung function, might minimise COPD risk. Clinicians and patients with asthma should be made aware of the potential long-term implications of non-optimal asthma control for lung function trajectory throughout life, and the role and benefit of optimal asthma control on improving lung function should be investigated in future intervention trials., Funding: National Health and Medical Research Council of Australia; European Union's Horizon 2020; The University of Melbourne; Clifford Craig Medical Research Trust of Tasmania; The Victorian, Queensland & Tasmanian Asthma Foundations; The Royal Hobart Hospital; Helen MacPherson Smith Trust; and GlaxoSmithKline., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The risk of developing asthma in those with early food allergy is unknown, particularly when early life food allergy has resolved., Objective: To understand whether challenge-proven food allergy in infancy increases the risk of asthma at age 4 years, using data from a population-based cohort., Methods: A total of 5,276 12-month-old infants were recruited using a population-based sampling frame. Infants underwent skin prick test to egg, peanut, and sesame and those with a detectable skin prick test result had oral food challenges. At age 4 years, food challenges were repeated to determine persistence or resolution of food allergy. The association between food allergy and doctor-diagnosed asthma was examined using binomial regression in 2,789 participants., Results: Children with food allergy at age 1 year had an increased risk of asthma (1 food allergy: relative risk [RR], 1.69; 95% CI, 1.29-2.21; 2 or more food allergies: RR, 2.76; 95% CI, 1.94-3.92). The risk of asthma was highest in children with food allergy and coexistent eczema in infancy (RR, 2.87; 95% CI, 2.22-3.70). Transient food allergy and persistent food allergy were both associated with an increased risk of asthma (transient egg allergy: RR, 1.92; 95% CI, 1.46-2.51; persistent egg allergy: RR, 2.60; 95% CI, 1.76-3.85)., Conclusions: Asthma at age 4 years is twice as common in those with challenge-proven food allergy at age 1 year, irrespective of whether the food allergy subsequently resolves. Children with 2 or more food allergies and those with coexistent eczema were almost 3 times as likely to develop asthma compared with those with no food allergies., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Extensive research exists on arterial mechanical properties and how they change in disease conditions, but substantially less is known about venous mechanics in healthy and disease states. Although the mechanics of both vessel types are determined by the unique layered composition of the vessel wall, the precise distribution of the layers differs greatly between arteries and veins. Thus, vein mechanics must be analyzed and understood independently from those of arteries. This review discusses the compositional attributes that are unique to veins, how these attributes contribute to venous mechanics, and the alterations that occur to both composition and material properties during venous thrombosis and insufficiency. In general, changes to the venous wall during thrombosis increase wall stiffness and decrease extensibility. During venous insufficiency, however, both the stiffness and the extensibility of the venous wall decrease. Characterizing these changes is essential to better understand disease progression and build vein-specific devices for treating venous disease., Competing Interests: Conflict of Interest Disclosure: The authors have completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported.

Background: Peanut allergy (PA) is potentially life-threatening and generally persists for life. Recent data suggest the skin might be an important route of initial sensitization to peanut, whereas early oral exposure to peanut is protective. In mice regulatory T (Treg) cells are central to the development of food tolerance, but their contribution to the pathogenesis of food allergy in human subjects is less clear., Objective: We sought to quantify and phenotype CD4 + peanut-specific effector T (ps-Teff) cells and peanut-specific regulatory T (ps-Treg) cells in children with and without PA or PS., Methods: ps-Teff and ps-Treg cells were identified from peripheral blood of children with PA, children with PS, and nonsensitized/nonallergic (NA) school-aged children and 1-year-old infants based on upregulation of CD154 or CD137, respectively, after stimulation with peanut extract. Expression of cytokines and homing receptors was evaluated by using flow cytometry. Methylation at the forkhead box protein 3 (FOXP3) locus was measured as a marker of Treg cell stability., Results: Differential upregulation of CD154 and CD137 efficiently distinguished ps-Teff and ps-Treg cells. A greater percentage of ps-Teff cells from infants with PA and infants with PS expressed the skin-homing molecule cutaneous lymphocyte antigen, suggesting activation after exposure through the skin, compared with NA infants. Although ps-Teff cells in both school-aged and infant children with PA produced primarily T H 2 cytokines, a T H 1-skewed antipeanut response was seen only in NA school-aged children. The frequency, homing receptor expression, and stability of ps-Treg cells in infants and school-aged children were similar, regardless of allergic status., Conclusions: Exposure to peanut through the skin can prime the development of T H 2 ps-Teff cells, which promote sensitization to peanut, despite the presence of normal numbers of ps-Treg cells., (Published by Elsevier Inc.)

Functional mitral regurgitation (FMR) is an insidious and poorly understood condition affecting patients with myocardial disease. While current treatments reduce regurgitation, their ability to reverse mitral valve pathology is unclear. We utilized a pseudo-physiological flow loop to study how repair impacted valve composition. Porcine mitral valves were cultured in control geometry (native papillary muscle position and annular area) or high-tension FMR geometry (5 mm apical and 5 mm lateral displacement of papillary muscles, 65% increased annular area) for 2 weeks. To mimic repair, a reversal condition was created by returning one-week FMR conditioned valves to a non-regurgitant geometry and culturing for 1 week. Valve composition and material properties were analyzed. After two-week culture, FMR conditioned tissues were stiffer and stronger than control and underwent extensive fibrotic remodeling, with increased prolyl-4-hydroxylase, lysyl oxidase, matrix metalloproteinase-1, and decorin. The reversal condition displayed a heterogeneous, leaflet- and orientation-dependent response. Reversal-conditioned anterior leaflets and circumferential tissue sections continued to have significant fibrotic remodeling compared to control, whereas reversal-conditioned posterior leaflets, chordae tendineae, and radial tissue sections had significantly decreased remodeling compared to FMR-conditioned tissues. These findings suggest current repairs only partially reverse pathology, underscoring the need for innovation in the treatment of FMR.

Aims: To examine reports of anaphylaxis in Australasia from consumption of packaged food products with or without precautionary allergen labelling (PAL), where the known allergen triggers were not a listed ingredient., Methods: A questionnaire was sent to all members of the Australasian Society of Clinical Immunology and Allergy (n = 548). Participants were asked to complete a survey reporting whether they have had seen any patients over the last 3 months reporting anaphylaxis following ingestion of a packaged food where the suspected food allergen was not a listed ingredient., Results: Of the n = 548 members approached, n = 198 responded (response rate 36.1%).There were 14 reports of anaphylaxis to packaged foods (where the suspected allergen was not a listed ingredient), which met the case definition from a total of 198 respondents over the 9-month period. Of those reactions, 50.0% (confidence interval 95% 21-78) were reported from foods that did not have a PAL statement, and 50.0% (confidence interval 95% 21-78) were due to peanuts., Conclusion: Anaphylaxis to undeclared allergens was not rare and did not appear to depend on whether the product was labelled with precautionary advice. There is currently no reliable labelling system that can inform food-allergic consumers of safer food choices. Improvements in the regulation of food labelling with PAL are required., (© 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Iron overload (hemochromatosis) can cause serious, symptomatic disease that is preventable if detected early and managed appropriately. The leading cause of hemochromatosis in populations of predominantly European ancestry is homozygosity of the C282Y variant in the HFE gene. Screening of adults for iron overload or associated genotypes is controversial, largely because of a belief that severe phenotypes are uncommon, although cascade testing of first-degree relatives of patients is widely endorsed. We contend that severe liver disease (cirrhosis or hepatocellular cancer) is not at all uncommon among older males with hereditary hemochromatosis. Our review of the published data from a variety of empirical sources indicates that roughly 1 in 10 male HFE C282Y homozygotes is likely to develop severe liver disease during his lifetime unless iron overload is detected early and treated. New evidence from a randomized controlled trial of treatment allows for evidence-based management of presymptomatic patients. Although population screening for HFE C282Y homozygosity faces multiple barriers, a potentially effective strategy for increasing the early detection and prevention of clinical iron overload and severe disease is to include HFE C282Y homozygosity in lists of medically actionable gene variants when reporting the results of genome or exome sequencing.

Background: Although food allergy has probably risen over recent decades, recent reports suggest that the prevalence of food sensitization in the general population has not changed. However, this has not been analyzed in infants at high risk of food allergy., Objective: The objective of this study was to compare the prevalence of food sensitization in high-risk infants from 2 cohorts recruited 15 years apart in the same region., Methods: This study includes 620 high-risk infants with a family history of allergy (Melbourne Atopy Cohort Study [MACS]) born 1990-1994, and a subgroup of high-risk infants from the population-based HealthNuts study (n = 3,661/5,276), born 2006-2010. Both studies undertook skin prick tests (SPT) to peanut, egg, and milk at age 12 months. A logistic regression model generated adjusted prevalences to account for differences in sampling frame. SPT ≥ 95% positive predictive values (PPVs) for food allergy were used as proxies for food allergy., Results: The adjusted prevalence of sensitization in MACS was similar to the observed prevalence of sensitization in the high-risk subgroup of HealthNuts: 7.9% (95% confidence interval 6.8-8.9) and 7.9% (7.0-8.8) respectively for peanut, 15.0% (13.4-16.6) and 14.5% (13.4-15.7) respectively for egg, and 2.4% (1.6-3.1) and 2.6% (2.0-3.4) respectively for cow's milk. The prevalence of SPT ≥ 95% PPVs was similar between the 2 studies., Conclusions: The prevalence of food sensitization among high-risk infants has remained stable in Australia since the 1990s, despite the reported increase in food-related anaphylaxis in the same period. This discrepancy could be due to increased food allergy in the low-risk population, increased conversion of food sensitization to allergy, or increased number of high-risk infants. Alternatively, increased awareness or severity of reactions may have led to an apparent increase in food allergy., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Adolescents are at the highest risk of death from anaphylaxis, yet few population-based studies have described the frequencies and risk factors for allergic reactions caused by accidental allergen ingestion in this group., Methods: We describe the prevalence, frequency, and associated risk factors for recent adverse food reactions in 10- to 14-year-olds in Melbourne, Australia, recruited from a stratified, random, population-based sample of schools (SchoolNuts, n = 9663; 48% response rate). Self-reported food allergy and adverse reaction details, including anaphylaxis, were identified by using a student questionnaire over the past year., Results: Of 547 students with possible IgE-mediated food allergy, 243 (44.4%; 95% CI, 40.3% to 48.7%) reported a reaction to a food. Fifty-three (9.7%; 95% CI, 7.2% to 12.2%) students reported 93 anaphylaxis episodes. Peanut and tree nuts were the most common food triggers. Among students with current IgE-mediated food allergy, those with resolved or current asthma (adjusted odds ratio [aOR], 1.9 [95% CI, 1.1-1.3] and 1.7 [95% CI, 1.1-2.6]) and those with more than 2 food allergies (aOR, 1.9 [95% CI, 1.1-3.1]) were at greatest risk of any adverse food reaction, and those with nut allergy were most at risk of severe reactions (aOR, 2.9 [95% CI, 1.1-4.4]). Resolved or current asthma was not associated with increased risk of severe reactions (aOR, 0.8 [95% CI, 0.3-2.2] and 1.6 [95% CI, 0.7-3.7])., Conclusions: Adolescents with food allergy are frequently exposed to food allergens. Those with asthma and more than 2 food allergies were at the greatest risk for adverse food reactions. Those with nut allergies were most at risk of severe reactions., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Precautionary allergen labeling (PAL) also known as "may contain" labeling has been applied to many packaged food products around the world. PAL is a voluntary form of labeling whose original intent was to help ensure that packaged foods were as safe as possible for allergic consumers by alerting them to the possible presence of allergen residues resulting from the use of shared processing equipment, shared processing facilities, or other industry practices. However, the proliferation of PAL and the myriad of various phrasing used as PAL statements are confusing to consumers and serve to diminish their quality of life. Thus many allergic consumers are known to ignore PAL statements. Analytical surveys indicate that many PAL products contain no detectable allergen residues and are likely safe for allergic consumers. However, up to 8% of allergic consumers report having had reactions to the ingestion of PAL products. Clearly a better approach to labeling is needed that balances the health and safety considerations of allergic consumers with their desire to enjoy the widest possible array of foods available in the marketplace. This article presents an overview and discussion of the shortcomings of the current PAL system and explores why a new approach is required., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Despite the rising rates of anaphylaxis in older children and adolescents, risk factors for food allergy among this age group are understudied., Objective: The objective of this study was to investigate the risk factors for current adolescent food allergy using a population-based sample., Methods: The SchoolNuts study was a questionnaire survey among 10- to 14-year-old adolescents and their parents, followed by clinic evaluation including oral food challenge when food allergy was suspected from questionnaire response. We investigated the association between food allergy and demographic and environmental factors among a total of 4,991 adolescents using multiple logistic regression., Results: Males and those with early-onset eczema had a higher risk of current food allergy in adolescence (adjusted odds ratio [aOR], 1.55; 95% confidence interval [CI], 1.12-2.15 and aOR, 14.08; 95% CI, 10.25-19.33). Those with Asian parents had increased risk compared with those with Caucasian parents (aOR, 2.82; 95% CI, 1.91-4.16), whereas being born in Asia compared with being born in Australia had decreased risk (aOR, 0.16; 95% CI, 0.04-0.67). Family history risk was higher for those with multiple members versus only 1 member (aOR, 4.62; 95% CI, 2.75-7.74 and aOR, 2.32; 95% CI, 1.36-3.97, respectively). Dog exposure during the first 5 years of life was associated with a decreased risk (aOR, 0.58; 95% CI, 0.38-0.91)., Conclusions: Early-onset eczema, Asian background, and family history of allergic disease were associated with an increased risk of food allergy, whereas dog exposure in early life reduced the risk in 10- to14-year-old adolescents. Factors predicting food allergy risk in an adolescent population-based cohort appear remarkably similar to those predicting early-onset food allergy in infancy., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

This review summarizes the current state of play with regard to food allergy prevention. Food allergy prevention strategies focused on promoting timely introduction of allergenic foods (predominantly peanut) into the infant diet have recently been introduced in several countries. Additional prevention strategies currently under investigation include optimizing infant vitamin D levels, modulating the gut microbiota through use of probiotics, and preventing eczema to reduce the risk of food sensitization through a damaged skin barrier., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Dietary polyunsaturated fatty acids (PUFAs) have immunoregulatory properties. Breast milk is rich in PUFA, and it has been hypothesized that these PUFAs may be important in the aetiology of allergic diseases. Despite a growing body of evidence, the associations between breast milk PUFA and allergic disease have not previously been systematically reviewed., Methods: The search was performed in PubMed and EMBASE databases using breastfeeding, fatty acid and allergic disease terms. Two authors were involved in selecting papers for review according to the inclusion criteria and extracting information on study characteristics and measures of association. Only studies that reported numeric associations between concentration of breast milk fatty acids and allergic disease outcomes were included., Results: A total of 18 papers met the inclusion criteria, reporting results from 15 study populations. The majority were cohort studies (n=11), with data from only two case-control and two cross-sectional studies. Sample size varied between 30 and 352 participants, and follow-up time of the cohorts varied between 3 months and 14 years. Nine studies reported on eczema, seven reported on sensitization, and only five reported on asthma/wheeze. There was heterogeneity among studies in terms of presenting the association between PUFA and allergy; therefore, estimates could not be pooled. Only a few studies observed associations between n-3 and n-6 PUFAs and allergic disease, and the magnitude of this effect varied greatly., Conclusions: There is insufficient evidence to suggest that colostrum or breast milk polyunsaturated fatty acids influence the risk of childhood allergic diseases., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Aortic regurgitation is a prevalent, detrimental complication of left ventricular assist devices (LVADs). The altered hemodynamics of LVADs results in aortic valves (AVs) having distinct mechanical stimulation. Our hypothesis was that the altered AV hemodynamics modulates the valve cells and matrix, resulting in changes in valvular mechanical properties that then can lead to regurgitation., Methods: AVs were collected from 16 LVAD and 6 non-LVAD patients at time of heart transplant. Standard demographic and preoperative data were collected and comparisons between the two groups were calculated using standard statistical methods. Samples were analyzed using biaxial mechanical tensile testing, mass spectrometry-based proteomics, and transmission electron microscopy to assess ultrastructure., Results: The maximum circumferential leaflet strain in LVAD patients was less than in non-LVAD patients (0.35 ± 0.10MPa versus 0.52 ± 0.18 MPa, p = 0.03) with a trend of reduced radial strain (p = 0.06) and a tendency for the radial strain to decrease with increasing LVAD duration (p = 0.063). Numerous proteins associated with actin and myosin, immune signaling and oxidative stress, and transforming growth factor β were increased in LVAD patients. Ultrastructural analysis showed a trend of increased fiber diameter in LVAD patients (46.2 ± 7.2 nm versus 45.1 ± 6.9 nm, p = 0.10), but no difference in fiber density., Conclusions: AVs in LVAD patients showed decreased compliance and increased expression of numerous proteins related to valve activation and injury compared to non-LVAD patients. Further knowledge of AV changes leading to regurgitation in LVAD patients and the pathways by which they occur may provide an opportunity for interventions to prevent and/or reverse this detrimental complication., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Allergic diseases have increased dramatically in the developed world during the past few decades, yet the understanding of risk factors and effective prevention approaches remain limited. In this review, we summarize the evidence supporting the hypothesis that skin-barrier impairment and early-life atopic dermatitis (AD) could play a causal role in the development of sensitization and subsequent food allergies and allergic airways disease (allergic asthma and rhinitis). We further discuss the potential to target the skin barrier as a means to lower the incidence of allergic disease., Data Sources: Review of published literature., Study Selections: Narrative., Results: There is a strong link between AD and sensitization, food allergy, asthma, and allergic rhinitis, particularly AD that is severe and commences in the first 6 months of life. There also is emerging evidence that regular use of prophylactic emollients can significantly decrease the expression of AD, at least while treatment continues. Studies are exploring whether decreased AD expression might modulate the allergic response at a more fundamental level and potentially alter the association between early-life AD and subsequent development of food allergy and allergic airways disease., Conclusion: Although at this point there is only indirect evidence that early-life emollient use might prevent AD and food allergy, early studies are encouraging. The results of high-quality prevention trials that are in progress are eagerly anticipated. If found to be effective, then neonatal emollient use could be a simple public health measure to lower the incidence of AD, food allergies, and allergic airways disease in future generations., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Atopic diseases, including food allergy, have become a predominant cause of chronic illness among children in developed countries. In Australia, a rise in hospitalisations among infants coded as anaphylaxis to foods coincided with the replacement of whole-cell pertussis (wP) vaccine with subunit acellular pertussis (aP) vaccine on the national immunisation schedule in the late 1990s. Atopy is characterised by a tendency to mount T helper type 2 (Th2) responses to otherwise innocuous environmental antigens. Compared with infants who receive aP as their first pertussis vaccine, those who receive wP appear less likely to mount Th2 immune responses to either vaccine or extraneous antigens. We therefore speculate that removal of wP from the vaccine schedule contributed to the observed rise in IgE-mediated food allergy among Australian infants., Methods and Analysis: This is a retrospective individually matched case-control study among a cohort of Australian children born from 1997 to 1999, the period of transition from wP to aP vaccines; we include in the cohort children listed on Australia's comprehensive population-based immunisation register as having received a first dose of either pertussis vaccine by 16 weeks old. 500 cohort children diagnosed as having IgE-mediated food allergy at specialist allergy clinics will be included as cases. Controls matched to each case by date and jurisdiction of birth and regional socioeconomic index will be sampled from the immunisation register. Conditional logistic regression will be used to estimate OR (±95% CI) of receipt of wP (vs aP) as the first vaccine dose among cases compared with controls., Ethics and Dissemination: The study is approved by all relevant human research ethics committees: Western Australia Child and Adolescent Health Services (2015052EP), Women's and Children's Hospital (HREC/15/WCHN/162), Royal Children's Hospital (35230A) and Sydney Children's Hospital Network (HREC/15/SCHN/405). Outcomes will be disseminated through publication and scientific presentation., Trial Registration Number: NCT02490007., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Radiation therapy (RT) in the form of photons and protons is a well-established treatment for cancer. More recently, heavy charged particles have been used to treat radioresistant and high-risk cancers. Radiation treatment is known to cause cardiovascular disease (CVD) which can occur acutely during treatment or years afterward in the form of accelerated atherosclerosis. Radiation-induced cardiovascular disease (RICVD) can be a limiting factor in treatment as well as a cause of morbidity and mortality in successfully treated patients. Inflammation plays a key role in both acute and chronic RICVD, but the underling pathophysiology is complex, involving DNA damage, reactive oxygen species, and chronic inflammation. While understanding of the molecular mechanisms of RICVD has increased, the growing number of patients receiving RT warrants further research to identify individuals at risk, plans for prevention, and targets for the treatment of RICVD. Research on RICVD is also relevant to the National Aeronautics and Space Administration (NASA) due to the prevalent space radiation environment encountered by astronauts. NASA's current research on RICVD can both contribute to and benefit from concurrent work with cell and animal studies informing radiotoxicities resulting from cancer therapy. This review summarizes the types of radiation currently in clinical use, models of RICVD, current knowledge of the mechanisms by which they cause CVD, and how this knowledge might apply to those exposed to various types of radiation.

Food allergies manifest in a variety of clinical conditions within the gastrointestinal tract, skin and lungs, with the most dramatic and sometimes fatal manifestation being anaphylactic shock. Major progress has been made in basic, translational and clinical research, leading to a better understanding of the underlying immunological mechanisms that lead to the breakdown of clinical and immunological tolerance against food antigens, which can result in either immunoglobulin E (IgE)-mediated reactions or non-IgE-mediated reactions. Lifestyle factors, dietary habits and maternal-neonatal interactions play a pivotal part in triggering the onset of food allergies, including qualitative and quantitative composition of the microbiota. These factors seem to have the greatest influence early in life, an observation that has led to the generation of hypotheses to explain the food allergy epidemic, including the dual-allergen exposure hypothesis. These hypotheses have fuelled research in preventive strategies that seek to establish desensitization to allergens and/or tolerance to allergens in affected individuals. Allergen-nonspecific therapeutic strategies have also been investigated in a number of clinical trials, which will eventually improve the treatment options for patients with food allergy.

Background: Rising rates of food-induced anaphylaxis have recently been shown in the adolescent age group, following earlier descriptions of a rise in children younger than 5 years. However, few population-based studies have examined the prevalence of food allergy in adolescence using objective measures such as oral food challenge (OFC)., Objective: We sought to determine the prevalence of food allergy among a population-based sample of 10- to 14-year-old adolescents using clinical evaluation including OFC to confirm the diagnosis., Methods: Schools were randomly selected from greater metropolitan Melbourne, Australia. Students aged 10 to 14 years, and their parents, were asked to complete a questionnaire regarding the adolescent's food allergy or food-related reactions. Clinic evaluation, which consisted of skin prick tests and OFC where eligible, was undertaken if students were suspected to have current food allergy from parent response. Among 9816 students assessed, 5016 had complete parent response and clinic evaluation when eligible. An additional 4800 students had student questionnaires only., Results: The prevalence of clinic-defined current food allergy based on history, sensitization data, and OFC results was 4.5% (95% CI, 3.9-5.1), with the most common food triggers being peanut, 2.7% (95% CI, 2.3-3.2), and tree nut, 2.3% (95% CI, 1.9-2.8). Among the additional group of 4800 adolescents who had only self-reported food allergy status available, the prevalence of self-reported current food allergy was 5.5% (95% CI, 4.9-6.2), with peanut, 2.8% (95% CI, 2.3-3.3), and tree nut, 2.3% (95% CI, 1.9-2.8), the most common., Conclusions: Approximately 1 in 20 10- to 14-year-old school students in Melbourne has current food allergy. This high prevalence suggests that the previously reported rise in food-induced anaphylaxis in this age group may reflect an increasing prevalence of food allergy rather than simply increased reporting of anaphylaxis., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Food allergies are increasing globally, including numbers of allergens, the sensitization rate, and the prevalence rate. To protect food-allergic individuals in the community, food allergies need to be appropriately managed. This paper describes current Australian food allergen management practices. In Australia, the prevalence of food allergies, the anaphylaxis rate, and the fatal anaphylaxis rate are among the highest in the world. Interagency and stakeholder collaboration is facilitated and enhanced as Australia moves through past, current, and ongoing food allergen challenges. As a result, Australia has been a global leader in regulating the labeling of common allergens in packaged foods and their disclosure in foods not required to bear a label. Moreover, the food industry in Australia and New Zealand has developed a unique food allergen risk management tool, the Voluntary Incidental Trace Allergen Labelling program, which is managed by the Allergen Bureau. This paper summarizes insights and information provided by the major stakeholders involved to protect food-allergic consumers from any allergic reaction. Stakeholders include government; consumer protection, regulation, and enforcement agencies; the food industry; and food allergen testing and food allergen/allergy research bodies in Australia. The ongoing goal of all stakeholders in food allergen management in Australia is to promote best practice food allergen management procedures and provide a wide choice of foods, while enabling allergic consumers to manage their food allergies and reduce the risk of an allergic reaction.

Background: The iron overload disorder hereditary haemochromatosis is most commonly caused by HFE p.Cys282Tyr homozygosity. In the absence of results from any randomised trials, current evidence is insufficient to determine whether individuals with hereditary haemochromatosis and moderately elevated serum ferritin, should undergo iron reduction treatment. This trial aimed to establish whether serum ferritin normalisation in this population improved symptoms and surrogate biomarkers., Methods: This study was a multicentre, participant-blinded, randomised controlled trial done at three centres in Australia. We enrolled people who were homozygous for HFE p.Cys282Tyr, aged between 18 and 70 years, with moderately elevated serum ferritin, defined as 300-1000 μg/L, and raised transferrin saturation. Participants were randomly assigned, via a computer-generated random number, to undergo either iron reduction by erythrocytapheresis (treatment group) or sham treatment by plasmapheresis (control group). Randomisation was stratified by baseline serum ferritin (<600 μg/L or ≥600 μg/L), sex, and study site. Erythrocytapheresis and plasmapheresis were done every 3 weeks, the number of procedures and volume of red cells or plasma removed determined on the basis of each patient's haemoglobin, haematocrit, and serum ferritin concentration, as well their height and weight. In the erythrocytapheresis group, the target was to reduce serum ferritin to less than 300 μg/L. The number of procedures for the control group was based on the initial serum ferritin and prediction of decrease in serum ferritin of approximately 120 μg/L per treatment. The primary outcome was patient-reported Modified Fatigue Impact Scale (MFIS) score, measured at baseline and before unblinding. Analyses were by intention to treat, including the safety analysis. The trial is registered with ClinicalTrials.gov, number NCT01631708, and has been completed., Findings: Between Aug 15, 2012, and June 9, 2016, 104 participants were randomly assigned to the treatment (n=54) and control (n=50) groups, of whom 94 completed the study (50 in the treatment group and 44 in the control group). Improvement in MFIS score was greater in the treatment group than in the control group (mean difference -6·3, 95% CI -11·1 to -1·4, p=0·013). There was a significant difference in the cognitive subcomponent (-3·6, -5·9 to -1·3, p=0·0030), but not in the physical (-1·90 -4·5 to 0·63, p=0·14) and psychosocial (-0·54, -1·2 to 0·11, p=0·10) subcomponents. No serious adverse events occurred in either group. One participant in the control group had a vasovagal event and 17 participants (14 in the treatment group and three in the control group) had transient symptoms assessed as related to hypovolaemia. Mild citrate reactions were more common in the treatment group (32 events [25%] in 129 procedures) compared with the control group (one event [1%] in 93 procedures)., Interpretation: To our knowledge, this study is the first to objectively assess the consequences of iron removal in individuals with hereditary haemochromatosis and moderately elevated serum ferritin. Our results suggest that serum ferritin normalisation by iron depletion could be of benefit for all individuals with hereditary haemochromatosis and elevated serum ferritin levels., Funding: National Health and Medical Research Council (Australia)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose of Review: In the past decade, food allergy has been increasingly recognized as an important public health issue. The role of maternal and infant diet in the development of food allergy has been a major focus of research throughout this period. Recently, research in this area has moved from observational studies to intervention trials, and the findings from these trials have started to influence infant feeding guidelines. In this article, we review recent studies of dietary interventions for preventing food allergy, summarize current knowledge and discuss future research directions., Recent Findings: The latest result from an intervention trial shows that introduction of peanut in the first year of life reduces the risk of peanut allergy in high-risk infants. A systematic review and meta-analysis of intervention trials also suggests a protective effect of egg introduction from around 4 to 6 months of age for reducing the risk of egg allergy, with most studies conducted in high-risk infants. Despite several intervention trials involving modifications to the maternal diet, the effect of maternal diet during pregnancy and lactation in preventing food allergy remains unclear., Summary: Earlier introduction of allergenic foods is a promising intervention to reduce the risk of some food allergies in high-risk infants. Further work is needed to improve knowledge of how to prevent food allergy in the general population.

New tools are needed to enable rapid detection, identification, and reporting of infectious viral and microbial pathogens in a wide variety of point-of-care applications that impact human and animal health. We report the design, construction, and characterization of a platform for multiplexed analysis of disease-specific DNA sequences that utilizes a smartphone camera as the sensor in conjunction with a hand-held "cradle" that interfaces the phone with a silicon-based microfluidic chip embedded within a credit-card-sized cartridge. Utilizing specific nucleic acid sequences for four equine respiratory pathogens as representative examples, we demonstrated the ability of the system to utilize a single 15 μL droplet of test sample to perform selective positive/negative determination of target sequences, including integrated experimental controls, in approximately 30 min. Our approach utilizes loop-mediated isothermal amplification (LAMP) reagents predeposited into distinct lanes of the microfluidic chip, which when exposed to target nucleic acid sequences from the test sample, generates fluorescent products that when excited by appropriately selected light emitting diodes (LEDs), are visualized and automatically analyzed by a software application running on the smartphone microprocessor. The system achieves detection limits comparable to those obtained by laboratory-based methods and instruments. Assay information is combined with the information from the cartridge and the patient to populate a cloud-based database for epidemiological reporting of test results.

The newly revised Australian Infant Feeding Guidelines recommends that all infants, including those at high risk of allergy, be introduced foods traditionally considered allergenic (such as peanut butter, dairy, wheat and egg) within the first year of life. High-risk infants are those with early onset eczema (<3-months old) or with moderate to severe eczema not responding to treatment (<6-months old). Eczema can also represent a symptom of allergy presentation and the recommended introduction of some foods in this group may lead to allergic reactions at home. Although there have been no reported deaths from gradual food introduction to infants at home and cohort studies have only reported mild to moderate reactions, there is anecdotal evidence that more severe reactions can occur rarely. Allergic reactions, even if they are not life-threatening, can be a terrifying experience for parents. Dermatologists play an important role when dealing with high-risk infants in promoting the message of early allergenic food introduction yet also instigating appropriate allergy testing when necessary. This short review aims to provide an update to Australasian dermatologists on the newly revised Australian Infant Feeding Guidelines and provide a food allergy screening pathway for high-risk infants prior to commencement of allergenic foods., (© 2017 The Australasian College of Dermatologists.)

Background: Infant feeding in the first postnatal year of life has an important role in an infant's risk of developing food allergy. Consumer infant feeding advice is diverse and lacks consistency., Aim: The Australian Infant Feeding Summit was held with the aim of achieving national consensus on the wording of guidelines for infant feeding and allergy prevention., Methods: Two meetings were hosted by the Centre for Food and Allergy Research, the Australasian Society of Clinical Immunology and Allergy, and the Australian National Allergy Strategy. The first meeting of 30 allergy researchers, clinicians, and consumers assessed the evidence. The second consensus meeting involved 46 expert stakeholders including state and federal health care agencies, consumers, and experts in allergy, infant feeding, and population health., Results: Partner stakeholders agreed on consensus wording for infant feeding advice: CONCLUSIONS: Consensus was achieved in a context in which there is a high prevalence of food allergy. Guidelines for other countries are being updated. Provision of consistent wording related to infant feeding to reduce food allergy risk will ensure clear consumer advice., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Precautionary allergen labelling (PAL) has resulted in consumer confusion. Previous research has shown that interpretive labels (using graphics, symbols, or colours) are better understood than the traditional forms of labels. In this study, we aimed to understand if consumers would use interpretive labels (symbol, mobile phone application and a toll-free number) with or without medical advice that was advocated by the food industry rather than the normal PAL. This is relevant information for industry and clinicians as it provides an insight into the food allergic perception regarding PAL.

Aortic valve disease (AVD) is one of the leading causes of cardiovascular mortality. Abnormal expression of hyaluronan (HA) and its synthesizing/degrading enzymes have been observed during latent AVD however, the mechanism of impaired HA homeostasis prior to and after the onset of AVD remains unexplored. Transforming growth factor beta (TGFβ) pathway defects and biomechanical dysfunction are hallmarks of AVD, however their association with altered HA regulation is understudied. Expression of HA homeostatic markers was evaluated in diseased human aortic valves and TGFβ1-cultured porcine aortic valve tissues using histology, immunohistochemistry and Western blotting. Further, porcine valve interstitial cell cultures were stretched (using Flexcell) and simultaneously treated with exogenous TGFβ1±inhibitors for activated Smad2/3 (SB431542) and ERK1/2 (U0126) pathways, and differential HA regulation was assessed using qRT-PCR. Pathological heavy chain HA together with abnormal regional expression of the enzymes HAS2, HYAL1, KIAA1199, TSG6 and IαI was demonstrated in calcified valve tissues identifying the collapse of HA homeostatic machinery during human AVD. Heightened TSG6 activity likely preceded the end-stage of disease, with the existence of a transitional, pre-calcific phase characterized by HA dysregulation. TGFβ1 elicited a fibrotic remodeling response in porcine aortic valves similar to human disease pathology, with increased collagen and HYAL to HAS ratio, and site-specific abnormalities in the expression of CD44 and RHAMM receptors. Further in these porcine valves, expression of HAS2 and HYAL1 was found to be differentially regulated by the Smad2/3 and ERK1/2 pathways, and CD44 expression was highly responsive to biomechanical strain. Leveraging the regulatory pathways that control both HA maintenance in normal valves and early postnatal dysregulation of HA homeostasis during disease may identify new mechanistic insight into AVD pathogenesis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Aim: The aim of this study was to describe antibiotic exposure in Australian infants during the first year of life, focusing on antibiotic class, indication, risk factors associated with exposure and comparison with international counterparts., Methods: The Barwon Infant Study is a birth cohort study (n = 1074) with an unselected antenatal sampling frame from a large regional centre in Victoria, Australia. Longitudinal data on infection and medication were collected at 1, 3, 6, 9 and 12 months by parental questionnaire and from general practitioner and hospital records. Predictors of questionnaire non-completion were identified. A total of 660 infants with complete serial data were comprehensively examined. Antibiotic exposure was calculated as (i) antibiotic prescriptions and (ii) antibiotic days-exposed per person-year., Results: Mean antibiotic prescription rate was 0.92 prescriptions (95% confidence interval (CI), 0.83-1.02) per person-year, with the highest rates in those aged <1 month (1.50 (95% CI, 1.09-1.91) per person-year). A total of 50.0% of infants were exposed to at least one antibiotic in their first year of life. Increasing number of siblings was associated with increased antibiotic exposure. Penicillin with extended spectrum (365 of 661 antibiotic prescriptions, 52.6%) and cephalosporins (12.0%) were the most frequently prescribed antibiotics. One fifth of antibiotics were prescribed for respiratory tract infections and bronchiolitis., Conclusion: Australian infants in this large population-based study are exposed to considerably more antibiotics than the majority of their international counterparts. Interventions aimed at addressing avoidable prescribing by medical practitioners and modifiable risk factors associated with antibiotic exposure may reduce antibiotic use., (© 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: A defective skin barrier is hypothesized to be an important route of sensitization to dietary antigens and may lead to food allergy in some children. Missense mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions., Objective: To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy., Method: We genotyped 71 "tag" single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these individuals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent sample group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components., Results: SPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery sample (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also., Conclusions: We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Aim: Early feeding plays an important role in programming the immune system, particularly the risk of food allergy. There are many infant feeding guides published for consumers available in Australia, with most based on the National Health and Medical Research Council (NHMRC) 2012 Infant Feeding Guidelines for Health Workers and the Australasian Society of Clinical Immunology and Allergy (ASCIA) Infant Feeding Advice for allergy prevention. We sought to compare allergy-specific content of infant feeding educational material written for parents with these two documents., Methods: Australian websites of children's hospitals, early child health organisations and consumer groups providing information about diet during pregnancy, breastfeeding and early infancy were compared with NHMRC and ASCIA guidelines., Results: Twenty-five sets of infant feeding information were identified. Food allergy was discussed in 18 resources. Recommended length of exclusive breastfeeding and timing of commencing solid foods was consistently around 6 months, with some variation in wording. Advice regarding to include and not delay introduction of common allergens into babies' diets was generally consistent with NHMRC and ASCIA recommendations, however the audit identified some resources that still recommended delayed introduction of common allergens., Conclusion: As consumers have access to a plethora of health information it is imperative that information about infant feeding from health-care authorities is simple, evidence-based and consistent to avoid confusion. Use of consensus wording related to infant feeding guidelines to prevent allergies will provide clear messages related to the timing of introduction to solid foods and inclusion of allergens in the early diet., (© 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Although wool is commonly believed to cause irritant (non-immune) and hypersensitivity (immune) cutaneous reactions, the evidence basis for this belief and its validity for modern garments have not been critically examined. Publications from the last 100 years, using MEDLINE and Google Scholar, were analysed for evidence that wool causes cutaneous reactions, both immune-mediated (atopic dermatitis exacerbation, contact urticaria, allergic contact dermatitis) and non-immune-mediated (irritant contact dermatitis, itch). Secondary aims of this paper were to examine evidence that lanolin and textile-processing additives (formaldehyde, chromium) cause cutaneous reactions in the context of modern wool-processing techniques. Current evidence does not suggest that wool-fibre is a cutaneous allergen. Furthermore, contact allergy from lanolin, chromium and formaldehyde is highly unlikely with modern wool garments. Cutaneous irritation from wool relates to high fibre diameters (≥ 30-32 µm). Superfine and ultrafine Merino wool do not activate sufficient c-fibres to cause itch, are well tolerated and may benefit eczema management.