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BACKGROUND: The beneficial off-target effects of Bacille Calmette-Guérin (BCG) vaccination potentially include protection against allergy. OBJECTIVE: In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants. METHODS: In this randomised controlled trial, 1272 neonates were allocated to BCG-Denmark vaccine (0.05 mL intradermal dose) or no BCG at birth. Randomisation was stratified by recruitment site, mode of delivery and plurality of birth. The primary outcome was the incidence of atopic sensitisation determined by skin prick test at 1 year of age. Food allergy was determined by 3-monthly online questionnaires and oral food challenges. Data were analysed by intention-to-treat using binary regression. CLINICALTRIALS: gov (NCT01906853). RESULTS: Atopic sensitisation during the first year of life was 22.9% among infants in the BCG group and 18.9% in the control group (adjusted risk difference (aRD) 3.8% (95% CI -1.5 to 9.1) after multiple imputation). Clinical food allergy was similar between infants in the BCG and control groups (9.8% vs. 9.6%; aRD 0.2, 95% CI -3.4 to 3.8). An interaction was observed between the primary outcome and maternal history of BCG vaccination. No interaction was observed for the additional prespecified potential effect modifiers tested (sex, delivery mode, family history of any allergy, season of birth, hepatitis B vaccination at randomisation, BCG scar and age at BCG administration). CONCLUSIONS AND CLINICAL RELEVANCE: Neonatal BCG-Denmark vaccination does not protect against atopic sensitisation or clinical food allergy in the first year of life.

Many governments and organisations are currently aligning many aspects of their policies and practices to the sustainable development goals (SDGs). Achieving the SDGs should increase social-ecological resilience to shocks like climate change and its impacts. Here, we consider the relationship amongst the three elements—the SDGs, social-ecological resilience and climate change—as a positive feedback loop. We argue that long-term memory encoded in historical, archaeological and related ‘palaeo-data’ is central to understanding each of these elements of the feedback loop, especially when long-term fluctuations are inherent in social-ecological systems and their responses to abrupt change. Yet, there is scant reference to the valuable contribution that can be made by these data from the past in the SDGs or their targets and indicators. The historical and archaeological records emphasise the importance of some key themes running through the SDGs including how diversity, inclusion, learning and innovation can reduce vulnerability to abrupt change, and the role of connectivity. Using paleo-data, we demonstrate how changes in the extent of water-related ecosystems as measured by indicator 6.6.1 may simply be related to natural hydroclimate variability, rather than reflecting actual progress towards Target 6.6. This highlights issues associated with using SDG indicator baselines predicated on short-term and very recent data only. Within the context of the contributions from long-term data to inform the positive feedback loop, we ask whether our current inability to substantively combat anthropogenic climate change threatens achieving both the SDGS and enhanced resilience to climate change itself. We argue that long-term records are central to understanding how and what will improve resilience and enhance our ability to both mitigate and adapt to climate change. However, for uptake of these data to occur, improved understanding of their quality and potential by polic

BACKGROUND: Bacille Calmette-Guérin (BCG) vaccine could play a role in counteracting the rising prevalence of atopic diseases, through its beneficial off-target effects. We aimed to determine whether neonatal BCG vaccination reduces the incidence of eczema in infants. METHODS: Randomized controlled trial with 1272 infants allocated to receive BCG-Denmark or no BCG at birth. The primary outcome was the 12-month incidence of eczema based on 3-monthly questionnaires. Eczema was also assessed at a 12-month clinic visit. ClinicalTrial.gov: NCT01906853. RESULTS: The 12-month eczema incidence was 32.2% in the BCG group compared with 36.6% in the control group (adjusted risk difference (aRD) -4.3%, 95% CI -9.9% to 1.3%, multiple imputation model). In addition, comparing infants in the BCG group with the control group, 15.7% vs. 19.2% had eczema lesions at the 12-month visit (aRD -3.5%, 95% CI -8.0% to 1.0%); 35.7% vs. 39.0% reported using topical steroids (aRD -3.3, 95% CI -9.2 to 2.7); and 7.3% vs. 10.2% had severe eczema scores (aRD -3.0%, 95% CI -8.8% to 2.7%). In 344 high-risk infants (two atopic parents), the 12-month eczema incidence was 35.3% in the BCG group compared with 46.8% in the control group (aRD -11.5%, 95% CI -21.9% to -1.2%; number needed to treat 8.7, 95% CI 4.6 to 83.3). CONCLUSION: There is insufficient evidence to recommend neonatal BCG vaccination in all infants for the prevention of eczema in the first year of life; however, a modest beneficial effect was observed among high-risk infants. A single dose of BCG-Denmark soon after birth could reduce the incidence of eczema in infants with two atopic parents.

AIM: Adrenaline auto-injector (AAI) dispensing data, a community-based proxy for number of individuals at risk of anaphylaxis, provides complementary information on time trends of anaphylaxis risk in addition to hospital admission data. We examined trends of AAI dispensing over a 10-year period (from January 2005 to December 2014) in Australia. METHODS: Individuals with dispensed AAI were identified from a 10% random sample of Australian Pharmaceutical Benefits Scheme (PBS) data. PBS is the Australian national drug subsidy programme covering all Australians. Cumulative incidence and incidence rates of individuals with AAI were calculated. We assessed difference by age, sex, state and time trends. RESULTS: The cumulative incidence of individuals with AAI in 2005-2014 was 75.43/100 000 (95%CI 75.07-75.80/100 000). Incidence rate of individuals with AAI increased from 2005 to 2014 (from 71.47 to 82.07 per 100 000 person-years) although this varied by state. Over the time assessed, there was a shift to more prescriptions being provided by general practitioners (GP) rather than specialists. Children (0-19 years) were more likely to have been prescribed an AAI from a specialist and adults from a GP. CONCLUSION: Overall, an increase in dispensed AAI mirrored other evidence for a rising prevalence of allergy. This increase could also reflect changes in prescribing practices or increased awareness and education of health-care professionals on anaphylaxis and indications for prescribing AAI. The rising rate of AAI prescribed by GPs compared to decreasing rates by specialists suggests a changing response of the Australian health-care system to the increased burden of anaphylaxis.

Abstract Background Bacille Calmette-Guérin (BCG) vaccination has beneficial off-target effects that may include protecting against non-mycobacterial infectious diseases. We aimed to determine whether neonatal BCG vaccination reduces lower respiratory tract infections (LRTI) in infants in the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) trial. Methods In this investigator-blinded trial, neonates in Australia were randomized to receive BCG-Denmark vaccination or no BCG at birth. Episodes of LRTI were determined by symptoms reported in parent-completed, 3-month questionnaires over the first year of life. Data were analyzed by intention-to-treat using binary regression. Results A total of 1272 neonates were randomized to the BCG vaccination (n = 637) or control (n = 635) group. The proportion of participants with an episode of LRTI in the first year of life among BCG-vaccinated infants was 54.8% compared to 58.0% in the control group, resulting in a risk difference of −3.2 (95% confidence interval, −9.0 to 2.6) after multiple imputation. There was no interaction observed between the primary outcome and sex, maternal BCG, or the other prespecified effect modifiers. Conclusions Based on the findings of this trial, there is insufficient evidence to support the use of neonatal BCG vaccination to prevent LRTI in the first year of life in high-income settings.

Globally, many biomes are being impacted by significant shifts in total annual rainfall as well as increasing variability of rainfall within and among years. Such changes can have potentially large impacts on plant productivity and growth, but remain largely unknown, particularly for much of the Southern Hemisphere. We investigate how growth of the widespread conifer, Callitris columellaris varied with inter-annual variation in the amount, intensity and frequency of rainfall events over the last century and between semi-arid (<500 mm mean annual rainfall) and tropical (>800 mm mean annual rainfall) biomes in Australia. We used linear and polynomial regression models to investigate the strength and shape of the relationships between growth (ring width) and rainfall. At semi-arid sites, growth was strongly and linearly related to rainfall amount, regardless of differences in the seasonality and intensity of rainfall. The linear shape of the relationship indicates that predicted future declines in mean rainfall will have proportional negative impacts on long-term tree growth in semi-arid biomes. In contrast, growth in the tropics showed a weak and asymmetrical ('concave-down') response to rainfall amount, where growth was less responsive to changes in rainfall amount at the higher end of the rainfall range (>1250 mm annual rainfall) than at the lower end (<1000 mm annual rainfall). The asymmetric relationship indicates that long-term growth rates of Callitris in the tropics are more sensitive to increased inter-annual variability of rainfall than to changes in the mean amount of rainfall. Our findings are consistent with observations that the responses of vegetation to changes in the mean or variability of rainfall differ between mesic and semi-arid biomes. These results highlight how contrasting growth responses of a widespread species across a hydroclimatic gradient can inform understanding of potential sensitivity of different biomes to climatic variability and chan

Rainfall regimes in many parts of the world have become increasingly dominated by fewer, but more extreme, rainfall events. Understanding how tree growth responds to changes in the frequency and intensity of rain events is critical to predicting how climate change will impact on forests and woodlands in the future. In this study, we used five tree‐ring records of the native Australian conifer Callitris columellaris that span a large (> 20°) latitudinal and climatic gradient from the mesic (tropical) north to the xeric (semi‐arid) south of Australia to investigate how inter‐annual and spatial variation in the delivery of rainfall (the intensity and frequency of rain events) influences tree growth. In semi‐arid biomes (~300–400 mm rainfall annually), tree growth is most strongly related to the amount of rainfall from heavy (> 75th percentile) rain days or the number of extreme (> 90th percentile) rain days, regardless of differences in the seasonal distribution and average intensity of rainfall among sites. Our findings also indicate that there is likely a minimum threshold amount of daily rainfall (~5 mm) that is required to stimulate tree growth in the semi‐arid zone. In contrast, in the tropics (> 800 mm annual rainfall), inter‐annual variation in growth is best explained by total growing season rainfall or the number of rain days > ~5 mm (~50th percentile of rain days) rather than extreme rainfall. Our findings indicate that not all rain events are important for driving tree growth, which has important implications for interpreting climatic signals in tree rings. Our findings also indicate that projected increases in the intensity of extreme rain events are likely to have contrasting impacts on tree growth across biomes, with greater and positive impacts on growth in semi‐arid biomes and potentially negative impacts on growth in tropical biomes of Australia.

Compound climate extremes (CCEs) can have significant and persistent environmental impacts on ecosystems. However, knowledge of the occurrence of CCEs beyond the past ~ 50 years, and hence their ecological impacts, is limited. Here, we place the widespread 2015-16 mangrove dieback and the more recent 2020 inland native forest dieback events in northern Australia into a longer historical context using locally relevant palaeoclimate records. Over recent centuries, multiple occurrences of analogous antecedent and coincident climate conditions associated with the mangrove dieback event were identified in this compilation. However, rising sea level-a key antecedent condition-over the three decades prior to the mangrove dieback is unprecedented in the past 220 years. Similarly, dieback in inland forests and savannas was associated with a multi-decadal wetting trend followed by the longest and most intense drought conditions of the past 250 years, coupled with rising temperatures. While many ecological communities may have experienced CCEs in past centuries, the addition of new environmental stressors associated with varying aspects of global change may exceed their thresholds of resilience. Palaeoclimate compilations provide the much-needed longer term context to better assess frequency and changes in some types of CCEs and their environmental impacts.

BACKGROUND: In Western countries, Asian children have higher food allergy risk than Caucasian children. The early-life environmental exposures for this discrepancy are unclear. We aimed to compare prevalence of food allergy and associated risk factors between Asian children in Singapore and Australia. METHODS: We studied children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort (n = 878) and children of Asian ancestry in the HealthNuts cohort (n = 314). Food allergy was defined as a positive SPT ≥3 mm to egg or peanut AND either a convincing history of IgE-mediated reaction at 18 months (GUSTO) or a positive oral food challenge at 14-18 months (HealthNuts). Eczema was defined as parent-reported doctor diagnosis. RESULTS: Food allergy prevalence was 1.1% in Singapore and 15.0% in Australia (P<0.001). Egg introduction was more often delayed (>10 months) in Singapore (63.5%) than Australia (16.3%; P<0.001). Prevalence of early-onset eczema (<6 months) was lower in Singapore (8.4%) than Australia (30.5%) (P<0.001). Children with early-onset eczema were more likely to have food allergy than those without eczema in Australia [aOR 5.11 (2.34-11.14); P<0.001] and Singapore [aOR4.00 (0.62-25.8); P = 0.145]. CONCLUSIONS: Among Asian children, prevalence of early-onset eczema and food allergy was higher in Australia than Singapore. Further research with larger sample sizes and harmonized definitions of food allergy between cohorts is required to confirm and extend these findings. Research on environmental factors influencing eczema onset in Australia and Singapore may aid understanding of food allergy pathogenesis in different parts of the world.

In the Australian semi-arid–arid zone, hydrological records are typically only 40–60 years long, prohibiting an understanding of long-term hydrological variability. Kati-Thanda – Lake Eyre Basin (KT-LEB), is the fifth largest terminal lake in the world, experiences highly variable flows and supports myriad flora and fauna. The opportunistic and highly irregular growth of trees in KT-LEB means that tree-ring records have not been developed in the region. E. coolabah is a keystone species in the KT-LEB and can live for more than 300 years. In this study, we find that trees in the riparian zone exhibit larger and more diffuse vessels compared to trees on the flood plain. 14C dating indicates that clear temporal variations in vessel size and density are synchronous across trees at the same site and consistent with changes in hydrological conditions recorded in instrumental records. More diffuse and larger vessels in the floodplain trees are congruous with wetter events, while bands of wood with smaller and denser vessels co-occur with drier conditions. These results suggest the species has potential as a high-resolution, albeit not annual, palaeohydrological indicator in the semi arid–arid zone - potentially a major step forward in deriving palaeohydrological tree-ring records for this region.

In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella, a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort (n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal samples shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri. Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri.

BACKGROUND: High folate status in pregnancy has been implicated in the increased prevalence of allergic disease, but there are no published data relating directly measured folate status in pregnancy to challenge-proven food allergy among offspring. The study aim was to examine the association between red blood cell (RBC) folate status in trimester three of pregnancy and allergic disease among offspring. METHODS: Red blood cell folate levels were measured at 28-32 weeks' gestation in a prospective birth cohort (n = 1074). Food allergy outcomes were assessed in 1-year-old infants by skin prick testing and subsequent food challenge. Eczema was assessed by questionnaire and clinical review. High trimester three RBC folate was defined as greater than (>) 1360 nmol/L. Binomial regression was used to examine associations between trimester three RBC folate and allergic outcomes, adjusting for potential confounders. RESULTS: Red blood cell folate levels were measured in 88% (894/1064) of pregnant women. The mean concentration was 1695.6 nmol/L (standard deviation 415.4) with 82% (731/894) >1360 nmol/L. There was no evidence of either linear or non-linear relationships between trimester three RBC folate and allergic outcomes, nor evidence of associations between high RBC folate and food allergy (adjusted risk ratio (aRR) 2.89, 95% CI 0.90-9.35), food sensitization (aRR 1.72, 95% CI 0.85-3.49), or eczema (aRR 0.97, 95% CI 0.67-1.38). CONCLUSION: The majority of pregnant women in this study had high RBC folate levels. There was no evidence of associations between trimester three RBC folate and food allergy, food sensitization, or eczema among the offspring, although larger studies are required.

BACKGROUND AND OBJECTIVE: As caesarean delivery and childhood allergy continue to rise, their inter-relationships may change. We examined whether caesarean delivery predicts allergic disease and impaired lung function in two contemporary harmonised population-based cohorts. METHODS: Parent-reported asthma and eczema data were drawn from two prospective Australian infant cohorts, HealthNuts (n=5276, born 2006-2010) and the Longitudinal Study of Australian Children (LSAC, n=5107, born 2003-2004) at age 6-7 years, and spirometric lung function from LSAC's Child Health CheckPoint (n=1756) at age 11-12 years. Logistic regression estimated associations between delivery mode and current asthma and eczema at 6-7 years, and linear regression examined lung function at 11-12 years. Models were adjusted for potential confounding factors. RESULTS: Complete case analysis included 3135 HealthNuts and 3654 LSAC children (32.2% and 30.9% born by caesarean, respectively). An association was evident between caesarean delivery and asthma at age 6-7 years in HealthNuts (adjusted OR (aOR) 1.25, 95% CI 1.00 to 1.57) but not in LSAC (aOR 1.05, 95% CI 0.86 to 1.28), while neither study showed clear associations with eczema (HealthNuts: aOR 1.09, 95% CI 0.88 to 1.35; LSAC: aOR 0.89, 95% CI 0.69 to 1.15). Spirometric lung function parameters at age 11-12 years were similar by delivery mode. Associations were not modified by duration of breast feeding, maternal history of asthma/eczema, childcare attendance, number of older siblings or pet exposure. CONCLUSIONS: In two unselected populations using harmonised protocols, the likely association of caesarean delivery with developing childhood allergy was small.

BACKGROUND: Despite an increasing number of publications from individual countries and regions, there is still no systematic review of the global epidemiology of anaphylaxis in the general paediatric population. METHODS: We conducted a systematic review, using a protocol registered and published with the international prospective register of systematic reviews (PROSPERO). Results were reported following PRISMA guidelines. The search strategy was designed in Medline (ovid) and modified for Embase (ovid) and PubMed. Papers were screened by two independent reviewers following selection and exclusion criteria. Data extraction and risk of bias assessment were completed by the same two reviewers. Studies in adults only or those that did not report data in children separately were excluded. RESULTS: A final total of 59 articles were included. Of these, 5 reported cumulative incidence, 39 reported incidence rate and 17 reported prevalence data. The incidence of anaphylaxis in children worldwide varied widely, ranging from 1 to 761 per 100 000 person-years for total anaphylaxis and 1 to 77 per 100 000 person-years for food-induced anaphylaxis. The definition of anaphylaxis from NIAID/FAAN was the most commonly used. Gender and ethnicity were demographic risk factors associated with anaphylaxis in children. Increasing total or food-induced anaphylaxis incidence over time was reported by 19 studies. CONCLUSION: The reported incidence of anaphylaxis in children varied widely. Studies in developing countries are underrepresented. To accurately compare anaphylaxis incidence between countries and investigate the time trends, further studies using a standardized definition across different countries are required.

INTRODUCTION: The skin is an important barrier against environmental allergens, but infants have relatively impaired skin barrier function. There is evidence that impaired skin barrier function increases the risk of allergic sensitisation, atopic dermatitis (AD) and food allergy. We hypothesise that regular prophylactic use of emollients, particularly those that are designed to improve skin barrier structure and function, will help prevent these conditions. With the aim of determining if application of a ceramide-dominant emollient two times per day reduces the risk of AD and food allergy, we have commenced a multicentre phase III, outcome assessor blinded, randomised controlled trial of this emollient applied from birth to 6 months. METHODS AND ANALYSIS: Infants (n=760) with a family history of allergic disease will be recruited from maternity hospitals in Melbourne. The primary outcomes are as follows: the presence of AD, assessed using the UK Working Party criteria, and food allergy using food challenge, in the first 12 months of life as assessed by a blinded study outcome assessor. Secondary outcomes are as follows: food sensitisation (skin prick test), skin barrier function, AD severity, the presence of new onset AD after treatment cessation (between 6 and 12 months) and the presence of parent reported AD/eczema. Recruitment commenced in March 2018. ETHICS AND DISSEMINATION: The PEBBLES Study is approved by the Human Research Ethics Committees of the Royal Children's Hospital (RCH) (#37090A) and the Mercy Hospital for Women (2018-008). Parents or guardians will provide written informed consent. Outcomes will be disseminated through peer-reviewed publications and presented at scientific conferences. TRIAL REGISTRATION NUMBERS: ACTRN12617001380381 and NCT03667651.

Systematic reviews of nutritional interventions indicate limited efficacy in reducing childhood obesity, but their blanket conclusions could obscure promising components. This narrative review sought more detail on effective components within nutrition-related interventions involving children aged 2 to 11 years. In May 2016, the World Health Organization (WHO) searched the Cochrane Library and PubMed for relevant reviews. From 36 reviews, we screened 182 nutrition-related randomized trials for inclusion. We then reviewed those that reported at least 1 statistically significant (P < 0.05) treatment benefit on body weight and/or composition outcomes at their longest follow-up assessment. Fourteen trials met inclusion criteria (median n = 554; mean intervention duration = 10.8 mo; follow-up = 4.4 mo). "Effective" approaches included environmental changes such as school water fountain installations and cafeteria menu changes and possibly less sustainable strategies such as health education lessons. However, effect sizes even of these selected significant treatment benefits were modest-significant body mass index z-score effects range from -0.1 to -0.2. Each trial was associated with very small improvements in body composition. Because this is a "best-case" scenario (reflecting our design), trialists should rigorously test these strategies alone and possibly together; be open to novel strategies; and ensure that each strategy is culturally relevant and self-sustainable.

Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preeclampsia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preeclamptic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4+ T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preeclampsia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preeclampsia and immune development in offspring.

findings from systematic reviews into infant feeding and later adiposity are largely negative. World Health Organization (WHO) is auspicing Healthy Life Trajectories Initiative (HeLTI), a suite of trials aiming to prevent overweight/obesity in childhood. To inform planning, this narrative review sought to detail potentially effective components of nutrition-related interventions involving children aged 0 to 2 years. Systematic searches of PubMed and the Cochrane Library (2006-2016) identified 108 systematic reviews. These included 31 randomized trials in the age group of interest. Of these, 11 reported greater than or equal to 1 statistically significant (P < 0.05) benefit on body weight and/or composition. Six multicomponent trials whose interventions incorporated education to promote breastfeeding (four trials), responsive feeding (two trials), and healthy diet (eg, increasing fruit and vegetables and limiting unhealthy snack foods; five trials), delivered through home visits or at baby health clinics, reported relative reductions in body mass index (BMI) at the end of intervention. Early benefits were not maintained in the two trials reporting follow-up 1 to 3 years later. Other potentially effective approaches included lower protein formulas in formula-fed infants and education around reducing sugar-sweetened beverages. There is some evidence that infant feeding interventions can have a transient positive impact on a child's BMI. It is not known whether ongoing intervention can avoid the subsequent expected wash-out.

BACKGROUND: The genetic determinants of food allergy have not been systematically reviewed. We therefore systematically reviewed the literature on the genetic basis of food allergy, identifying areas for further investigation. METHODS: We searched three electronic databases (MEDLINE, EMBASE and PubMed) on 9 January 2018. Two authors screened retrieved articles for review according to inclusion criteria and extracted relevant information on study characteristics and measures of association. Eligible studies included those that reported an unaffected nonatopic control group, had genetic information and were carried out in children. RESULTS: Of the 2088 studies retrieved, 32 met our inclusion criteria. Five were genome-wide association studies, and the remaining were candidate gene studies. Twenty-two of the studies were carried out in a predominantly Caucasian population with the remaining 10 from Asian-specific populations or unspecified ethnicity. We found FLG, HLA, IL10, IL13, as well as some evidence for other variants (SPINK5, SERPINB and C11orf30) that are associated with food allergy. CONCLUSIONS: Little genetic research has been carried out in food allergy, with FLG, HLA and IL13 being the most reproducible genes for an association with food allergy. Despite promising results, existing genetic studies on food allergy are inundated with issues such as inadequate sample size and absence of multiple testing correction. Few included replication analyses or population stratification measures. Studies addressing these limitations along with functional studies are therefore needed to unravel the mechanisms of action of the identified genes.

BACKGROUND: IgE-mediated egg allergy presents as one of the most common food allergies in children. Measurement of egg white specific IgE (sIgE) levels in serum or skin prick test has been shown to be a poor predictor of clinical allergy to raw egg white, and also to baked or cooked egg. Recent developments in component resolved diagnostic (CRD) technology have enabled us to improve the way in which we diagnose and predict peanut allergy by examining IgE specificity to individual peptides. OBJECTIVES: We aimed to investigate whether egg CRD could improve current methods to diagnose various egg allergy phenotypes as well as predict the development of tolerance to egg. METHODS: Using the HealthNuts cohort of food challenge-proven egg allergic and egg-sensitized and egg-tolerant, age-matched 12-month infants with longitudinal follow-up at 2 and 4 years (n = 451), we measured serum egg white, Gal d 1, 2, 3 and 5 sIgE using ImmunoCAP. RESULTS: Gal d 1 sensitization increased the risk of persistent egg allergy by 2.5-fold. The production of sIgE to all four egg allergens (Gal d 1, 2, 3 or 5) increased the risk of having persistent raw egg allergy fourfold (OR 4.19 (95% CI: 1.25-14.07). We did not find any improvements of using Gal d 1, 2, 3 or 5 to diagnose current egg allergy compared to egg white sIgE. CONCLUSION: Sensitization to multiple egg allergens Gal d 1, 2, 3 or 5 may be a prognostic marker that could be useful for patient management and identifying individuals at risk of developing persistent egg allergy.

INTRODUCTION: BCG vaccination reduces all-cause infant mortality in high-mortality settings by more than can be attributed to protection against tuberculosis. This is proposed to result from non-specific protection against non-vaccine targeted ('off-target') infections. There is also evidence that BCG protects against allergic diseases. METHODS AND ANALYSIS: The Melbourne Infant Study: BCG for Allergy and Infection Reduction is a phase III multicentre, single-blinded, randomised controlled trial. A total of 1438 healthy neonates will be randomised to receive either BCG vaccination or no BCG vaccination in the first 10 days of life. Measures of allergy, eczema, infection and asthma will be obtained from parent-completed questionnaires 3 monthly in the first year and 6 monthly from 1 to 5 years of age, and clinical assessments at 1 and 5 years of age. Biological samples will also be collected for future immunological studies. ANALYSIS PRIMARY OUTCOME: The proportion of participants with measures of allergy and infection (atopic sensitisation, eczema, lower respiratory tract infection) at 1 and 5 years of age, and asthma at 5 years of age. SECONDARY OUTCOMES: (1) the proportion of participants with additional measures of allergy, eczema, asthma and infections; (2) medication use for eczema and asthma; (3) the severity and age of onset of eczema and asthma; (4) the number of episodes of infection; (5) hospitalisations for infections and (6) laboratory measures of immune responses. ETHICS AND DISSEMINATION: This trial has ethical and governance approval from Mercy Health Human Research Ethics Committee (HREC, No. R12-28) and Royal Children's Hospital HREC (No. 33025) with additional governance approval from Barwon Health and St John of God, Geelong, Victoria. Results of this trial will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT01906853.

BACKGROUND: Asthma and allergic diseases are heterogeneous. Measurement of biomarkers in exhaled breath condensate (EBC) may help to discriminate between different phenotypes and may assist with clinical prognostication. OBJECTIVES: We aimed to assess associations between total nitric oxide products (NOx ) in EBC and different allergic phenotypes and lung function in young and middle-aged adults. METHODS: Cross-sectional analyses were nested within two Australian longitudinal studies, the Melbourne Atopy Cohort Study (MACS, mean age 17.8 years) and the Tasmanian Longitudinal Health Study (TAHS, mean age 49.4 years). Levels of EBC NOx were determined by Griess-reaction fluorescent method. Associations were assessed between EBC NOx and different allergic phenotypes, lung function and airway reactivity. RESULTS: Atopy, with or without asthma or rhinitis, was associated with increased EBC NOx levels particularly in individuals with poly-aero-sensitization. These findings were generally consistent across the two age groups. In the older cohort, use of ICS in the previous 12 months masked the association between sensitization and EBC NOx (OR = 0.64, 95% CI = 0.21-1.96, p for interaction = 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: In these population-based samples, EBC NOx was most strongly associated with atopic sensitization, rather than either current asthma or rhinitis, possibly indicating underlying increased airway inflammation associated with atopy. Therefore, EBC NOx could be a key predictor of atopy in both young and middle-aged adults, regardless of the presence of concomitant asthma or rhinitis.

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.

Homozygosity for the p.C282Y substitution in the HFE protein encoded by the hemochromatosis gene on chromosome 6p (HFE) is a common genetic trait that increases susceptibility to iron overload. McLaren et al. used bivariate mixture modeling to analyze the joint population distribution of transferrin saturation (TS) and serum ferritin concentration (SF) measured for participants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. They identified four components (C1, C2, C3, and C4) with successively increasing means for TS and SF. They demonstrated that bivariate mixture modeling in TS and SF reflect the genetic locus of HFE and may isolate p.C282Y homozygotes from the general population. In the current study we used data from the another large cohort, the Australian HealthIron study of genetic and environmental modifiers of hereditary hemochromatosis, to validate the component analysis approach, to examine stability of component proportions over time and to determine if TS and SF values from an individual move between components at baseline and follow-up. Because sampling fractions from each p.C282Y / p.H63D genotype stratum are not equal, we used frequency weights based on the inverse of the probability of selection for invitation to participate. In the weighted female analytic cohorts, C4 captured most of C282Y homozygotes, and C2 was the largest component. We identified four components from the weighted male analytic cohort and C4 captured most of p.C282Y homozygotes. The bivariate mixture modeling approach suggested that the model is transferable from one white population to another, although estimated means within components may differ.

BACKGROUND: In previous studies, deficits in regulatory T-cell (Treg) number and function at birth have been linked with subsequent allergic disease. However, longitudinal studies that account for relevant perinatal factors are required. The aim of this study was to investigate the relationship between perinatal factors, naïve Treg (nTreg) over the first postnatal year and development of food allergy. METHODS: In a birth cohort (n = 1074), the proportion of nTreg in the CD4+ T-cell compartment was measured by flow cytometry at birth (n = 463), 6 (n = 600) and 12 (n = 675) months. IgE-mediated food allergy was determined by food challenge at 1 year. Associations between perinatal factors (gestation, labour, sex, birth size), nTreg at each time point and food allergy at 1 year were examined by linear regression. RESULTS: A higher proportion of nTreg at birth, larger birth size and male sex was each associated with higher nTreg in infancy. Exposure to labour, as compared to delivery by prelabour Caesarean section, was associated with a transient decrease nTreg. Infants that developed food allergy had decreased nTreg at birth, and the labour-associated decrease in nTreg at birth was more evident among infants with subsequent food allergy. Mode of birth was not associated with risk of food allergy, and there was no evidence that nTreg at either 6 or 12 months were related to food allergy. CONCLUSION: The proportion of nTreg at birth is a major determinant of the proportion present throughout infancy, highlighting the importance of prenatal immune development. Exposure to the inflammatory stimulus of labour appears to reveal differences in immune function among infants at risk of food allergy.

BACKGROUND: Markers of microbial exposure are thought to be associated with risk of allergic sensitization; however, the associations are inconsistent and may be related to gene-environment interactions. OBJECTIVE: To examine the relationship between polymorphisms in the CD14 gene and allergic sensitization and whether sibling exposure, as a marker of microbial exposure, modified this relationship. METHODS: We used data from the Tasmanian Longitudinal Health Study and the Melbourne Atopy Cohort Study. Two CD14 polymorphisms were genotyped. Allergic sensitization was defined by a positive response to a skin prick test. Sibling exposure was measured as cumulative exposure to siblings before age 6 months, 2 and 4 years. Logistic regression and multi-level mixed-effects logistic regression were used to examine the associations. Effect estimates across the cohorts were pooled using random-effects meta-analysis. RESULTS: CD14 SNPs were not individually associated with allergic sensitization in either cohort. In TAHS, cumulative sibling exposure before age 6 months, 2 and 4 years was each associated with a reduced risk of allergic sensitization at age 45 years. A similar effect was observed in MACS. Meta-analysis across the two cohorts showed consistent evidence of an interaction between cumulative sibling exposure before 6 months and the rs5744455-SNP (P = 0.001) but not with the rs2569190-SNP (P = 0.60). The pooled meta-analysis showed that the odds of sensitization with increasing cumulative exposure to sibling before 6 months of age was 20.9% smaller in those with the rs5744455-C-allele than the T-allele (OR = 0.83 vs 1.05, respectively). CONCLUSION AND CLINICAL RELEVANCE: Cumulative sibling exposure reduced the risk of sensitization from childhood to middle age in genetically susceptible individuals.

The ecology of the Australian monsoon tropics is fundamentally shaped by dry conditions between May and October followed by highly variable rainfall over the months of November to April. Due to its crucial ecological importance, a better understanding of past hydroclimate variability in the region is of great interest to land managers and custodians in this region. Short instrumental records also make highly resolved terrestrial palaeoclimate records for northern Australia prior to 1900 CE of considerable scientific importance. Here, we present two new well‐replicated Callitris intratropica ring‐width chronologies from Arnhem Land in northern Australia, one of which extends the tree‐ring record in the region by another 86 years, back to 1761. Both chronologies have clearly defined regional patterns of correlations with temperature, precipitation, potential evapotranspiration and two drought indices (the self‐calibrating Palmer Drought Severity Index (PDSI) and the Standardised Precipitation Evapotranspiration Index (SPEI)) across the lower latitudes of the Northern Territory. Results indicate considerable scope for hydroclimatic reconstructions based on C. intratropica for transitional periods into and out of the wettest time of the year. This suggests that such reconstructions would reflect variability in the duration of the wet period. While precipitation or streamflow reconstructions may be possible for both these transitional periods, drought reconstructions will be best focused on the months of March–May at the end of the wet period. Hydroclimate reconstructions would provide important baseline information for understanding the rate and magnitude of current regional climate change for these ecologically and culturally important transitional periods.

Environmental Research Letters, 13 (2018) 1–10. doi: 10.1088/1748-9326/aaafd7

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.

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 b

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 FEV1 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, ac

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 warran

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.

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.

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.

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.

Temporal stability of the relationship between a potential proxy climate record and the climate record itself is the foundation of palaeoproxy reconstructions of past climate variability. Dendroclimatologists have spent considerable effort exploring the issue of temporal instability of temperature records at high-latitude and −altitude Northern Hemisphere sites. Much of this work has focused on the Divergence Problem in which the modern ends of tree-ring chronologies exhibit pronounced departures from the climate-proxy relationships of preceding decades. However, there has been little scrutiny of how different methods might influence determinations of temporal instability at either the local scale or across broader spatial domains. Here we use four sets of Southern Hemisphere (SH) chronologies and three sets of synthetic data with known interventions to compare four methodologies that have been widely used to assess the temporal stability of relationships between tree-ring series and climate. Our analyses demonstrate that a determination of temporal instability may be partially dependent on method used to examine data, that some methods are more sensitive to standardisation choice than others, and that all methods are better at detecting high- rather than low-frequency instability. In all cases, the relatively modest strength of the relationships between the selected SH ring-width chronologies and temperature is likely to be an issue, especially if changes in trends are of interest. We recommend that robust assessment of temporal instability between tree-ring chronologies and observational climate data should use a range of methods and that unstable temporal relationships across space be carefully considered in the context of large climate field reconstructions.

Temporal stability of the relationship between a potential proxy climate record and the climate record itself is the foundation of palaeoproxy reconstructions of past climate variability. Dendroclimatologists have spent considerable effort exploring the issue of temporal instability of temperature records at high-latitude and −altitude Northern Hemisphere sites. Much of this work has focused on the Divergence Problem in which the modern ends of tree-ring chronologies exhibit pronounced departures from the climate-proxy relationships of preceding decades. However, there has been little scrutiny of how different methods might influence determinations of temporal instability at either the local scale or across broader spatial domains. Here we use four sets of Southern Hemisphere (SH) chronologies and three sets of synthetic data with known interventions to compare four methodologies that have been widely used to assess the temporal stability of relationships between tree-ring series and climate. Our analyses demonstrate that a determination of temporal instability may be partially dependent on method used to examine data, that some methods are more sensitive to standardisation choice than others, and that all methods are better at detecting high- rather than low-frequency instability. In all cases, the relatively modest strength of the relationships between the selected SH ring-width chronologies and temperature is likely to be an issue, especially if changes in trends are of interest. We recommend that robust assessment of temporal instability between tree-ring chronologies and observational climate data should use a range of methods and that unstable temporal relationships across space be carefully considered in the context of large climate field reconstructions.

© 2017 Acta Dermato-Venereologica. 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.

Australian seasonal rainfall is strongly affected by large-scale ocean–atmosphere climate influences. In this study, we exploit the links between these precipitation influences, regional rainfall variations, and palaeoclimate proxies in the region to reconstruct Australian regional rainfall between four and eight centuries into the past. We use an extensive network of palaeoclimate records from the Southern Hemisphere to reconstruct cool (April–September) and warm (October–March) season rainfall in eight natural resource management (NRM) regions spanning the Australian continent. Our bi-seasonal rainfall reconstruction aligns well with independent early documentary sources and existing reconstructions. Critically, this reconstruction allows us, for the first time, to place recent observations at a bi-seasonal temporal resolution into a pre-instrumental context, across the entire continent of Australia. We find that recent 30- and 50-year trends towards wetter conditions in tropical northern Australia are highly unusual in the multi-century context of our reconstruction. Recent cool-season drying trends in parts of southern Australia are very unusual, although not unprecedented, across the multi-century context. We also use our reconstruction to investigate the spatial and temporal extent of historical drought events. Our reconstruction reveals that the spatial extent and duration of the Millennium Drought (1997–2009) appears either very much below average or unprecedented in southern Australia over at least the last 400 years. Our reconstruction identifies a number of severe droughts over the past several centuries that vary widely in their spatial footprint, highlighting the high degree of diversity in historical droughts across the Australian continent. We document distinct characteristics of major droughts in terms of their spatial extent, duration, intensity, and seasonality. Compared to the three largest droughts in the instrumental period (Federation

Seasonal variability is a significant source of uncertainty in projected changes to precipitation across southeastern Australia (SEA). While existing instrumental records provide seasonal data for recent decades, most proxy records (e.g., tree rings, corals, speleothems) offer only annual reconstructions of hydroclimate. We present the first cool‐season (July–August) reconstruction of dam inflow (Lake Burbury) for western Tasmania in SEA based on tree‐ring width (Athrotaxis selaginoides) and mean latewood cell wall thickness (Phyllocladus aspleniifolius) chronologies. The reconstruction, produced using principal component regression, verifies back to 1731 and is moderately skillful, explaining around 23% of the variance. According to the reconstruction, relatively low inflow periods occurred around 1860, the early 1900s and 1970, while relatively high inflows occurred in the 1770s and 1810s. Highest reconstructed inflows occurred in 1816, and lowest in 1909. Comparison with available documentary and instrumental records indicates that the reconstruction better captures high rather than low flow events. There is virtually no correlation between our reconstruction and another for December–January inflow for the same catchment, a result consistent with the relationship between seasonal instrumental data. This suggests that conditions in one season have not generally reflected conditions in the other season over the instrumental record, or for the past 277 years. This illustrates the value of obtaining reconstructions of regional hydroclimatic variability for multiple individual seasons in regions where dry and wet seasons are not strongly defined. The results also indicate that the hydroclimate of the southeastern Australian region cannot be adequately represented by a single regional reconstruction.

BACKGROUND: The precautionary allergen labelling (PAL) and Voluntary Incidental Trace Allergen Labelling (VITAL® ) tools were designed by industry to assist consumers with selecting safe foods for consumption. However, a sizeable proportion of food products bear no label, and it is unclear whether these products are free from allergens and therefore safe to consume or have simply not undergone a risk assessment and therefore remain unlabelled for that reason. OBJECTIVE: To assess the prevalence of unlabelled products that have undergone a risk assessment process and to examine the factors influencing industry's uptake of the VITAL® process. METHODS: A web-based questionnaire was distributed to Australasian food and grocery manufacturers. RESULTS: One hundred and thirty-seven Australasian manufacturers were contacted, and 59 questionnaires were returned (response rate: 43%). The respondents represented 454 different manufacturing sites. Manufacturers reported that 23% (95% CI 19-28) of products (n=102/434) that had been through the VITAL® risk assessment process had no PAL statement on the label. 34% (95% CI 30-38), (n=204/600) of products that had undergone another (non-VITAL® ) risk assessment process had no PAL statement. In examining the factors that influenced industry's uptake of the VITAL® process, 25 manufacturers reported on factors that influenced the uptake of the VITAL® process, 76% (CI 95% 55-91) reported that VITAL® was an effective tool because it was based on science; 52% (CI 95% 31-72) reported that it was too time-consuming and 36% (CI 95% 18-57) identified a concern with it not being endorsed by the government. CONCLUSION AND CLINICAL RELEVANCE: Currently, we estimate that at least 30% of products may have been through a risk assessment process and yet bear no PAL statement on the label. Permissive labelling could be incorporated onto these products if they have been assessed to be safe for consumption.

Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high- and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python.