Infant and early childhood dietary predictors of overweight at age 8 years in the CAPS population

BACKGROUND/OBJECTIVES: Programs to address obesity are a high priority for public policy especially for young children. Research into dietary determinants of obesity is challenging but important for rational planning of interventions to prevent obesity, given that both diet and energy expenditure influence weight status. We investigated whether early life dietary factors were predictive of weight status at 8 years in a cohort of Australian children. SUBJECTS/METHODS: We used data from the Childhood Asthma Prevention Study-a birth cohort at high risk of asthma. Dietary data (3-day weighed food records) were collected at 18 months and height, weight and waist circumference were collected at 8 years. We assessed the relationship between dietary predictor variables and measures of adiposity using linear regression. RESULTS: Intakes of protein, meat and fruit at age 18 months were positively associated with measures of adiposity at age 8 years, namely, body mass index and/or waist circumference. We also showed a significant negative relationship between these measures of adiposity at 8 years and intake at 18 months of dairy foods as a percent of total energy, and intake of energy dense cereal-based foods such as cookies and crackers. CONCLUSIONS: This birth cohort study with rigorous design, measures and analyses, has shown a number of associations between early dietary intake and subsequent adiposity that contribute to the growing evidence base in this important field.National Health and Medical Research Council of AustraliaHjärt- och LungfondenSvenska LäkarsällskapetManuscrip

Gene-Environment Interaction in the Onset of Eczema in Infancy: Filaggrin Loss-of-Function Mutations Enhanced by Neonatal Cat Exposure

Background Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema. Methods and Findings We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen(n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27–4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79–32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24–1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13–3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35–10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16–2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation. Conclusions We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life

Developments in the field of allergy in 2017 through the eyes of Clinical and Experimental Allergy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146621/1/cea13318.pd

Developments in the field of clinical allergy in 2018 through the eyes of Clinical and Experimental Allergy, Part II

In this article, we describe developments in the field of clinical allergy as described by Clinical and Experimental Allergy in 2018; epidemiology, asthma and rhinitis, clinical allergy and allergens are all covered.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153257/1/cea13535.pd

Breastfeeding, asthma, and allergy : a tale of two cities

BACKGROUND: The effect of breastfeeding duration on subsequent asthma and allergy remains the subject of much controversy. OBJECTIVE: To investigate whether differences in study design or disease-related exposure modification were the cause of the differences in study findings. METHOD: The data from two cohorts, the Childhood Asthma Prevention Study (CAPS) from Australia and the Barn Allergi Miljo Stockholm cohort from Sweden, which had reported different findings on the association between breastfeeding and asthma, were combined. For this analysis, the definitions for breastfeeding, asthma, and allergy were harmonized. Subjects were included if they had at least one parent with wheeze or asthma and had a gestational age of more than 36 wks (combined n = 882). The risk of disease-related exposure modification was assessed using survival analysis. RESULTS: Breastfeeding reduced the risk of asthma at 4/5 and 8 yrs of age in children with a family history of asthma. The effect was stronger in the Swedish cohort. Breastfeeding had no effect on the prevalence of sensitization to inhaled allergens in this cohort with a family history of asthma but was a risk factor for sensitization to cow's milk, peanuts, and eggs in the CAPS cohort at 4/5 yrs and in the combined cohort at 8 yrs. There was no evidence to support the existence of disease-related exposure modification in either cohort. CONCLUSION: These findings point to the importance of harmonization of features of study design, including subject selection criteria and variable definitions, in resolving epidemiological controversies such as those surrounding the impact of breastfeeding on asthma and allergic sensitization.National Health and Medical Research Council of AustraliaStockholm County CouncilHjärt- och LungfondenThe Swedish Asthma and Allergy AssociationVetenskapsrådetThe Centre for Allergy research Karolinska InstitutetManuscrip

A Multi-Phase Transport model for nuclear collisions at RHIC

To study heavy ion collisions at energies available from the Relativistic Heavy Ion Collider, we have developed a multi-phase transport model that includes both initial partonic and final hadronic interactions. Specifically, the parton cascade model ZPC, which uses as input the parton distribution from the HIJING model, is extended to include the quark-gluon to hadronic matter transition and also final-state hadronic interactions based on the ART model. Predictions of the model for central Au on Au collisions at RHIC are reported.Comment: 7 pages, 4 figure

Using fathers as a negative control exposure to test the developmental origins of health and disease hypothesis : a case study on maternal distress and offspring asthma using Swedish register data

Background: Developmental Origins of Health and Disease Hypothesis (DOHaD) studies are often observational in nature and are therefore prone to biases from loss to follow-up and unmeasured confounding. Register-based studies can reduce these issues since they allow almost complete follow-up and provide information on fathers that can be used in a negative control analysis to assess the impact of unmeasured confounding. Aim: To propose a causal model for testing DOHaD using paternal exposure as a negative control, and its application to maternal distress in pregnancy and offspring asthma. Methods: A causal diagram including shared and parent-specific measured and unmeasured confounders for maternal (fetal) and paternal exposures is proposed. The case-study consisted of all children born in Sweden from July 2006 to December 2008 (n=254 150). Information about childhood asthma, parental distress and covariates was obtained from the Swedish National health registers. Associations between maternal and paternal distress during pregnancy and offspring asthma at age 5 years were assessed separately and with mutual adjustment for the other parent’s distress measure, as well as for shared confounders. Results: Maternal distress during pregnancy was associated with offspring asthma risk; mutually adjusted Odds Ratio (OR) 1.32 (95% CI 1.23, 1.43). The mutually adjusted paternal distress-offspring asthma analysis (OR 1.05 95% CI 0.97, 1.13) indicated no evidence for unmeasured confounding shared by the mother and father. Conclusions: Using paternal exposure in a negative control model to test the robustness of fetal programming hypotheses can be a relatively simple extension of conventional observational studies but limitations need to be considered.NoneManuscrip

Randomized assessment of imatinib in patients with acute ischaemic stroke treated with intravenous thrombolysis

BackgroundImatinib, a tyrosine kinase inhibitor, has been shown to restore bloodâ brain barrier integrity and reduce infarct size, haemorrhagic transformation and cerebral oedema in stroke models treated with tissue plasminogen activator. We evaluated the safety of imatinib, based on clinical and neuroradiological data, and its potential influence on neurological and functional outcomes.MethodsA phase II randomized trial was performed in patients with acute ischaemic stroke treated with intravenous thrombolysis. A total of 60 patients were randomly assigned to four groups [3 (active): 1 (control)]; the active treatment groups received oral imatinib for 6 days at three dose levels (400, 600 and 800 mg). Primary outcome was any adverse event; secondary outcomes were haemorrhagic transformation, cerebral oedema, neurological severity on the National Institutes of Health Stroke Scale (NIHSS) at 7 days and at 3 months and functional outcomes on the modified Rankin scale (mRS).ResultsFour serious adverse events were reported, which resulted in three deaths (one in the control group and two in the 400â mg dose group; one patient in the latter group did not receive active treatment and the other received two doses). Nonserious adverse events were mostly mild, resulting in full recovery. Imatinib ameliorated neurological outcomes with an improvement of 0.6 NIHSS points per 100 mg imatinib (P = 0.02). For the 800â mg group, the mean unadjusted and adjusted NIHSS improvements were 4 (P = 0.037) and 5 points (P = 0.012), respectively, versus controls. Functional independence (mRS 0â 2) increased by 18% versus controls (61 vs. 79; P = 0.296).ConclusionThis phase II study showed that imatinib is safe and tolerable and may reduce neurological disability in patients treated with intravenous thrombolysis after ischaemic stroke. A confirmatory randomized trial is currently underway.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136298/1/joim12576_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136298/2/joim12576.pd