Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1

<p>Abstract</p> <p>Background</p> <p>Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children.</p> <p>Methods</p> <p>In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2) were associated with eczema. We tested these SNPs for interaction with early life endotoxin exposure (n = 291), in models for asthma and eczema by age 6.</p> <p>Results</p> <p>We found a significant interaction between endotoxin and a SNP (rs156265) in ACAA1 (p = 0.0013 for interaction). Increased endotoxin exposure (by quartile) showed protective effects for asthma in individuals with at least one copy of the minor allele (OR = 0.39 per quartile increase in endotoxin, 95% CI 0.15 to 1.01). Endotoxin exposure did not reduce the risk of asthma in children homozygous for the major allele.</p> <p>Conclusion</p> <p>Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1.</p

Metastable Vacua in Flux Compactifications and Their Phenomenology

In the context of flux compactifications, metastable vacua with a small positive cosmological constant are obtained by combining a sector where supersymmetry is broken dynamically with the sector responsible for moduli stabilization, which is known as the F-uplifting. We analyze this procedure in a model-independent way and study phenomenological properties of the resulting vacua.Comment: 21 pages, 19 figures; v2: matches version published in JHE

How low can SUSY go? Matching, monojets and compressed spectra

If supersymmetry (SUSY) has a compressed spectrum then the current mass limits from the LHC can be drastically reduced. We consider a possible 'worst case' scenario where the gluino and/or squarks are degenerate with the lightest SUSY particle (LSP). The most sensitive searches for these compressed spectra are via the final state LSPs recoiling against initial state radiation (ISR). Therefore it is vital that the ISR is understood and possible uncertainties in the predictions are evaluated. We use both MLM (with Pythia 6) and CKKW- L (with Pythia 8) matching and vary matching scales and parton shower properties to accurately determine the theoretical uncertainties in the kinematic distributions. All current LHC SUSY and monojet analyses are employed and we find the most constraining limits come from the CMS Razor and CMS monojet searches. For a scenario of squarks degenerate with the LSP and decoupled gluinos we find $M_{\tilde{q}}>340$ GeV. For gluinos degenerate with the LSP and decoupled squarks, $M_{\tilde{g}}>500$ GeV. For equal mass squarks and gluinos degenerate with the LSP, $M_{\tilde{q},\tilde{g}}>650$ GeV.Comment: References added, version submitted to ep

Effects of Pore Walls and Randomness on Phase Transitions in Porous Media

We study spin models within the mean field approximation to elucidate the topology of the phase diagrams of systems modeling the liquid-vapor transition and the separation of He$^3$--He$^4$ mixtures in periodic porous media. These topologies are found to be identical to those of the corresponding random field and random anisotropy spin systems with a bimodal distribution of the randomness. Our results suggest that the presence of walls (periodic or otherwise) are a key factor determining the nature of the phase diagram in porous media.Comment: REVTeX, 11 eps figures, to appear in Phys. Rev.

Respiratory symptoms among infants at risk for asthma: association with surfactant protein A haplotypes

BACKGROUND: We examined the association between single nucleotide polymorphisms (SNPs) in loci encoding surfactant protein A (SFTPA) and risk of wheeze and persistent cough during the first year of life among a cohort of infants at risk for developing asthma. METHODS: Between September 1996 and December 1998, mothers of newborn infants were invited to participate if they had an older child with clinician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Due to the association of SFTPA polymorphisms and race/ethnicity, analyses were restricted to 221 white infants for whom whole blood and respiratory data were available. Ordered logistic regression models were used to examine the association between respiratory symptom frequency and SFTPA haplotypes. RESULTS: The 6A allele haplotype of SFTPA1, with an estimated frequency of 6% among our study infants, was associated with an increased risk of persistent cough (OR 3.69, 95% CI 1.71, 7.98) and wheeze (OR 4.72, 95% CI 2.20, 10.11). The 6A/1A haplotype of SFTPA, found among approximately 5% of the infants, was associated with an increased risk of persistent cough (OR 3.20, 95% CI 1.39, 7.36) and wheeze (OR 3.25, 95% CI 1.43, 7.37). CONCLUSION: Polymorphisms within SFTPA loci may be associated with wheeze and persistent cough in white infants at risk for asthma. These associations require replication and exploration in other ethnic/racial groups