Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and >100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma susceptibility genes. We performed linkage and association analyses by transmission/disequilibrium test and case-control analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including inactivating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF- kappa B and inflammation. Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflammation and indicate IRAK-M as a potential target for therapeutic intervention against asthma.

Our results show that the prevalence of asthma increases when annual mean temperature increases and temperature range decreases. Furthermore, climate interacts with NO2 outdoor exposure, increasing the risk for allergic rhinitis in people exposed to high stable temperatures. A long-term role for the effect of traffic pollution on asthma is also suggested.

Despite the high percentage of drug users, the control of symptoms and exacerbations was overall poor in Italy and resulted in a heavy individual and social burden, pointing out that the guideline goals have far from been reached in Italy.

For more than a century, the contact between wheel and rail has been the subject of careful investigation by scientists and railway technicians. Many efforts have been made to understand a series of phenomena (wear, pitting, fatigue, failures, etc.) that are closely related to processes occurring in such a small contact patch. A huge amount of numerical and theoretical research work (starting from Hertz's theory) has been carried out, but there is a noteworthy lack of experimental tests, which is probably due mainly to difficulties in accessing the contact area with conventional techniques. In the present paper, an experimental investigation dealing with the evaluation of the contact area and stresses transmitted across it is proposed: the technique employed is based on a noninvasive ultrasonic method that analyses the reflection of ultrasonic waves by the contact interface. By using a set-up commonly employed in many non-destructive testing (NDT) analyses it was possible to obtain graphic maps of static contact conditions, and several tests were carried out to evaluate changes with increases in external load. Results show reasonable agreement with Hertz's theoretical predictions and suggest a possible future use of the ultrasonic method to investigate contact during motion

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