The bisymplectomorphism group of a bounded symmetric domain

An Hermitian bounded symmetric domain in a complex vector space, given in its circled realization, is endowed with two natural symplectic forms: the flat form and the hyperbolic form. In a similar way, the ambient vector space is also endowed with two natural symplectic forms: the Fubini-Study form and the flat form. It has been shown in arXiv:math.DG/0603141 that there exists a diffeomorphism from the domain to the ambient vector space which puts in correspondence the above pair of forms. This phenomenon is called symplectic duality for Hermitian non compact symmetric spaces. In this article, we first give a different and simpler proof of this fact. Then, in order to measure the non uniqueness of this symplectic duality map, we determine the group of bisymplectomorphisms of a bounded symmetric domain, that is, the group of diffeomorphisms which preserve simultaneously the hyperbolic and the flat symplectic form. This group is the direct product of the compact Lie group of linear automorphisms with an infinite-dimensional Abelian group. This result appears as a kind of Schwarz lemma.Comment: 19 pages. Version 2: minor correction

Weighted Bergman kernels and virtual Bergman kernels

We introduce the notion of "virtual Bergman kernel" and apply it to the computation of the Bergman kernel of "domains inflated by Hermitian balls", in particular when the base domain is a bounded symmetric domain.Comment: 12 pages. One-hour lecture for graduate students, SCV 2004, August 2004, Beijing, P.R. China. V2: typo correcte

Prevalence and incidence of, and risk factors for chronic cough in the adult population : the Rotterdam Study

Chronic cough is a common complaint in the general population but there are no precise data on the incidence of, and prospectively examined risk factors for chronic cough in a population-based setting. Therefore, we investigated the period prevalence, incidence and risk factors for chronic cough in adult subjects. In a prospective population-based cohort study among subjects aged >= 45 years, data on chronic cough were collected on two separate occasions using a standardised questionnaire. Chronic cough was defined as daily coughing for at least 3 months duration during the preceding 2 years. Potential risk factors were gathered by interview, physical examination and several investigations. Of the 9824 participants in this study, 1073 (10.9%) subjects had chronic cough at baseline. The prevalence of chronic cough increased with age and peaked in the eighth decade. In subjects aged <70 years, chronic cough was more common in women. During an average follow-up of 6 years, 439 incident cases of chronic cough occurred with an overall incidence rate of 11.6 per 1000 person-years (95% CI 10.6-12.8). In current smokers, the incidence of chronic cough was higher in men. In the multivariable analysis, current smoking, gastro-oesophageal reflux disease (GORD), asthma and COPD were identified as risk factors for chronic cough. Chronic cough is common among adults and highly prevalent in the older population. Current smoking, GORD, asthma and COPD are independent risk factors for chronic cough. Individuals at risk of developing chronic cough may benefit from smoking cessation and control of the underlying disease

Are slaughterhouse-obtained livers suitable for use in ex vivo perfusion research?

Objectives: The success of the ex vivo machine perfusion of pig livers used for preclinical research depends on organ quality and availability. In this study, we investigated whether livers obtained from slaughterhouses are suitable and equivalent to livers obtained from laboratory pigs. Methods: Livers were obtained from slaughterhouse pigs stunned by electrocution or CO2 inhalation and from laboratory pigs. For the latter group, 45 minutes of warm ischemia was mimicked for a subgroup, ensuring a valid comparison with slaughterhouse-derived livers. Results: Livers from CO2-stunned pigs showed lower indocyanine green clearance and bile production, higher blood lactate and potassium concentrations, and higher alanine aminotransferase activities than electrically stunned pigs. Furthermore, livers from electrically stunned pigs, and livers from laboratory pigs, subjected or not to warm ischemia, showed similar performance in terms of perfusion and metabolism. Conclusion: For an ex vivo liver model generated using slaughterhouse pigs, electrical stunning is preferable to CO2 stunning. Livers from electrically stunned slaughterhouse pigs performed similarly to laboratory pig livers. These findings support the use of livers from electrically stunned slaughterhouse pigs, which may therefore provide an alternative to livers obtained from laboratory pigs, consistent with the principle of the 3Rs.</p

Pharmacogenetics of inhaled corticosteroids and exacerbation risk in adults with asthma

Background: Inhaled corticosteroids (ICS) are a cornerstone of asthma treatment. However, their efficacy is characterized by wide variability in individual responses. Objective: We investigated the association between genetic variants and risk of exacerbations in adults with asthma and how this association is affected by ICS treatment. Methods: We investigated the pharmacogenetic effect of 10 single nucleotide polymorphisms (SNPs) selected from the literature, including SNPs previously associated with response to ICS (assessed by change in lung function or exacerbations) and novel asthma risk alleles involved in inflammatory pathways, within all adults with asthma from the Dutch population-based Rotterdam study with replication in the American GERA cohort. The interaction effects of the SNPs with ICS on the incidence of asthma exacerbations were assessed using hurdle models adjusting for age, sex, BMI, smoking and treatment step according to the GINA guidelines. Haplotype analyses were also conducted for the SNPs located on the same chromosome. Results: rs242941 (CRHR1) homozygotes for the minor allele (A) showed a significant, replicated increased risk for frequent exacerbations (RR = 6.11, P < 0.005). In contrast, rs1134481T allele within TBXT (chromosome 6, member of a family associated with embryonic lung development) showed better response with ICS. rs37973 G allele (GLCCI1) showed a significantly poorer response on ICS within the discovery cohort, which was also significant but in the opposite direction in the replication cohort. Conclusion: rs242941 in CRHR1 was associated with poor ICS response. Conversely, TBXT variants were associated with improved ICS response. These associations may reveal specific endotypes, potentially allowing prediction of exacerbation risk and ICS response

Epigenomic partitioning of a polygenic risk score for asthma reveals distinct genetically driven disease pathways

Background Individual differences in susceptibility to developing asthma, a heterogeneous chronic inflammatory lung disease, are poorly understood. Whether genetics can predict asthma risk and how genetic variants modulate the complex pathophysiology of asthma are still debated. Aim To build polygenic risk scores for asthma risk prediction and epigenomically link predictive genetic variants to pathophysiological mechanisms. Methods Restricted polygenic risk scores were constructed using single nucleotide variants derived from genome-wide association studies and validated using data generated in the Rotterdam Study, a Dutch prospective cohort of 14 926 individuals. Outcomes used were asthma, childhood-onset asthma, adulthood-onset asthma, eosinophilic asthma and asthma exacerbations. Genome-wide chromatin analysis data from 19 disease-relevant cell types were used for epigenomic polygenic risk score partitioning. Results The polygenic risk scores obtained predicted asthma and related outcomes, with the strongest associations observed for childhood-onset asthma (2.55 odds ratios per polygenic risk score standard deviation, area under the curve of 0.760). Polygenic risk scores allowed for the classification of individuals into high-risk and low-risk groups. Polygenic risk score partitioning using epigenomic profiles identified five clusters of variants within putative gene regulatory regions linked to specific asthma-relevant cells, genes and biological pathways. Conclusions Polygenic risk scores were associated with asthma(-related traits) in a Dutch prospective cohort, with substantially higher predictive power observed for childhood-onset than adult-onset asthma. Importantly, polygenic risk score variants could be epigenomically partitioned into clusters of regulatory variants with different pathophysiological association patterns and effect estimates, which likely represent distinct genetically driven disease pathways. Our findings have potential implications for personalised risk mitigation and treatment strategies.</p