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- Bousquet, J, et al.
(author)
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Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper
- 2012
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In: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 158:3, s. 216-231
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Journal article (peer-reviewed)abstract
- Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.
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- Cerhan, James R., et al.
(author)
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Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma
- 2014
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:11, s. 1233-1238
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Journal article (peer-reviewed)abstract
- Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 x 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 x 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 x 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 x 10(-13) and 3.63 x 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
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- Wormser, David, et al.
(author)
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Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
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Journal article (peer-reviewed)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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- Tyrrell, Jessica, et al.
(author)
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Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight.
- 2012
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In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 21:24, s. 5344-5358
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Journal article (peer-reviewed)abstract
- Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P = 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P = 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: -4to 14 g; P = 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.
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- Liseau, René, 1949, et al.
(author)
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Multi-line detection of O2 toward rho Ophiuchi A
- 2012
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541
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Journal article (peer-reviewed)abstract
- Context. Models of pure gas-phase chemistry in well-shielded regions of molecular clouds predict relatively high levels of molecular oxygen, O-2, and water, H2O. These high abundances imply high cooling rates, leading to relatively short timescales for the evolution of gravitationally unstable dense cores, forming stars and planets. Contrary to expectations, the dedicated space missions SWAS and Odin typically found only very small amounts of water vapour and essentially no O-2 in the dense star-forming interstellar medium. Aims. Only toward rho OphA did Odin detect a very weak line of O-2 at 119 GHz in a beam of size 10 arcmin. The line emission of related molecules changes on angular scales of the order of some tens of arcseconds, requiring a larger telescope aperture such as that of the Herschel Space Observatory to resolve the O-2 emission and pinpoint its origin. Methods. We use the Heterodyne Instrument for the Far Infrared (HIFI) aboard Herschel to obtain high resolution O-2 spectra toward selected positions in the rho Oph A core. These data are analysed using standard techniques for O2 excitation and compared to recent PDR-like chemical cloud models. Results. The N-J = 3(3)-1(2) line at 487.2 GHz is clearly detected toward all three observed positions in the rho Oph A core. In addition, an oversampled map of the 5(4)-3(4) transition at 773.8 GHz reveals the detection of the line in only half of the observed area. On the basis of their ratios, the temperature of the O-2 emitting gas appears to vary quite substantially, with warm gas (greater than or similar to 50 K) being adjacent to a much colder region, of temperatures lower than 30 K. Conclusions. The exploited models predict that the O-2 column densities are sensitive to the prevailing dust temperatures, but rather insensitive to the temperatures of the gas. In agreement with these models, the observationally determined O-2 column densities do not seem to depend strongly on the derived gas temperatures, but fall into the range N(O-2) = 3 to greater than or similar to 6 x 10(15) cm(-2). Beam-averaged O-2 abundances are about 5 x 10(-8) relative to H-2. Combining the HIFI data with earlier Odin observations yields a source size at 119 GHz in the range of 4 to 5 arcmin, encompassing the entire rho Oph A core. We speculate that one of the reasons for the generally very low detection rate of O-2 is the short period of time during which O-2 molecules are reasonably abundant in molecular clouds.
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- Gifstad, T, et al.
(author)
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Lower risk of revision with patellar tendon autografts compared with hamstring autografts: a registry study based on 45,998 primary ACL reconstructions in Scandinavia
- 2014
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In: The American journal of sports medicine. - : SAGE Publications. - 1552-3365 .- 0363-5465. ; 42:10, s. 2319-2328
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Journal article (peer-reviewed)abstract
- A number of studies have found comparable results after anterior cruciate ligament (ACL) reconstruction with patellar tendon autografts and hamstring autografts; however, few studies have been large enough to reveal differences in risk of revision with regard to clinical and demographic factors. Purpose: To present the distribution of grafts for ACL reconstruction based on data in the Scandinavian ACL registries and to compare the risk of revision between patellar tendon autografts and hamstring autografts. Potential associations with other clinical and demographic factors were also explored. Study design: Cohort study; Level of evidence, 2. Methods: A total of 45,998 primary ACL reconstructions, including 6736 patellar tendon autografts and 38,666 hamstring autografts, were identified in the Scandinavian ACL registries. The overall median follow-up time was 3 years (range, 0-8 years). To compare the risk of revision between groups of patients, univariate Kaplan-Meier analysis (with log-rank test) and the Cox proportional hazard regression model were applied. The hazard rate ratio with 95% CI was reported as a measure of effect. Results: Patellar tendon and hamstring autografts were used in 14.6% and 84.1% of the patients, respectively. The remaining patients received allografts, direct sutures, or other graft types (1.3%). The primary ACL injury occurred during soccer, team handball, or alpine activities in 67.5% of the patients in the patellar tendon group and 66.2% in the hamstring group. A total of 156 patients in the patellar tendon group and 1042 patients in the hamstring group underwent revision. The overall risk of revision was significantly lower in the patellar tendon group versus the hamstring group (hazard rate ratio = 0.63; 95% CI, 0.53-0.74), and it decreased with increasing age at surgery, although not strictly linearly. The lower risk of revision in the patellar tendon group was consistently observed across subgroups of patient sex, age, and concomitant cartilage injury ( P > .05, test for interaction) but seemed to be slightly more pronounced for patients injured during certain pivoting activities (soccer, team handball, and alpine activities) compared with other activities (hazard rate ratio = 0.57 vs 0.81; P = .058, test for interaction). Conclusion: The majority of primary ACL reconstructions in Scandinavia are performed with hamstring autografts. Results from the present large prospective study show that patients receiving patellar tendon autografts have a statistically significantly lower risk of revision compared with patients receiving hamstring autografts.
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- Kim, K, et al.
(author)
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Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries
- 2012
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 71:11, s. 1809-1814
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin αM (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM.MethodsThe authors examined several markers in the ICAM1–ICAM4–ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case–control study of 17 481 unrelated participants from four ancestry populations. The single-marker association and gene–gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed.ResultsThe A-allele of ICAM1–ICAM4–ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (ORmeta=1.16, 95% CI 1.11 to 1.22; p=4.88×10−10 and ORmeta=1.67, 95% CI 1.55 to 1.79; p=3.32×10−46, respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10−5).ConclusionThese findings are the first to suggest that an ICAM–integrin-mediated pathway contributes to susceptibility to SLE.
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- Koushik, Anita, et al.
(author)
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Intake of fruits and vegetables and risk of pancreatic cancer in a pooled analysis of 14 cohort studies
- 2012
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 176:5, s. 373-386
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Journal article (peer-reviewed)abstract
- Fruit and vegetable intake may protect against pancreatic cancer, since fruits and vegetables are rich in potentially cancer-preventive nutrients. Most case-control studies have found inverse associations between fruit and vegetable intake and pancreatic cancer risk, although bias due to reporting error cannot be ruled out. In most prospective studies, inverse associations have been weaker and imprecise because of small numbers of cases. The authors examined fruit and vegetable intake in relation to pancreatic cancer risk in a pooled analysis of 14 prospective studies from North America, Europe, and Australia (study periods between 1980 and 2005). Relative risks and 2-sided 95% confidence intervals were estimated separately for the 14 studies using the Cox proportional hazards model and were then pooled using a random-effects model. Of 862,584 men and women followed for 7-20 years, 2,212 developed pancreatic cancer. The pooled multivariate relative risks of pancreatic cancer per 100-g/day increase in intake were 1.01 (95% confidence interval (CI): 0.99, 1.03) for total fruits and vegetables, 1.01 (95% CI: 0.99, 1.03) for total fruits, and 1.02 (95% CI: 0.99, 1.06) for total vegetables. Associations were similar for men and women separately and across studies. These results suggest that fruit and vegetable intake during adulthood is not associated with a reduced pancreatic cancer risk.
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