Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.

BACKGROUND: Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. METHODS: We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. RESULTS: First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03). CONCLUSIONS: Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma

Myocardial perfusion reserve compared with peripheral perfusion reserve: A [13N]ammonia PET study

INTRODUCTION: [13N]ammonia PET allows quantification of myocardial perfusion. The similarity between peripheral flow and myocardial perfusion is unclear. We compared perfusion flow in the myocardium with the upper limb during rest and adenosine stress [13N]ammonia PET to establish whether peripheral perfusion reserve (PPR) correlates with MPR. METHODS: [13N]ammonia myocardial perfusion PET-scans of 58 patients were evaluated (27 men, 31 women, age 64 ± 13 years) and were divided in four subgroups: patients with coronary artery disease (CAD, n = 15), cardiac syndrome X (SX, n = 14), idiopathic dilating cardiomyopathy (DCM, n = 16), and normal controls (NC, n = 13). Peripheral limb perfusion was measured in the muscular tissue of the proximal upper limb and quantified through a 2-tissue-compartment model and the PPR was calculated (stress/rest ratio). MPR was also calculated by a 2-tissue-compartment model. The PPR results were compared with the MPR findings. RESULTS: Mean myocardial perfusion increased significantly in all groups as evidenced by the MPR (CAD 1.99 ± 0.47; SX 1.39 ± 0.31; DCM 1.72 ± 0.69; NC 2.91 ± 0.78). Mean peripheral perfusion also increased but not significantly and accompanied with great variations within and between groups (mean PPR: CAD 1.30 ± 0.79; SX 1.36 ± 0.71; DCM 1.60 ± 1.22; NC 1.27 ± 0.63). The mean difference between PPR and MPR for all subpopulations varied widely. No significant correlations in flow reserve were found between peripheral and myocardial microcirculatory beds in any of the groups (Total group: r = -0.07, SEE = 0.70, CAD: r = 0.14, SEE = 0.48, SX: r = 0.17, SEE = 0.30, DCM: r = -0.11, SEE = 0.71, NC: r = -0.19, SEE = 0.80). CONCLUSION: No correlations between myocardial and peripheral perfusion (reserve) were found in different patient populations in the same PET session. This suggests a functional difference between peripheral and myocardial flow in the response to intravenously administered adenosine stress

Increased efficacy for in-house validation of real-time PCR GMO detection methods

To improve the efficacy of the in-house validation of GMO detection methods (DNA isolation and real-time PCR, polymerase chain reaction), a study was performed to gain insight in the contribution of the different steps of the GMO detection method to the repeatability and in-house reproducibility. In the present study, 19 methods for (GM) soy, maize canola and potato were validated in-house of which 14 on the basis of an 8-day validation scheme using eight different samples and five on the basis of a more concise validation protocol. In this way, data was obtained with respect to the detection limit, accuracy and precision. Also, decision limits were calculated for declaring non-conformance (>0.9%) with 95% reliability. In order to estimate the contribution of the different steps in the GMO analysis to the total variation variance components were estimated using REML (residual maximum likelihood method). From these components, relative standard deviations for repeatability and reproducibility (RSDr and RSDR) were calculated. The results showed that not only the PCR reaction but also the factors ‘DNA isolation’ and ‘PCR day’ are important factors for the total variance and should therefore be included in the in-house validation. It is proposed to use a statistical model to estimate these factors from a large dataset of initial validations so that for similar GMO methods in the future, only the PCR step needs to be validated. The resulting data are discussed in the light of agreed European criteria for qualified GMO detection methods

Added value of 18F-FDG-PET/CT and cardiac CTA in suspected transcatheter aortic valve endocarditis

Backgrounds: Transcatheter-implanted aortic valve infective endocarditis (TAVI-IE) is difficult to diagnose when relying on the Duke Criteria. Our aim was to assess the additional diagnostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission/computed tomography (PET/CT) and cardiac computed tomography angiography (CTA) in suspected TAVI-IE. Methods: A multicenter retrospective analysis was performed in all patients who underwent 18F-FDG-PET/CT and/or CTA with suspected TAVI-IE. Patients were first classified with Duke Criteria and after adding 18F-FDG-PET/CT and CTA, they were classified with European Society of Cardiology (ESC) criteria. The final diagnosis was determined by our Endocarditis Team based on ESC guideline recommendations. Results: Thirty patients with suspected TAVI-IE were included. 18F-FDG-PET/CT was performed in all patients and Cardiac CTA in 14/30. Using the Modified Duke Criteria, patients were classified as 3% rejected (1/30), 73% possible (22/30), and 23% definite (7/30) TAVI-IE. Adding 18F-FDG-PET/CT and CTA supported the reclassification of 10 of the 22 possible cases as “definite TAVI-IE” (5/22) or “rejected TAVI-IE” (5/22). This changed the final diagnosis to 20% rejected (6/30), 40% possible (12/30), and 40% definite (12/30) TAVI-IE. Conclusions: Addition of 18F-FDG-PET/CT and/or CTA changed the final diagnosis in 33% of patients and proved to be a valuable diagnostic tool in patients with suspected TAVI-IE

BMI Development of Normal Weight and Overweight Children in the PIAMA Study

Background: There is evidence that rapid weight gain during the first year of life is associated with overweight later in life. However, results from studies exploring other critical periods for the development of overweight are inconsistent. Objective: The objective was to investigate BMI development to assess at what ages essential differences between normal weight and overweight children occur, and to assess which age intervals the most strongly influence the risk of overweight at 8 years of age. Methods: Longitudinal weight and height data

Impacts of meeting minimum access on critical earth systems amidst the Great Inequality

The Sustainable Development Goals aim to improve access to resources and services, reduce environmental degradation, eradicate poverty and reduce inequality. However, the magnitude of the environmental burden that would arise from meeting the needs of the poorest is under debate—especially when compared to much larger burdens from the rich. We show that the ‘Great Acceleration’ of human impacts was characterized by a ‘Great Inequality’ in using and damaging the environment. We then operationalize ‘just access’ to minimum energy, water, food and infrastructure. We show that achieving just access in 2018, with existing inequalities, technologies and behaviours, would have produced 2–26% additional impacts on the Earth’s natural systems of climate, water, land and nutrients—thus further crossing planetary boundaries. These hypothetical impacts, caused by about a third of humanity, equalled those caused by the wealthiest 1–4%. Technological and behavioural changes thus far, while important, did not deliver just access within a stable Earth system. Achieving these goals therefore calls for a radical redistribution of resources

Prior knowledge based mining functional modules from Yeast PPI networks with gene ontology

<p>Abstract</p> <p>Background</p> <p>In the literature, there are fruitful algorithmic approaches for identification functional modules in protein-protein interactions (PPI) networks. Because of accumulation of large-scale interaction data on multiple organisms and non-recording interaction data in the existing PPI database, it is still emergent to design novel computational techniques that can be able to correctly and scalably analyze interaction data sets. Indeed there are a number of large scale biological data sets providing indirect evidence for protein-protein interaction relationships.</p> <p>Results</p> <p>The main aim of this paper is to present a prior knowledge based mining strategy to identify functional modules from PPI networks with the aid of Gene Ontology. Higher similarity value in Gene Ontology means that two gene products are more functionally related to each other, so it is better to group such gene products into one functional module. We study (i) to encode the functional pairs into the existing PPI networks; and (ii) to use these functional pairs as pairwise constraints to supervise the existing functional module identification algorithms. Topology-based modularity metric and complex annotation in MIPs will be used to evaluate the identified functional modules by these two approaches.</p> <p>Conclusions</p> <p>The experimental results on Yeast PPI networks and GO have shown that the prior knowledge based learning methods perform better than the existing algorithms.</p