629 research outputs found

    POLARIS: polygenic LD-adjusted risk score approach for set-based analysis of GWAS data

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    Polygenic risk scores (PRSs) are a method to summarise the additive trait variance captured by a set of SNPs, and can increase the power of set-based analyses by leveraging public GWAS datasets. PRS aims to assess the genetic liability to some phenotype on the basis of polygenic risk for the same or di�erent phenotype estimated from independent data. We propose the application of PRSs as a set-based method with an additional component of adjustment for linkage disequilibrium (LD), with potential extension of the PRS approach to analyse biologically meaningful SNP sets. We call this method POLARIS: POlygenic Ld-Adjusted RIsk Score. POLARIS identi�es the LD-structure of SNPs using spectral decomposition of the SNP correlation matrix and replaces the individuals' SNP allele counts with LD-adjusted dosages. Using a raw genotype dataset together with SNP e�ect sizes from a second independent dataset, POLARIS can be used for set-based analysis. MAGMA is an alternative set-based approach employing principal component analysis to account for LD between markers in a raw genotype dataset. We used simulations, both with simple constructed and real LD-structure, to compare the power of these methods. POLARIS shows more power than MAGMA applied to the raw genotype dataset only, but less or comparable power to combined analysis of both datasets. POLARIS has the advantages that it produces a risk score per person per set using all available SNPs, and aims to increase power by leveraging the e�ect sizes from the discovery set in a self-contained test of association in the test dataset

    IgG antibody production and persistence to 6 months following SARS-CoV-2 vaccination: a Northern Ireland observational study

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    BACKGROUND: This study evaluates spike protein IgG antibody response following Oxford-AstraZeneca COVID-19 vaccination using the AbC-19™ lateral flow device. METHODS: Plasma samples were collected from n=111 individuals from Northern Ireland. The majority were >50 years old and/or clinically vulnerable. Samples were taken at five timepoints from pre-vaccination until 6-months post-first dose. RESULTS: 20.3% of participants had detectable IgG responses pre-vaccination, indicating prior COVID-19. Antibodies were detected in 86.9% of participants three weeks after the first vaccine dose, falling to 74.7% immediately prior to the second dose, and rising to 99% three weeks post-second vaccine. At 6-months post-first dose, this decreased to 90.5%. At all timepoints, previously infected participants had significantly higher antibody levels than those not previously infected. CONCLUSION: This study demonstrates that strong anti-spike protein antibody responses are evoked in almost all individuals that receive two doses of Oxford-AstraZeneca vaccine, and largely persist beyond six months after first vaccination

    User experience analysis of AbC-19 Rapid Test via lateral flow immunoassays for self-administrated SARS-CoV-2 antibody testing

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    Abstract Lateral flow immunoassays are low cost, rapid and highly efficacious point-of-care devices, which have been used for SARS-CoV-2 antibody testing by professionals. However, there is a lack of understanding about how self-administered tests are used by the general public for mass testing in different environmental settings. The purpose of this study was to assess the user experience (UX) (including usability) of a self-testing kit to identify COVID-19 antibodies used by a representative sample of the public in their cars, which included 1544 participants in Northern Ireland. The results based on 5-point Likert ratings from a post-test questionnaire achieved an average UX score of 96.03% [95% confidence interval (CI) 95.05–97.01%], suggesting a good degree of user experience. The results of the Wilcoxon rank sum tests suggest that UX scores were independent of the user’s age and education level although the confidence in this conclusion could be strengthened by including more participants aged younger than 18 and those with only primary or secondary education. The agreement between the test result as interpreted by the participant and the researcher was 95.85% [95% CI 94.85–96.85%], Kappa score 0.75 [95% CI 0.69–0.81] (indicating substantial agreement). Text analysis via the latent Dirichlet allocation model for the free text responses in the survey suggest that the user experience could be improved for blood-sample collection, by modifying the method of sample transfer to the test device and giving clearer instructions on how to interpret the test results. The overall findings provide an insight into the opportunities for improving the design of SARS-CoV-2 antibody testing kits to be used by the general public and therefore inform protocols for future user experience studies of point-of-care tests

    Impulsivity is Associated with Increased Metabolism in the Fronto-Insular Network in Parkinson’s Disease

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    Front. Behav. Neurosci. 9:317. doi: 10.3389/fnbeh.2015.00317 Various neuroimaging studies demonstrated that the fronto-insular network is implicated in impulsive behavior. We compared glucose metabolism (as a proxy measure of neural activity) among 24 patients with Parkinson’s disease (PD) who presented with low or high levels of impulsivity based on the Barratt Impulsiveness Scale 11 (BIS) scores. Subjects underwent 18-fluorodeoxyglucose positron emission tomography (FDG-PET) and the voxel-wise group difference of FDG-metabolism was analyzed in Statistical Parametric Mapping (SPM8). Subsequently, we performed a partial correlation analysis between the FDG-metabolism and BIS scores, controlling for covariates (i.e., age, sex, severity of disease and levodopa equivalent daily doses). Voxel-wise group comparison revealed higher FDG-metabolism in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and right insula in patients with higher impulsivity scores. Moreover, there was a positive correlation between the FDG-metabolism and BIS scores. Our findings provide evidence that high impulsivity is associated with increased FDG-metabolis

    Early pre-radiographic structural pathology precedes the onset of accelerated knee osteoarthritis.

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    BACKGROUND: Accelerated knee osteoarthritis (AKOA) is characterized by more pain, impaired physical function, and greater likelihood to receive a joint replacement compared to individuals who develop the typical gradual onset of disease. Prognostic tools are needed to determine which structural pathologies precede the development of AKOA compared to individuals without AKOA. Therefore, the purpose of this manuscript was to determine which pre-radiographic structural features precede the development of AKOA. METHODS: The sample comprised participants in the Osteoarthritis Initiative (OAI) who had at least one radiographically normal knee at baseline (Kellgren-Lawrence [KL] grade  3) and No AKOA. The index visit was the study visit when participants met criteria for AKOA or a matched timepoint for those who did not develop AKOA. Magnetic resonance (MR) images were assessed for 12 structural features at the OAI baseline, and 1 and 2 years prior to the index visit. Separate logistic regression models (i.e. OAI baseline, 1 and 2 years prior) were used to determine which pre-radiographic structural features were more likely to antedate the development of AKOA compared to individuals not developing AKOA. RESULTS: At the OAI baseline visit, degenerative cruciate ligaments (Odds Ratio [OR] = 2.2, 95% Confidence Interval [CI] = 1.3,3.5), infrapatellar fat pad signal intensity alteration (OR = 2.0, 95%CI = 1.2,3.2), medial/lateral meniscal pathology (OR = 2.1/2.4, 95%CI = 1.3,3.4/1.5,3.8), and greater quantitative knee effusion-synovitis (OR = 2.2, 95%CI = 1.4,3.4) were more likely to antedate the development of AKOA when compared to those that did not develop AKOA. These results were similar at one and two years prior to disease onset. Additionally, medial meniscus extrusion at one year prior to disease onset (OR = 3.5, 95%CI = 2.1,6.0) increased the likelihood of developing AKOA. CONCLUSIONS: Early ligamentous degeneration, effusion/synovitis, and meniscal pathology precede the onset of AKOA and may be prognostic biomarkers
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