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- Pantazis, N, et al.
(författare)
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Determining the likely place of HIV acquisition for migrants in Europe combining subject-specific information and biomarkers data
- 2019
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 28:7, s. 1979-1997
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Tidskriftsartikel (refereegranskat)abstract
- In most HIV-positive individuals, infection time is only known to lie between the time an individual started being at risk for HIV and diagnosis time. However, a more accurate estimate of infection time is very important in certain cases. For example, one of the objectives of the Advancing Migrant Access to Health Services in Europe (aMASE) study was to determine if HIV-positive migrants, diagnosed in Europe, were infected pre- or post-migration. We propose a method to derive subject-specific estimates of unknown infection times using information from HIV biomarkers’ measurements, demographic, clinical, and behavioral data. We assume that CD4 cell count (CD4) and HIV-RNA viral load trends after HIV infection follow a bivariate linear mixed model. Using post-diagnosis CD4 and viral load measurements and applying the Bayes’ rule, we derived the posterior distribution of the HIV infection time, whereas the prior distribution was informed by AIDS status at diagnosis and behavioral data. Parameters of the CD4–viral load and time-to-AIDS models were estimated using data from a large study of individuals with known HIV infection times (CASCADE). Simulations showed substantial predictive ability (e.g. 84% of the infections were correctly classified as pre- or post-migration). Application to the aMASE study ( n = 2009) showed that 47% of African migrants and 67% to 72% of migrants from other regions were most likely infected post-migration. Applying a Bayesian method based on bivariate modeling of CD4 and viral load, and subject-specific information, we found that the majority of HIV-positive migrants in aMASE were most likely infected after their migration to Europe.
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- Andreeva, M. A., et al.
(författare)
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Nuclear resonant reflectivity with standing waves for the investigation of a thin 57Fe layer buried inside a superconducting Si/[Mo/Si]45/57Fe/Nb multilayer
- 2008
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Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier BV. - 0168-583X .- 1872-9584. ; 266:1, s. 187-196
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Tidskriftsartikel (refereegranskat)abstract
- A special multilayer sample Si/[Mo/Si]45/57Fe/Nb has been prepared for the depth selective investigations of the hyperfine fields in thin iron layer at low temperatures above and below the superconducting transition in the top Nb layer (Tc 8 K) by means of the nuclear resonant reflectivity with standing waves. The periodic multilayer [Mo/Si]45 below the iron layer in our sample was used as “a standing wave generator”. A weak magnetic hyperfine splitting in the 57Fe layer was detected just at low temperature. A slight variation of the nuclear resonant reflectivity time spectra measured above and below Tc was observed. At first it was supposed that this change of the spectrum shape is caused by the spatial modulation of ferromagnetic domains in the 57Fe layer caused by a proximity effect. A closer analysis, however, reveals that the spectrum variations are due to just the changes of the relative weights of the magnetic and paramagnetic phases in 57Fe layer.
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- Kuchenbaecker, K, et al.
(författare)
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The transferability of lipid loci across African, Asian and European cohorts
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4330-
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Tidskriftsartikel (refereegranskat)abstract
- Most genome-wide association studies are based on samples of European descent. We assess whether the genetic determinants of blood lipids, a major cardiovascular risk factor, are shared across populations. Genetic correlations for lipids between European-ancestry and Asian cohorts are not significantly different from 1. A genetic risk score based on LDL-cholesterol-associated loci has consistent effects on serum levels in samples from the UK, Uganda and Greece (r = 0.23–0.28, p < 1.9 × 10−14). Overall, there is evidence of reproducibility for ~75% of the major lipid loci from European discovery studies, except triglyceride loci in the Ugandan samples (10% of loci). Individual transferable loci are identified using trans-ethnic colocalization. Ten of fourteen loci not transferable to the Ugandan population have pleiotropic associations with BMI in Europeans; none of the transferable loci do. The non-transferable loci might affect lipids by modifying food intake in environments rich in certain nutrients, which suggests a potential role for gene-environment interactions.
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- Kamali-Moghaddam, Masood, et al.
(författare)
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Sensitive detection of A beta protofibrils by proximity ligation : relevance for Alzheimer's disease
- 2010
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Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 11, s. 124-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Protein aggregation plays important roles in several neurodegenerative disorders. For instance, insoluble aggregates of phosphorylated tau and of A beta peptides are cornerstones in the pathology of Alzheimer's disease. Soluble protein aggregates are therefore potential diagnostic and prognostic biomarkers for their cognate disorders. Detection of the aggregated species requires sensitive tools that efficiently discriminate them from monomers of the same proteins. Here we have established a proximity ligation assay (PLA) for specific and sensitive detection of A beta protofibrils via simultaneous recognition of three identical determinants present in the aggregates. PLA is a versatile technology in which the requirement for multiple target recognitions is combined with the ability to translate signals from detected target molecules to amplifiable DNA strands, providing very high specificity and sensitivity. Results: For specific detection of A beta protofibrils we have used a monoclonal antibody, mAb158, selective for A beta protofibrils in a modified PLA, where the same monoclonal antibody was used for the three classes of affinity reagents required in the assay. These reagents were used for detection of soluble Ab aggregates in solid- phase reactions, allowing detection of just 0.1 pg/ml A beta protofibrils, and with a dynamic range greater than six orders of magnitude. Compared to a sandwich ELISA setup of the same antibody the PLA increases the sensitivity of the Ab protofibril detection by up to 25- fold. The assay was used to measure soluble Ab aggregates in brain homogenates from mice transgenic for a human allele predisposing to A beta aggregation. Conclusions: The proximity ligation assay is a versatile analytical technology for proteins, which can provide highly sensitive and specific detection of A beta aggregates - and by implication other protein aggregates of relevance in Alzheimer's disease and other neurodegenerative disorders.
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- Tavakol, M, et al.
(författare)
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Diagnostic Approach to the Patients with Suspected Primary Immunodeficiency
- 2020
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Ingår i: Endocrine, metabolic & immune disorders drug targets. - : Bentham Science Publishers Ltd.. - 2212-3873 .- 1871-5303. ; 20:2, s. 157-171
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Tidskriftsartikel (refereegranskat)abstract
- Primary immunodeficiency diseases (PIDs) are a group of more than 350 disorders affecting distinct components of the innate and adaptive immune systems. In this review, the classic and advanced stepwise approach towards the diagnosis of PIDs are simplified and explained in detail.Results:Susceptibility to recurrent infections is the main hallmark of almost all PIDs. However, noninfectious complications attributable to immune dysregulation presenting with lymphoproliferative and/or autoimmune disorders are not uncommon. Moreover, PIDs could be associated with misleading presentations including allergic manifestations, enteropathies, and malignancies.Conclusion:Timely diagnosis is the most essential element in improving outcome and reducing the morbidity and mortality in PIDs. This wouldn’t be possible unless the physicians keep the diagnosis of PID in mind and be sufficiently aware of the approach to these patients.
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