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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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- Henkel, C., et al.
(författare)
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Molecular line emission in NGC 4945, imaged with ALMA
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 615
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Tidskriftsartikel (refereegranskat)abstract
- NGC 4945 is one of the nearest (D ≈ 3.8 Mpc; 1 00 ≈ 19 pc) starburst galaxies. To investigate the structure, dynamics, and composition of the dense nuclear gas of this galaxy, ALMA band 3 (λ ≈ 3−4 mm) observations were carried out with ≈2 00 resolution. Three HCN and two HC + isotopologues, CS, C 3 H 2 , SiO, HCO, and CH 3 C 2 H were measured. Spectral line imaging demonstrates the presence of a rotating nuclear disk of projected size 10 00 × 2 00 reaching out to a galactocentric radius of r ≈ 100 pc with position angle PA = 45 ◦ ± 2 ◦ , inclination i = 75 ◦ ± 2 ◦ and an unresolved bright central core of size <∼ 2 00 . The continuum source, representing mostly free-free radiation from star forming regions, is more compact than the nuclear disk by a linear factor of two but shows the same position angle and is centered 0 00 . 39 ± 0 00 . 14 northeast of the nuclear accretion disk defined by H 2 O maser emission. Near the systemic velocity but outside the nuclear disk, both HCN J = 1 → 0 and CS J = 2 → 1 delineate molecular arms of length >∼ 15 00 ( >∼ 285 pc) on opposite sides of the dynamical center. These are connected by a (deprojected) ≈ 0.6 kpc sized molecular bridge, likely a dense gaseous bar seen almost ends-on, shifting gas from the front and back side into the nuclear disk. Modeling this nuclear disk located farther inside (r <∼ 100 pc) with tilted rings provides a good fit by inferring a coplanar outflow reaching a characteristic deprojected velocity of ≈50 km s −1 . All our molecular lines, with the notable exception of CH 3 C 2 H, show significant absorption near the systemic velocity (≈571 km s −1 ), within the range ≈500-660 km s −1 . Apparently, only molecular transitions with low critical H 2 density (n crit<∼ 10 4 cm −3 ) do not show absorption. The velocity field of the nuclear disk, derived from CH 3 C 2 H, provides evidence for rigid rotation in the inner few arcseconds and a dynamical mass of M tot = (2.1 ± 0.2) × 10 8 M inside a galactocentric radius of 2 00 . 45 (≈45 pc), with a significantly flattened rotation curve farther out. Velocity integrated line intensity maps with most pronounced absorption show molecular peak positions up to ≈1 00 . 5 (≈30 pc) southwest of the continuum peak, presumably due to absorption, which appears to be most severe slightly northeast of the nuclear maser disk. A nitrogen isotope ratio of 14 N/ 15 N ≈ 200-450 is estimated. This range of values is much higher then previously reported on a tentative basis. Therefore, because 15 N is less abundant than expected, the question for strong 15 N enrichment by massive star ejecta in starbursts still remains to be settled.
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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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- Tsakonas, G, et al.
(författare)
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ALK-Brain Prognostic Index-Preliminary Study of a Prognostic Tool for Patients with ALK-Rearranged, Non-small Cell Lung Cancer and Brain Metastases
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disease-specific Graded Prognostic Assessment (DS-GPA) is the most validated prognostic tool for patients with brain metastasized lung cancer. The Lung-molGPA scoring system was recently introduced for oncogenic-driven brain metastasized lung cancer, but has not yet been validated in cohorts including only ALK-translocated tumors. Methods: We designed a retrospective cohort study consisting of 44 patients with brain metastasized ALK-positive, non-small cell lung cancer (NSCLC) who were treated between January 2009 and November 2019 at Karolinska University Hospital in Stockholm, Sweden. Information about demographics and clinicopathological parameters were collected. Predictors of overall survival (OS) were identified by Cox regression analyses. A bootstrap validation with 1000 samples was performed in order to compare the different prognostic scores. Results: The variables found to independently influence OS in the multivariate analysis, i.e., PS, sex and brain metastases at diagnosis, were used as prognostic variables in our new prognostic index (ALK-BPI). Patients were divided into two prognostic groups. The median OS was 65.7 months for the good prognostic group and 22.7 months for the poor prognostic group (p = 0.0068). In the univariate analysis of the different prognostic scores, ALK-BPI performed better than the others (HR = 3.6; 95% CI: 1.3–9.9). The mean C-statistics of the different prognostic scores were compared to each other, and no significant difference was observed. Conclusion: We propose the ALK-BPI score as a new prognostic tool that can easily be applied for ALK-positive lung cancer patients with brain metastases in daily clinical practice, as it has at least the same prognostic value as Lung-molGPA.
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| 17. |
- Alipour, F, et al.
(författare)
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Social issues and post-disaster recovery: A qualitative study in an Iranian context
- 2015
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Ingår i: INTERNATIONAL SOCIAL WORK. - : SAGE Publications. - 0020-8728 .- 1461-7234. ; 58:5, s. 689-703
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The physical impacts of a disaster are usually the most obvious impacts, and they are easily measured. However, there is not sufficient in-depth understanding of social issues arising after disasters. This qualitative study explored three main concepts regarding social issues after an earthquake in an Iranian context: social vulnerability, social uncertainty and confusion, and ignorance of local social capital. Negligence of social issues after disasters leads to delays in returning back to normal life. Policymakers are encouraged to take a comprehensive plan into account which considers these issues and facilitates the process of returning to normal life after earthquakes.
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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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| 20. |
- Blokzijl, Andries, et al.
(författare)
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Protein biomarker validation via proximity ligation assays
- 2014
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Ingår i: Biochimica et Biophysica Acta - Proteins and Proteomics. - : Elsevier BV. - 1570-9639 .- 1878-1454. ; 1844:5, s. 933-939
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Forskningsöversikt (refereegranskat)abstract
- The ability to detect minute amounts of specific proteins or protein modifications in blood as biomarkers for a plethora of human pathological conditions holds great promise for future medicine. Despite a large number of plausible candidate protein biomarkers published annually, the translation to clinical use is impeded by factors such as the required size of the initial studies, and limitations of the technologies used. The proximity ligation assay (PLA) is a versatile molecular tool that has the potential to address some obstacles, both in validation of biomarkers previously discovered using other techniques, and for future routine clinical diagnostic needs. The enhanced specificity of PIA extends the opportunities for large-scale, high-performance analyses of proteins. Besides advantages in the form of minimal sample consumption and an extended dynamic range, the PLA technique allows flexible assay reconfiguration. The technology can be adapted for detecting protein complexes, proximity between proteins in extracellular vesicles or in circulating tumor cells, and to address multiple post-translational modifications in the same protein molecule. We discuss herein requirements for biomarker validation, and how PLA may play an increasing role in this regard. We describe some recent developments of the technology, including proximity extension assays, the use of recombinant affinity reagents suitable for use in proximity assays, and the potential for single cell proteomics. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. (C) 2013 Elsevier B.V. All rights reserved.
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| 21. |
- Danad, Ibrahim, et al.
(författare)
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Carotid artery intima-media thickness, but not coronary artery calcium, predicts coronary vascular resistance in patients evaluated for coronary artery disease
- 2012
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Ingår i: European Heart Journal: Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 13:4, s. 317-323
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Tidskriftsartikel (refereegranskat)abstract
- Aims There is growing evidence that coronary artery disease (CAD) affects not only the conduit epicardial coronary arteries, but also the microvascular coronary bed. Moreover, coronary microvascular dysfunction (CMVD) often precedes the stage of clinically overt epicardial CAD. Coronary artery calcium (CAC) and carotid intima-media thickness (C-IMT) measured with computed tomography (CT) and ultrasound, respectively, are among the available techniques to non-invasively assess atherosclerotic burden. An increased CAC score and C-IMT have also been associated with CMVD. It is therefore of interest to explore and compare the potential of CAC against C-IMT to predict minimal coronary vascular resistance (CVR). Methods and results We evaluated 120 patients (mean age 56 +/- 9 years, 58 men) without a documented history of CAD in whom and results obstructive CAD was excluded. All patients underwent C-IMT measurements, CAC scoring, and vasodilator stress O-15-water positron emission tomography (PET)/CT, during which the coronary flow reserve (CFR) and minimal CVR were analysed. Minimal CVR increased significantly with increasing tertiles of C-IMT (22 +/- 6, 27 +/- 11, and 28 +/- 9 mmHg mL(-1) min(-1) g(-1), P < 0.01), whereas the CFR was comparable across all C-IMT groups (P = 0.50). Minimal CVR increased significantly with an increase in CAC score (23 +/- 9, 27 +/- 8, 32 +/- 10, and 32 +/- 7 mmHg mL(-1) min(-1) g(-1). P < 0.01), whereas the CFR did not show a significant decrease with higher CAC scores (P = 0.18). Multivariable regression analysis revealed that C-IMT (P = 0.03), but not CAC, was independently associated with minimal CVR. Conclusion C-IMT, but not CAC score, independently predicts minimal CVR in patients with multiple cardiovascular risk factors and suspected of CAD.
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| 22. |
- Doulabi, Ehsan Manouchehri, et al.
(författare)
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Surface protein profiling of prostate-derived extracellular vesicles by mass spectrometry and proximity assays
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1402-
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) are mediators of intercellular communication and a promising class of biomarkers. Surface proteins of EVs play decisive roles in establishing a connection with recipient cells, and they are putative targets for diagnostic assays. Analysis of the surface proteins can thus both illuminate the biological functions of EVs and help identify potential biomarkers. We developed a strategy combining high-resolution mass spectrometry (HRMS) and proximity ligation assays (PLA) to first identify and then validate surface proteins discovered on EVs. We applied our workflow to investigate surface proteins of small EVs found in seminal fluid (SF-sEV). We identified 1,014 surface proteins and verified the presence of a subset of these on the surface of SF-sEVs. Our work demonstrates a general strategy for deep analysis of EVs’ surface proteins across patients and pathological conditions, proceeding from unbiased screening by HRMS to ultra-sensitive targeted analyses via PLA.
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| 23. |
- Gu, Gucci Jijuan, et al.
(författare)
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Elevated Serum GAD65 and GAD65-GADA Immune Complexes in Stiff Person Syndrome.
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Glutamic acid decarboxylase 65 (GAD65) and autoantibodies specific for GAD65 (GADA) are associated with autoimmune diseases including Stiff Person Syndrome (SPS) and Type 1 diabetes (T1D). GADA is recognized as a biomarker of value for clinical diagnosis and prognostication in these diseases. Nonetheless, it remains medically interesting to develop sensitive and specific assays to detect GAD65 preceding GADA emergence, and to monitor GADA-GAD65 immune complexes in blood samples. In the present study, we developed a highly sensitive proximity ligation assay to measure serum GAD65. This novel assay allowed detection of as little as 0.65 pg/ml GAD65. We were also able to detect immune complexes involving GAD65 and GADA. Both free GAD65 and GAD65-GADA levels were significantly higher in serum samples from SPS patients compared to healthy controls. The proximity ligation assays applied for detection of GAD65 and its immune complexes may thus enable improved diagnosis and better understanding of SPS.
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| 25. |
- Hassan, Amin S, et al.
(författare)
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A Stronger Innate Immune Response During Hyperacute HIV-1 Infection is associated with ACUTE retroviral syndrome
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 73:5, s. 832-841
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute retroviral syndrome (ARS) is associated with HIV-1 subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS.METHODS: Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive from Kenya, Rwanda, Uganda, Zambia and Sweden were analysed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on eleven symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS.RESULTS: Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (n=36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% CI: 1.7-28.8], p=0.003). IP-10 was fourteen-fold higher during hAHI, elevated in seven of the eleven symptoms, and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4-96.6) and specificity of 100.0% (95% CI: 90.3-100.0).CONCLUSIONS: A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity.
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