| 1521. |
- Brum, Wagner S., et al.
(författare)
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A blood-based biomarker workflow for optimal tau-PET referral in memory clinic settings
- 2024
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Ingår i: Nature Communications. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Blood-based biomarkers for screening may guide tau positrion emissition tomography (PET) scan referrals to optimize prognostic evaluation in Alzheimer’s disease. Plasma Aβ42/Aβ40, pTau181, pTau217, pTau231, NfL, and GFAP were measured along with tau-PET in memory clinic patients with subjective cognitive decline, mild cognitive impairment or dementia, in the Swedish BioFINDER-2 study (n = 548) and in the TRIAD study (n = 179). For each plasma biomarker, cutoffs were determined for 90%, 95%, or 97.5% sensitivity to detect tau-PET-positivity. We calculated the percentage of patients below the cutoffs (who would not undergo tau-PET; “saved scans”) and the tau-PET-positivity rate among participants above the cutoffs (who would undergo tau-PET; “positive predictive value”). Generally, plasma pTau217 performed best. At the 95% sensitivity cutoff in both cohorts, pTau217 resulted in avoiding nearly half tau-PET scans, with a tau-PET-positivity rate among those who would be referred for a scan around 70%. And although tau-PET was strongly associated with subsequent cognitive decline, in BioFINDER-2 it predicted cognitive decline only among individuals above the referral cutoff on plasma pTau217, supporting that this workflow could reduce prognostically uninformative tau-PET scans. In conclusion, plasma pTau217 may guide selection of patients for tau-PET, when accurate prognostic information is of clinical value.
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| 1522. |
- Brum, Wagner S., et al.
(författare)
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A three-range approach enhances the prognostic utility of CSF biomarkers in Alzheimer's disease.
- 2022
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Ingår i: Alzheimer's & dementia (New York, N. Y.). - : Wiley. - 2352-8737. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease consensus recommends biomarker dichotomization, a practice with well-described clinical strengths and methodological limitations. Although neuroimaging studies have explored alternative biomarker interpretation strategies, a formally defined three-range approach and its prognostic impact remains under-explored for cerebrospinal fluid (CSF) biomarkers .With two-graph receiver-operating characteristics based on different reference schemes, we derived three-range cut-points for CSF Elecsys biomarkers. According to baseline CSF status, we assessed the prognostic utility of this in predicting risk of clinical progression and longitudinal trajectories of cognitive decline and amyloid-beta (Aβ) positron emission tomography (PET) accumulation in non-demented individuals (Alzheimer's Disease Neuroimaging Initiative [ADNI]; n = 1246). In all analyses, we compared herein-derived three-range CSF cut-points to previously described binary ones.In our main longitudinal analyses, we highlight CSF p-tau181/Aβ1-42 three-range cut-points derived based on the cognitively normal Aβ-PET negative versus dementia Aβ-PET positive reference scheme for best depicting a prognostically relevant biomarker abnormality range. Longitudinally, our approach revealed a divergent intermediate cognitive trajectory undetected by dichotomization and a clearly abnormal group at higher risk for cognitive decline, with power analyses suggesting the latter group as potential trial enrichment candidates. Furthermore, we demonstrate that individuals with intermediate-range CSF status have similar rates of Aβ deposition to those in the clearly abnormal group.The proposed approach can refine clinico-biological prognostic assessment and potentially enhance trial recruitment, as it captures faster biomarker-related cognitive decline in comparison to binary cut-points. Although this approach has implications for trial recruitment and observational studies, further discussion is needed regarding clinical practice applications.
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| 1523. |
- Brum, Wagner S., et al.
(författare)
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Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals
- 2024
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Ingår i: Alzheimer's and Dementia. - 1552-5260 .- 1552-5279. ; 20:2, s. 1284-1297
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data. METHODS: We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p-tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CVI) and between-subject (CVG) BV, analytical variation, and reference change values (RCV). RESULTS: Biomarkers presented considerable variability in CVI and CVG. Aβ42/Aβ40 had the lowest CVI (≈ 3%) and p-tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase). DISCUSSION: BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between-subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result.
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| 1524. |
- Büntgen, Ulf, et al.
(författare)
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Cooling and societal change during the Late Antique Little Ice Age from 536 to around 660 AD
- 2016
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Ingår i: Nature Geoscience. - 1752-0894 .- 1752-0908. ; 9:3, s. 231-236
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Tidskriftsartikel (refereegranskat)abstract
- Climatic changes during the first half of the Common Era have been suggested to play a role in societal reorganizations in Europe and Asia. In particular, the sixth century coincides with rising and falling civilizations, pandemics, human migration and political turmoil. Our understanding of the magnitude and spatial extent as well as the possible causes and concurrences of climate change during this period is, however, still limited. Here we use tree-ring chronologies from the Russian Altai and European Alps to reconstruct summer temperatures over the past two millennia. We find an unprecedented, long-lasting and spatially synchronized cooling following a cluster of large volcanic eruptions in 536, 540 and 547 AD, which was probably sustained by ocean and sea-ice feedbacks, as well as a solar minimum. We thus identify the interval from 536 to about 660 AD as the Late Antique Little Ice Age. Spanning most of the Northern Hemisphere, we suggest that this cold phase be considered as an additional environmental factor contributing to the establishment of the Justinian plague, transformation of the eastern Roman Empire and collapse of the Sasanian Empire, movements out of the Asian steppe and Arabian Peninsula, spread of Slavic-speaking peoples and political upheavals in China.
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| 1525. |
- Büntgen, Ulf, et al.
(författare)
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Reply to 'Limited Late Antique cooling'
- 2017
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 10:4, s. 243-243
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 1526. |
- Carlander, C., et al.
(författare)
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HPV Types in Cervical Precancer by HIV Status and Birth Region: A Population-Based Register Study
- 2020
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1055-9965. ; 29:12, s. 2662-2668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data are lacking regarding which human papillomavirus (HPV) types cause high-grade cervical neoplasia (CIN2+) in people with HIV in Europe. We assessed which HPV types are associated with CIN2+ in women living in Sweden by HIV status. Methods: The Swedish National HIV Registry, the Swedish Population Registry, and the Swedish National Cervical Screening Registry were linked. CIN2+ tissue blocks of 130 women living with HIV (WLWH) and 234 HIV-negative women, matched for country of birth (1:2), were retrieved from bio-banks and HPV genotyped. Adjusted ORs (adjOR), stratified by country of birth, were calculated using conditional logistic regression. Matching was broken for cross-group comparisons. Results: WLWH with CIN2 were less likely to have HPV16 [14% vs. 40%; adjOR 0.1; 95% confidence interval (CI), 0.04-0.56] than HIV-negative women, but among women with CIN3, there was no difference in HPV16 prevalence by HIV status (adjOR 0.9; 95% CI, 0.51-1.70). WLWH were six times more likely to have HPV35 in CIN3 than HIV-negative women (adjOR 6.2; 95% CI, 1.3-30.4). WLWH from sub-Saharan Africa (SSA) had less 9-valent vaccine types, compared with both HIV-negative women born in Sweden (adjOR 0.1; 95% CI, 0.02-0.44) and WLWH born in Sweden (adjOR 0.1; 95% CI, 0.01-0.73), mostly because of decreased HPV16 and increased HPV35. Conclusions: WLWH from SSA were less likely to be covered by the 9-valent vaccine, mostly due to less HPV16 and more HPV35. Impact: This could have implications for HPV vaccines, currently not including HPV35, and for HPV-screening algorithms in women with origin from SSA.
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| 1527. |
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| 1528. |
- Cerruti, M., et al.
(författare)
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Target of Opportunity Observations of Blazars with HESS
- 2017
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Ingår i: HIGH ENERGY GAMMA-RAY ASTRONOMY. - : American Institute of Physics (AIP). - 9780735414563
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Konferensbidrag (refereegranskat)abstract
- The very high energy (VHE, E > 100 GeV) sky is dominated by blazars, radio-loud active galactic nuclei whose relativistic jet is closely aligned with the line of sight. Blazars are characterized by rapid variability at all wavelengths and thus an important part of the H.E.S.S. blazar program is devoted to target of opportunity (ToO) observations. H.E.S.S. triggers blazar ToOs on the basis of publicly available blazar observations at longer wavelengths (optical, X-rays, and gamma-rays), from private optical observations with the ATOM telescope, and from private communications by gamma-ray partners in the context of MoUs. In 2015, about 70 hours of H.E.S.S. data were taken in the form of blazar ToOs, which represents 15% of all extragalactic observations. In this contribution, we present the H.E.S.S. blazar ToO status, and we focus on two major results from the 2015 season: the detection of VHE emission from 3C 279 during the June 2015 flare, and the discovery of PKS 0736+017 as a new VHE quasar.
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| 1529. |
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| 1530. |
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