| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Muscarella, Robert, et al.
(författare)
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The global abundance of tree palms
- 2020
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 29:9, s. 1495-1514
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Tidskriftsartikel (refereegranskat)abstract
- AimPalms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change.LocationTropical and subtropical moist forests.Time periodCurrent.Major taxa studiedPalms (Arecaceae).MethodsWe assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure.ResultsOn average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work.ConclusionsTree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests.
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| 4. |
- Hoshino, Ayuko, et al.
(författare)
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Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers
- 2020
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 182:4, s. 1044-
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Tidskriftsartikel (refereegranskat)abstract
- There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n =151) and plasma-derived (n =120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
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| 5. |
- Needham, E. J., et al.
(författare)
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Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:11, s. 4097-4107
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible. Needham et al. reveal elevations in blood biomarkers of brain injury in patients hospitalised with COVID-19. The changes, which were severity-dependent, were associated with dysregulated immune responses including increases in pro-inflammatory cytokines and autoantibodies. Ongoing active brain injury could still be seen months after infection.
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| 6. |
- Abazajian, Kevork, et al.
(författare)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
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Tidskriftsartikel (refereegranskat)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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| 7. |
- Cooper, Declan L.M., et al.
(författare)
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Consistent patterns of common species across tropical tree communities
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 728-734
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Tidskriftsartikel (refereegranskat)abstract
- Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations 1–6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories 7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.
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| 8. |
- Frank, Brandon, et al.
(författare)
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Plasma p-tau181 shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau.
- 2022
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 18:8, s. 1523-1536
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Tidskriftsartikel (refereegranskat)abstract
- We examined the ability of plasma hyperphosphorylated tau (p-tau)181 to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL).Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables.Plasma p-tau181 discriminated AD dementia from NC, but not MCI, and correlated with dementia severity and worse neuropsychological test performance. Plasma NfL similarly discriminated diagnostic groups. Unlike plasma NfL or t-tau, p-tau181 had a direct association with cognitive diagnosis in a bootstrapped GGM.These results support plasma p-tau181 for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection.
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| 9. |
- Montoliu-Gaya, Laia, et al.
(författare)
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Optimal blood tau species for the detection of Alzheimer's disease neuropathology: an immunoprecipitation mass spectrometry and autopsy study.
- 2024
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Ingår i: Acta neuropathologica. - 1432-0533. ; 147:1
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Tidskriftsartikel (refereegranskat)abstract
- Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer's disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD. The sample included 123 participants (AD=69, non-AD=54) from the Boston University Alzheimer's disease Research Center who had an available ante-mortem plasma sample and donated their brain. Plasma samples proximate to death were analyzed by targeted IP-MS for six different tryptic phosphorylated (p-tau-181, 199, 202, 205, 217, 231), and two non-phosphorylated tau (195-205, 212-221) peptides. NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma peptide and autopsy-confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications. All tau species were increased in AD compared to non-AD, but p-tau217, p-tau205 and p-tau231 showed the highest fold-changes. Plasma p-tau217 (AUC=89.8), p-tau231 (AUC=83.4), and p-tau205 (AUC=81.3) all had excellent accuracy in discriminating AD from non-AD brain donors, even among those with CDR<1). Furthermore, p-tau217, p-tau205 and p-tau231 showed the highest ORs with both CERAD (ORp-tau217=15.29, ORp-tau205=5.05 and ORp-tau231=3.86) and Braak staging (ORp-tau217=14.29, ORp-tau205=5.27 and ORp-tau231=4.02) but presented increased levels at different amyloid and tau stages determined by neuropathological examination. Our findings support plasma p-tau217 as the most promising p-tau species for detecting AD brain pathology. Plasma p-tau231 and p-tau205 may additionally function as markers for different stages of the disease.
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| 10. |
- Potapov, Anton M., et al.
(författare)
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Global fine-resolution data on springtail abundance and community structure
- 2024
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Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.
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| 11. |
- Srikrishna, Meera, et al.
(författare)
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CT-based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration
- 2024
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 20:1, s. 629-640
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONCranial computed tomography (CT) is an affordable and widely available imaging modality that is used to assess structural abnormalities, but not to quantify neurodegeneration. Previously we developed a deep-learning-based model that produced accurate and robust cranial CT tissue classification.MATERIALS AND METHODSWe analyzed 917 CT and 744 magnetic resonance (MR) scans from the Gothenburg H70 Birth Cohort, and 204 CT and 241 MR scans from participants of the Memory Clinic Cohort, Singapore. We tested associations between six CT-based volumetric measures (CTVMs) and existing clinical diagnoses, fluid and imaging biomarkers, and measures of cognition.RESULTSCTVMs differentiated cognitively healthy individuals from dementia and prodromal dementia patients with high accuracy levels comparable to MR-based measures. CTVMs were significantly associated with measures of cognition and biochemical markers of neurodegeneration.DISCUSSIONThese findings suggest the potential future use of CT-based volumetric measures as an informative first-line examination tool for neurodegenerative disease diagnostics after further validation.HIGHLIGHTSComputed tomography (CT)-based volumetric measures can distinguish between patients with neurodegenerative disease and healthy controls, as well as between patients with prodromal dementia and controls.CT-based volumetric measures associate well with relevant cognitive, biochemical, and neuroimaging markers of neurodegenerative diseases.Model performance, in terms of brain tissue classification, was consistent across two cohorts of diverse nature.Intermodality agreement between our automated CT-based and established magnetic resonance (MR)-based image segmentations was stronger than the agreement between visual CT and MR imaging assessment.
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| 12. |
- Yakoub, Y., et al.
(författare)
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Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease
- 2023
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 19:12, s. 5620-5631
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset. Methods: We measured longitudinal changes in plasma amyloid-beta (A beta)(42/40) ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with A beta and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers' progression. Results: A beta(42/40) ratio concentrations decreased, while NfL and GFAP values increased over the 4-year follow-up. Apolipoprotein E (APOE) epsilon 4 carriers showed faster increase in plasma pTau181 than non-carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both A beta-PET and tau-PET positive showed faster plasma pTau181 and GFAP increase compared to PET-negative individuals. Discussion: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD.
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| 13. |
- Adie, Bailey Ashton, et al.
(författare)
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Careers, citations, bibliometrics, and impact : perspectives of new and emerging researchers
- 2024
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Ingår i: How to get published in the best tourism journals. - Cheltenham : Edward Elgar Publishing. - 9781035300600 - 9781035300594 ; , s. 211-238
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Bokkapitel (refereegranskat)abstract
- This chapter brings together invited contributions from new and emerging academics with respect to their experiences and how publishing demands affect their careers and life, and vice versa. The provision of such experiences is important as it conveys the reality of publishing from a real-world context with respect to the pressures we face, especially when starting on the academic ladder. Authors were given a broad scope with respect to their contributions and the results are provided with only very minor editing. They have also been presented anonymously, or rather collectively, because although there are clearly different perspectives, emphasises, and interpretations, there are also commonalities in the contributors’ experiences. Nevertheless, as the reader will see, there are a number of common themes that emerge. Following the perspectives of the different contributions the chapter will discuss some of the main issues that emerge and their implications, including some of the darker aspects of the pressures of publishing.
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| 14. |
- Adie, Bailey Ashton, et al.
(författare)
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Conclusions and future directions
- 2023
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Ingår i: Second Homes and Climate Change. - : Routledge. - 9781003091295 - 9780367549466 - 9781000905533 ; , s. 157-165
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Bokkapitel (refereegranskat)abstract
- This chapter presents a synthesis of the entire edited collection. In doing so, three key themes are developed which emerged from the chapter contributions. These themes are as follows: planning for climate change, second home community responses to climate change, and second home impacts on climate change. These themes are elaborated in the context of the relevant supporting chapters before the argument shifts into a discussion of future directions for second home and climate change research. In particular, the need for more research in the areas of planning and policy, psychological responses of second home owners, and overall resilience is stressed.
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| 15. |
- Adie, Bailey Ashton, et al.
(författare)
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Just Because It Seems Impossible, Doesn't Mean We Shouldn't At Least Try : The Need for Longitudinal Perspectives on Tourism Partnerships and the SDGs
- 2022
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Ingår i: Journal of Sustainable Tourism. - : Taylor & Francis Group. - 0966-9582 .- 1747-7646. ; 30:10, s. 2282-2297
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Tidskriftsartikel (refereegranskat)abstract
- Sustainable Development Goal (SDG) 17 highlights the importance that the partnership narrative plays in the implementation of SDGs. However, given the brevity of many development projects, these partnerships are often developed and concluded rapidly, with little attention given to longer-term implications or success. This paper argues that in order to create and develop partnerships that properly address the SDGs, it is imperative that a process perspective is developed that takes into account the range of stakeholders and interests, values, and the power relations between actors prior to and during the project together with a comprehensive understanding of what is success. This requires a full awareness of the project's context and previous interventions, activities, and policies. In order to illustrate the necessity of longitudinal partnerships and perspectives, a case study, a community-based development project in New Delhi, India, is used. The goal of the project has been to ensure that the community is actively involved in the entire process, eventually becoming owners of the interventions so that, when the project and partnership eventually ends, the community continues to benefit. Examples from the project are used to emphasize the importance of long-term planning and partnership driven by context-specificity, implementation processes and policy-awareness.
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| 16. |
- Ashton, Nicholas J., et al.
(författare)
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A multicentre validation study of the diagnostic value of plasma neurofilament light
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
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| 17. |
- Boberg, Mikael, et al.
(författare)
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Chiral Chromatographic Isolation on Milligram Scale of the Human African Trypanosomiasis Treatment D- and L-Eflornithine.
- 2020
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Ingår i: ACS omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:37, s. 23885-23891
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Tidskriftsartikel (refereegranskat)abstract
- Eflornithine is a recommended treatment against the otherwise fatal parasitic disease late stage human African trypanosomiasis (HAT), also known as Gambian sleeping sickness. It is administered repeatedly as a racemic mixture intravenously (IV) together with oral nifurtimox. Racemic eflornithine has been investigated in clinical trials for oral dosing. However, due to low systemic exposures at a maximum tolerated oral dose, the drug is continued to be administered IV. The eflornithine enantiomers, D- and L-eflornithine, have different affinities to the target enzyme ornithine decarboxylase, suggesting that the pharmacodynamics of the enantiomers may differ. The aim of this study was to develop a method for isolation of d- and l-eflornithine from a racemic mixture. Several chiral stationary phases (CSPs) were evaluated for enantioselectivity using supercritical fluid chromatography (SFC) or high-performance liquid chromatography (HPLC). None of the tested CSPs rendered separation of the enantiomers in SFC mode. Separation of the enantiomers with SFC on the CSP Chiralpak IG was only achieved on an analytical scale after derivatization with ortho-phthalaldehyde (OPA). This was the first reported enantioselective SFC method for an eflornithine derivate. However, due to poor stability, the eflornithine-OPA derivates degraded and no chemically pure enantiomers were obtained. The CSP that showed enantioselectivity in HPLC mode was Chirobiotic R, which resulted in a successful isolation on a semipreparative milligram scale. The isolated eflornithine enantiomers will be tested in nonclinical in vitro and in vivo studies to support and assess the feasibility of a future clinical program with an oral HAT treatment.
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| 18. |
- Bott, Lukas Thomas, et al.
(författare)
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Coulomb dissociation of O-16 into He-4 and C-12
- 2023
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Ingår i: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
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Konferensbidrag (refereegranskat)abstract
- We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
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| 19. |
- Chong, J. R., et al.
(författare)
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Blood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer's disease: a focused review on recent advances
- 2021
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 92:11, s. 1231-1241
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Forskningsöversikt (refereegranskat)abstract
- Discovery and development of clinically useful biomarkers for Alzheimer's disease (AD) and related dementias have been the focus of recent research efforts. While cerebrospinal fluid and positron emission tomography or MRI-based neuroimaging markers have made the in vivo detection of AD pathology and its consequences possible, the high cost and invasiveness have limited their widespread use in the clinical setting. On the other hand, advances in potentially more accessible blood-based biomarkers had been impeded by lack of sensitivity in detecting changes in markers of the hallmarks of AD, including amyloid-beta (A beta) peptides and phosphorylated tau (P-tau). More recently, however, emerging technologies with superior sensitivity and specificity for measuring A beta and P-tau have reported high concordances with AD severity. In this focused review, we describe several emerging technologies, including immunoprecipitation-mass spectrometry (IP-MS), single molecule array and Meso Scale Discovery immunoassay platforms, and appraise the current literature arising from their use to identify plaques, tangles and other AD-associated pathology. While there is potential clinical utility in adopting these technologies, we also highlight the further studies needed to establish A beta and P-tau as blood-based biomarkers for AD, including validation with existing large sample sets, new independent cohorts from diverse backgrounds as well as population-based longitudinal studies. In conclusion, the availability of sensitive and reliable measurements of A beta peptides and P-tau species in blood holds promise for the diagnosis, prognosis and outcome assessments in clinical trials for AD.
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| 20. |
- Chong, J. R., et al.
(författare)
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Brain atrophy and white matter hyperintensities are independently associated with plasma neurofilament light chain in an Asian cohort of cognitively impaired patients with concomitant cerebral small vessel disease
- 2023
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Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionPlasma neurofilament light chain (NfL) is a potential biomarker for neurodegeneration in Alzheimer's disease (AD), ischemic stroke, and non-dementia cohorts with cerebral small vessel disease (CSVD). However, studies of AD in populations with high prevalence of concomitant CSVD to evaluate associations of brain atrophy, CSVD, and amyloid beta (A beta) burden on plasma NfL are lacking. MethodsAssociations were tested between plasma NfL and brain A beta, medial temporal lobe atrophy (MTA) as well as neuroimaging features of CSVD, including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds. ResultsWe found that participants with either MTA (defined as MTA score >= 2; neurodegeneration [N]+WMH-) or WMH (cut-off for log-transformed WMH volume at 50th percentile; N-WMH+) manifested increased plasma NfL levels. Participants with both pathologies (N+WMH+) showed the highest NfL compared to N+WMH-, N-WMH+, and N-WMH- individuals. DiscussionPlasma NfL has potential utility in stratifying individual and combined contributions of AD pathology and CSVD to cognitive impairment.
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| 21. |
- Eckernäs, Emma, 1992, et al.
(författare)
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N,N-dimethyltryptamine affects electroencephalography response in a concentration-dependent manner-A pharmacokinetic/pharmacodynamic analysis
- 2023
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Ingår i: Cpt-Pharmacometrics & Systems Pharmacology. - : Wiley. - 2163-8306. ; 12:4, s. 474-486
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Tidskriftsartikel (refereegranskat)abstract
- N,N-dimethyltryptamine (DMT) is a psychedelic substance and is being used as a research tool in investigations of the neurobiology behind the human consciousness using different brain imaging techniques. The effects of psychedelics have commonly been studied using electroencephalography (EEG) and have been shown to produce suppression of alpha power and increase in signal diversity. However, the relationship between DMT exposure and its EEG effects has never been quantified. In this work, a population pharmacokinetic/pharmacodynamic analysis was performed investigating the relationship between DMT plasma concentrations and its EEG effects. Data were obtained from a clinical study where DMT was administered by intravenous bolus dose to 13 healthy subjects. The effects on alpha power, beta power, and Lempel-Ziv complexity were evaluated. DMT was shown to fully suppress alpha power. Beta power was only partially suppressed, whereas an increase in Lempel-Ziv complexity was observed. The relationship between plasma concentrations and effects were described using effect compartment models with sigmoidal maximum inhibitory response or maximum stimulatory response models. Values of the concentration needed to reach half of the maximum response (EC50,e) were estimated at 71, 137, and 54 nM for alpha, beta, and Lempel-Ziv complexity, respectively. A large amount of between-subject variability was associated with both beta power and Lempel-Ziv complexity with coefficients of variability of 75% and 77% for the corresponding EC50,e values, respectively. Alpha power appeared to be the most robust response, with a between-subject variability in EC50,e of 29%. Having a deeper understanding of these processes might prove beneficial in choosing appropriate doses and response biomarkers in the future clinical development of DMT.
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| 22. |
- Eckernäs, Emma, 1992, et al.
(författare)
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Optimized infusion rates for N,N-dimethyltryptamine to achieve a target psychedelic intensity based on a modeling and simulation framework
- 2023
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Ingår i: Cpt-Pharmacometrics & Systems Pharmacology. - 2163-8306. ; 12:10, s. 1398-1410
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Tidskriftsartikel (refereegranskat)abstract
- N,N-dimethyltryptamine (DMT) is a psychedelic compound that is being studied as a therapeutic option in various psychiatric disorders. Due to its short half-life, continuous infusion of DMT has been proposed to extend the psychedelic experience and potential therapeutic effects. The primary aim of this work was to design an infusion protocol for DMT based on a desired level of psychedelic intensity using population pharmacokinetic/pharmacodynamic modeling. As a secondary aim, the impact of choosing a continuous variable or a bounded integer pharmacokinetic/pharmacodynamic model to inform such an infusion protocol was investigated. A previously published continuous variable model and two newly developed bounded integer models were used to assess optimal doses for achieving a target response. Simulations were performed to identify an optimal combination of a bolus dose and an infusion rate. Based on the simulations, optimal doses to achieve intensity ratings between 7 and 9 (possible range = 0-10) were a bolus dose of 16 mg DMT fumarate followed by an infusion rate of 1.4 mg/min based on the continuous variable model and 14 mg with 1.2 mg/min for the two bounded integer models. However, the proportion within target was low (<53%) for all models, indicating that individual dose adjustments would be necessary. Furthermore, some differences between the models were observed. The bounded integer models generally predicted lower proportions within a target of 7-9 with higher proportions exceeding target compared with the continuous variable model. However, results varied depending on target response with the major differences observed at the boundaries of the scale.
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| 23. |
- Eckernäs, Emma, 1992, et al.
(författare)
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Population pharmacokinetic/pharmacodynamic modeling of the psychedelic experience induced by N,N-dimethyltryptamine - Implications for dose considerations
- 2022
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Ingår i: Cts-Clinical and Translational Science. - : Wiley. - 1752-8054 .- 1752-8062. ; 15:12, s. 2928-2937
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Tidskriftsartikel (refereegranskat)abstract
- N,N-dimethyltryptamine (DMT) is a psychedelic compound that is believed to have potential as a therapeutic option in several psychiatric disorders. The number of clinical investigations with DMT is increasing. However, very little is known about the pharmacokinetic properties of DMT as well as any relationship between its exposure and effects. This study aimed to characterize population pharmacokinetics of DMT as well as the relationship between DMT plasma concentrations and its psychedelic effects as measured through subjective intensity ratings. Data were obtained from 13 healthy subjects after intravenous administration of DMT. The data were analyzed using nonlinear mixed-effects modeling in NONMEM. DMT plasma concentrations were described by a two-compartment model with first-order elimination leading to formation of the major metabolite indole 3-acetic acid. The relationship between plasma concentrations and psychedelic intensity was described by an effect site compartment model with a sigmoid maximum effect (E-max) response. DMT clearance was estimated at 26 L/min, a high value indicating elimination of DMT to be independent of blood flow. Higher concentrations of DMT were associated with a more intense experience with the concentration of DMT at the effect site required to produce half of the maximum response estimated at 95 nM. The maximum achievable intensity rating was 10 and the simulated median maximum rating was zero, 2, 4, 8, and 9 after doses of 1, 4, 7, 14, and 20 mg, respectively. The model can be useful in predicting suitable doses for clinical investigations of DMT based on the desired intensity of the subjective experience.
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| 24. |
- Gonzalez-Ortiz, Fernando, et al.
(författare)
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A novel ultrasensitive assay for plasma p-tau217: Performance in individuals with subjective cognitive decline and early Alzheimer's disease.
- 2024
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279. ; 20:2, s. 1239-1249
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Tidskriftsartikel (refereegranskat)abstract
- Detection of Alzheimer's disease (AD) pathophysiology among individuals with mild cognitive changesand those experiencing subjective cognitive decline (SCD) remains challenging. Plasma phosphorylated tau 217 (p-tau217) is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited.We employed a novel p-tau217 immunoassay (University of Gothenburg [UGOT] p-tau217) in four independent cohorts (n=308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired (CU) and mild cognitively impaired (MCI) participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (Barcelonaβeta Brain Research Center's Alzheimer's At-Risk Cohort [β-AARC]).UGOT p-tau217 showed high accuracy (area under the curve [AUC]=0.80-0.91) identifying amyloid beta (Aβ) pathology, determined either by Aβ positron emission tomography or CSF Aβ42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aβ42/40 ratio (AUC=0.91).UGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.
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| 25. |
- Gonzalez-Ortiz, Fernando, et al.
(författare)
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A novel ultrasensitive assay for plasma p-tau217: performance in individuals with subjective cognitive decline and early Alzheimer's disease.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Detection of Alzheimer's disease (AD) pathophysiology among cognitively unimpaired individuals and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma p-tau217 is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited.We employed a novel p-tau217 immunoassay (UGOT p-tau217) in four independent cohorts (n=308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (β-AARC).UGOT p-tau217 showed high accuracy (AUC= 0.80-0.91) identifying Aβ pathology, determined either by Aβ positron emission tomography or CSF Aβ42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aβ42/40 ratio (AUC= 0.91).UGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.
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| 26. |
- Hall, C. Michael, et al.
(författare)
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Second home tourism and climate change
- 2023
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Ingår i: Second Homes and Climate Change. - : Routledge. - 9781003091295 - 9780367549466 - 9781000905533 ; , s. 1-15
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Bokkapitel (refereegranskat)abstract
- The chapter provides an introduction to issues associated with the relationship between second homes and climate change. A major problem identified in existing research is the lack of consistent definitions of what constitutes a second home within and between jurisdictions, which makes comparative research difficult. Existing research is geographically limited in scope although recognition of the environmental impacts of climate change has existed for many years although research on climate change related issues is much more recent. Two major strands of research exist. The first is the contribution of second homes to climate change, which is primarily the use of transport to access second homes. Private cars are identified as the major transport mode for domestic second home tourism. The second strand of research is the impacts of climate change and climate change related events on second home destinations. The latter reflects the majority of contributions to the present work.
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| 27. |
- Kac, Przemyslaw R., et al.
(författare)
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Plasma p-tau212: antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Thereafter, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n=388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202/205. These findings support plasma p-tau212 as a novel peripherally accessible biomarker of AD pathophysiology.
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| 28. |
- Kac, Przemyslaw R., 1995, et al.
(författare)
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Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology.
- 2024
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Ingår i: Nature communications. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Here, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n=388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202/205. These findings support plasma p-tau212 as a peripherally accessible biomarker of AD pathophysiology.
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| 29. |
- Meyer, Pierre-François, et al.
(författare)
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Plasma p-tau231, p-tau181, PET Biomarkers, and Cognitive Change in Older Adults.
- 2022
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Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 91:4, s. 548-560
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate novel plasma p-tau231 and p-tau181, as well as Aβ40 and Aβ42 assays as indicators of tau and Aβ pathologies measured with positron emission tomography (PET), and their association with cognitive change, in cognitively unimpaired older adults.In a cohort of 244 older adults at risk of Alzheimer's disease (AD) owing to a family history of AD dementia, we measured single molecule array (Simoa)-based plasma tau biomarkers (p-tau231 and p-tau181), Aβ40 and Aβ42 with immunoprecipitation mass spectrometry, and Simoa neurofilament light (NfL). A subset of 129 participants underwent amyloid-β (18 F-NAV4694) and tau (18 F-flortaucipir) PET assessments. We investigated plasma biomarker associations with Aβ and tau PET at the global and voxel level and tested plasma biomarker combinations for improved detection of Aβ-PET positivity. We also investigated associations with 8-year cognitive change.Plasma p-tau biomarkers correlated with flortaucipir binding in medial temporal, parietal, and inferior temporal regions. P-tau231 showed further associations in lateral parietal and occipital cortices. Plasma Aβ42/40 explained more variance in global Aβ-PET binding than Aβ42 alone. P-tau231 also showed strong and widespread associations with cortical Aβ-PET binding. Combining Aβ42/40 with p-tau231 or p-tau181 allowed for good distinction between Aβ-negative and -positive participants (area under the receiver operating characteristic curve [AUC] range=0.81-0.86). Individuals with low plasma Aβ42/40 and high p-tau experienced faster cognitive decline.Plasma p-tau231 showed more robust associations with PET biomarkers than p-tau181 in presymptomatic individuals. The combination of p-tau and Aβ42/40 biomarkers detected early AD pathology and cognitive decline. Such markers could be used as prescreening tools to reduce the cost of prevention trials. ANN NEUROL 2022.
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| 30. |
-
Second Homes and Climate Change
- 2023
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- This book is the first to address the important interrelationship between second homes and climate change, which has become an increasingly relevant issue for many regions around the world.Second homes are often a key source of tourist visitation as well as economic benefit for their host communities. The chapters provide an array of international case studies and climate change impacts, including the changing biocultural landscapes in Italy, hazard risks in the mountains of Poland, and the shifting media discussion on second homes and climate change in Finland. Topics covered focus on issues around planning and governance in second home locations, adaptation and mitigation measures implemented by second home owners, and the influence of second home owners’ place attachment in relation to second home impacts. It introduces the overall topic of second homes and climate change while also laying the groundwork for future work in this burgeoning area of research.This book will be of significant interest to upper-level undergraduates, graduate students, and academics in the fields of geography, tourism, planning, housing studies, regional development, environmental management, and disaster management. It would also be of use for professionals who engage with second home communities, particularly planners, government officials, and environmental officers.
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| 31. |
- Tanaka, Tomotaka, et al.
(författare)
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Head-to-head comparison of amplified plasmonic exosome Aβ42 platform and single-molecule array immunoassay in a memory clinic cohort
- 2021
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 28:5, s. 1479-1489
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Various blood biomarkers reflecting brain amyloid-β (Aβ) load have recently been proposed with promising results. However, to date, no comparative study amongst blood biomarkers has been reported. Our objective was to examine the diagnostic performance and cost effectiveness of three blood biomarkers on the same cohort. Methods: Using the same cohort (n = 68), the performances of the single-molecule array (Simoa) Aβ40, Aβ42, Aβ42/Aβ40 and the amplified plasmonic exosome (APEX) Aβ42 blood biomarkers were compared using amyloid positron emission tomography (PET) as the reference standard. The extent to which these blood tests can reduce the recruitment cost of clinical trials was also determined by identifying amyloid positive (Aβ+) participants. Results: Compared to Simoa biomarkers, APEX-Aβ42 showed significantly higher correlations with amyloid PET retention values and excellent diagnostic performance (sensitivity 100%, specificity 93.3%, area under the curve 0.995). When utilized for clinical trial recruitment, our simulation showed that pre-screening with blood biomarkers followed by a confirmatory amyloid PET imaging would roughly half the cost (56.8% reduction for APEX-Aβ42 and 48.6% for Simoa-Aβ42/Aβ40) compared to the situation where only PET imaging is used. Moreover, with 100% sensitivity, APEX-Aβ42 pre-screening does not increase the required number of initial participants. Conclusions: With its high diagnostic performance, APEX is an ideal candidate for Aβ+ subject identification, monitoring and primary care screening, and could efficiently enrich clinical trials with Aβ+ participants whilst halving recruitment costs.
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| 32. |
- Thielmann, Isabel, et al.
(författare)
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The HEXACO-100 Across 16 Languages : A Large-Scale Test of Measurement Invariance
- 2020
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Ingår i: Journal of Personality Assessment. - : Informa UK Limited. - 0022-3891 .- 1532-7752. ; 102:5, s. 714-726
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Tidskriftsartikel (refereegranskat)abstract
- The HEXACO Personality Inventory-Revised (HEXACO-PI-R) has become one of the most heavily applied measurement tools for the assessment of basic personality traits. Correspondingly, the inventory has been translated to many languages for use in cross-cultural research. However, formal tests examining whether the different language versions of the HEXACO-PI-R provide equivalent measures of the 6 personality dimensions are missing. We provide a large-scale test of measurement invariance of the 100-item version of the HEXACO-PI-R across 16 languages spoken in European and Asian countries (N = 30,484). Multigroup exploratory structural equation modeling and confirmatory factor analyses revealed consistent support for configural and metric invariance, thus implying that the factor structure of the HEXACO dimensions as well as the meaning of the latent HEXACO factors is comparable across languages. However, analyses did not show overall support for scalar invariance; that is, equivalence of facet intercepts. A complementary alignment analysis supported this pattern, but also revealed substantial heterogeneity in the level of (non)invariance across facets and factors. Overall, results imply that the HEXACO-PI-R provides largely comparable measurement of the HEXACO dimensions, although the lack of scalar invariance highlights the necessity for future research clarifying the interpretation of mean-level trait differences across countries.
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