| 1. |
- Vogel, Jacob W., et al.
(author)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 2. |
- Brigham-Grette, Julie, et al.
(author)
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Pliocene warmth, polar amplification, and stepped pleistocene cooling recorded in NE arctic russia
- 2013
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In: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 340:6139, s. 1421-1427
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Journal article (peer-reviewed)abstract
- Understanding the evolution of Arctic polar climate from the protracted warmth of the middle Pliocene into the earliest glacial cycles in the Northern Hemisphere has been hindered by the lack of continuous, highly resolved Arctic time series. Evidence from Lake El'gygytgyn, in northeast (NE) Arctic Russia, shows that 3.6 to 3.4 million years ago, summer temperatures were similar to 8 degrees C warmer than today, when the partial pressure of CO2 was similar to 400 parts per million. Multiproxy evidence suggests extreme warmth and polar amplification during the middle Pliocene, sudden stepped cooling events during the Pliocene-Pleistocene transition, and warmer than present Arctic summers until similar to 2.2 million years ago, after the onset of Northern Hemispheric glaciation. Our data are consistent with sea-level records and other proxies indicating that Arctic cooling was insufficient to support large-scale ice sheets until the early Pleistocene.
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| 3. |
- Ek, Kristine, 1975, et al.
(author)
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A harmonized method for automatable life cycle sustainability performance assessment and comparison of civil engineering works design concepts
- 2020
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In: IOP Conference Series: Earth and Environmental Science. - : IOP Publishing. - 1755-1307 .- 1755-1315. ; 588:5
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Conference paper (peer-reviewed)abstract
- The life cycle sustainability performance of civil engineering works is increasingly important. The possibility to influence the sustainability of a project design is larger in the conceptual stage than in later stages. Better-informed decisions regarding design choices’ impact on sustainability can be made by comparing conceptual project designs based on an assessment of their life cycle sustainability performance. It is essential that concepts are assessed in a harmonized way and compared impartially. Current standards provide the general framework for the assessment of sustainability performance, but do not give detailed guidance on calculation of sustainability indicators and their aggregation. Since design in automated systems is becoming increasingly common, there is a growing need for machine-readable data and automatable assessment methods. Assessment methods which can be applied using open-access data is important to achieve fair competition. This paper aims to provide a method for life cycle sustainability performance assessment and comparison of civil engineering works design concepts, possible to apply using open-access Environmental Product Declarations (EPDs) and life cycle assessment (LCA) data. The purpose is to enable fair and automatable sustainability assessments of design concepts, to facilitate impartial comparisons of such assessments as a basis for choosing sustainable designs. A literature review of relevant standards and scientific papers on sustainability assessment of construction and civil engineering works was performed. A harmonized, fair and automatable method for life cycle sustainability assessment and comparison of civil engineering works design concepts, well-suited for optimization purposes, is presented. However, the aim currently limits categories and indicators possible to include. The proposed method includes guidance on the calculation of environmental, social and economic indicators, based on LCA, life cycle costing (LCC) and external costs, and aggregation using normalisation and weighting factors of the Product Environmental Footprint (PEF). The proposed method allows for an impartial comparison of the sustainability of design concepts, resulting in better-informed decisions.
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| 4. |
- Eriksson, Anders, et al.
(author)
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Layer Formation by Resputtering in Ti-Si-C Hard Coatings during Large Scale Cathodic Arc Deposition
- 2011
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In: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 205:15, s. 3923-3930
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Journal article (peer-reviewed)abstract
- This paper presents the physical mechanism behind the phenomenon of self-layering in thin films made by industrial scale cathodic arc deposition systems using compound cathodes and rotating substrate fixture. For Ti-Si-C films, electron microscopy and energy dispersive x-ray spectrometry reveals a trapezoid modulation in Si content in the substrate normal direction, with a period of 4 to 23 nm dependent on cathode configuration. This is caused by preferential resputtering of Si by the energetic deposition flux incident at high incidence angles when the substrates are facing away from the cathodes. The Ti-rich sub-layers exhibit TiC grains with size up to 5 nm, while layers with high Si-content are less crystalline. The nanoindentation hardness of the films increases with decreasing layer thickness.
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| 5. |
- Eriksson, Anders, et al.
(author)
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Ti-Si-C-N Thin Films Grown by Reactive Arc Evaporation from Ti3SiC2 Cathodes
- 2011
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In: Journal of Materials Research. - : Cambrdige University Press. - 0884-2914 .- 2044-5326. ; 26, s. 874-881
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Journal article (peer-reviewed)abstract
- Ti-Si-C-N thin films were deposited onto WC-Co substrates by industrial scale arc evaporation from Ti3SiC2 compound cathodes in N2 gas. Microstructure and hardness were found to be highly dependent on the wide range of film compositions attained, comprising up to 12 at.% Si and 16 at.% C. Nonreactive deposition yielded films consisting of understoichiometric TiCx, Ti and silicide phases with high (27 GPa) hardness. At a nitrogen pressure of 0.25-0.5 Pa, below that required for N saturation, superhard, 45-50 GPa, (Ti,Si)(C,N) films with a nanocrystalline feathered structure were formed. Films grown above 2 Pa displayed crystalline phases of more pronounced nitride character, but with C and Si segregated to grain boundaries to form weak grain boundary phases. In abundance of N, the combined presence of Si and C disturb cubic phase growth severely and compromises the mechanical strength of the films.
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| 6. |
- Galien, Sarah, et al.
(author)
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Point of care ultrasound screening for deep vein thrombosis in critically ill COVID-19 patients, an observational study
- 2021
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In: Thrombosis Journal. - : Springer Science and Business Media LLC. - 1477-9560. ; 19:1
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Journal article (peer-reviewed)abstract
- BackgroundDeep vein thrombosis (DVT) is common in critically ill patients with Coronavirus disease 2019 (COVID-19) and may cause fatal pulmonary embolism (PE) prior to diagnosis due to subtle clinical symptoms. The aim of this study was to explore the feasibility of bedside screening for DVT in critically ill COVID-19 patients performed by physicians with limited experience of venous ultrasound. We further aimed to compare inflammation, coagulation and organ dysfunction in patients with and without venous thromboembolism (VTE).MethodsThis observational study included patients with COVID-19 admitted to the intensive care unit (ICU) of a tertiary hospital in Sweden and screened for DVT with proximal compression ultrasound of the lower extremities between April and July 2020. Screening was performed by ICU residents having received a short online education and one hands-on-session. Pathological screening ultrasound was confirmed by formal ultrasound whereas patients with negative screening underwent formal ultrasound on clinical suspicion. Clinical data, laboratory findings and follow-up were extracted from medical records.ResultsOf 90 eligible patients, 56 were screened by seven ICU residents with no (n = 5) or limited (n = 2) previous experience of DVT ultrasound who performed a median of 4 (IQR 2–19) examinations. Four (7.1%) patients had pathological screening ultrasound of which three (5.6%) were confirmed by formal ultrasound. None of the 52 patients with negative screening ultrasound were diagnosed with DVT during follow-up. Six patients were diagnosed with PE of which four prior to negative screening and two following negative and positive screening respectively. Patients with VTE (n = 8) had higher median peak D-dimer (24.0 (IQR 14.2–50.5) vs. 2.8 (IQR 1.7–7.2) mg/L, p = 0.004), mean peak C-reactive protein (363 (SD 80) vs. 285 (SD 108) mg/L, p = 0.033) and median peak plasma creatinine (288 (IQR 131–328) vs. 94 (IQR 78–131) μmol/L, p = 0.009) compared to patients without VTE (n = 48). Five patients (63%) with VTE received continuous renal replacement therapy compared to six patients (13%) without VTE (p = 0.005).ConclusionICU residents with no or limited experience could detect DVT with ultrasound in critically ill COVID-19 patients following a short education. VTE was associated with kidney dysfunction and features of hyperinflammation and hypercoagulation.Trial registrationClinicalTrials ID: NCT04316884. Registered 20 March 2020.
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| 7. |
- Groot, Colin, et al.
(author)
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Latent atrophy factors related to phenotypical variants of posterior cortical atrophy
- 2020
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In: Neurology. - 1526-632X. ; 95:12, s. 1672-1685
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine whether atrophy relates to phenotypical variants of posterior cortical atrophy (PCA) recently proposed in clinical criteria (i.e., dorsal, ventral, dominant-parietal, and caudal) we assessed associations between latent atrophy factors and cognition. METHODS: We employed a data-driven Bayesian modeling framework based on latent Dirichlet allocation to identify latent atrophy factors in a multicenter cohort of 119 individuals with PCA (age 64 ± 7 years, 38% male, Mini-Mental State Examination 21 ± 5, 71% β-amyloid positive, 29% β-amyloid status unknown). The model uses standardized gray matter density images as input (adjusted for age, sex, intracranial volume, MRI scanner field strength, and whole-brain gray matter volume) and provides voxelwise probabilistic maps for a predetermined number of atrophy factors, allowing every individual to express each factor to a degree without a priori classification. Individual factor expressions were correlated to 4 PCA-specific cognitive domains (object perception, space perception, nonvisual/parietal functions, and primary visual processing) using general linear models. RESULTS: The model revealed 4 distinct yet partially overlapping atrophy factors: right-dorsal, right-ventral, left-ventral, and limbic. We found that object perception and primary visual processing were associated with atrophy that predominantly reflects the right-ventral factor. Furthermore, space perception was associated with atrophy that predominantly represents the right-dorsal and right-ventral factors. However, individual participant profiles revealed that the large majority expressed multiple atrophy factors and had mixed clinical profiles with impairments across multiple domains, rather than displaying a discrete clinical-radiologic phenotype. CONCLUSION: Our results indicate that specific brain behavior networks are vulnerable in PCA, but most individuals display a constellation of affected brain regions and symptoms, indicating that classification into 4 mutually exclusive variants is unlikely to be clinically useful.
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| 8. |
- Holmqvist, Jacob, et al.
(author)
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Cardiac dysfunction and mortality in critically ill patients with COVID-19: A Swedish multicentre observational study
- 2022
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 66:5, s. 606-614
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Journal article (peer-reviewed)abstract
- Background The prevalence and importance of cardiac dysfunction in critically ill patients with COVID-19 in Sweden is not yet established. The aim of the study was to assess the prevalence of cardiac dysfunction and elevated pulmonary artery pressure (PAP), and its influence on mortality in patients with COVID-19 in intensive care in Sweden. Methods This was a multicentre observational study performed in five intensive care units (ICUs) in Sweden. Patients admitted to participating ICU with COVID-19 were examined with echocardiography within 72 h from admission and again after 4 to 7 days. Cardiac dysfunction was defined as left ventricular (LV) dysfunction (ejection fraction <50% and/or regional hypokinesia) or right ventricular (RV) dysfunction (defined as TAPSE <17 mm or visually assessed moderate/severe RV dysfunction). Results We included 132 patients, of whom 127 (96%) were intubated. Cardiac dysfunction was found in 42 (32%) patients. Most patients had cardiac dysfunction at the first assessment (n = 35) while a few developed cardiac dysfunction later (n = 7) and some changed type of dysfunction (n = 3). LV dysfunction was found in 21 and RV dysfunction in 19 patients, while 5 patients had combined dysfunction. Elevated PAP was found in 34 patients (26%) and was more common in patients with RV dysfunction. RV dysfunction and elevated PAP were independently associated with an increased risk of death (OR 3.98, p = .013 and OR 3.88, p = .007, respectively). Conclusions Cardiac dysfunction occurs commonly in critically ill patients with COVID-19 in Sweden. RV dysfunction and elevated PAP are associated with an increased risk of death.
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| 9. |
- Kagan, Jacob, et al.
(author)
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National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level : Interrogation of Premalignant Lesions
- 2020
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 19:5, s. 1900-1912
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Journal article (peer-reviewed)abstract
- A Think-Tank Meeting was convened by the National Cancer Institute (NCI) to solicit experts' opinion on the development and application of multiomic single-cell analyses, and especially single-cell proteomics, to improve the development of a new generation of biomarkers for cancer risk, early detection, diagnosis, and prognosis as well as to discuss the discovery of new targets for prevention and therapy. It is anticipated that such markers and targets will be based on cellular, subcellular, molecular, and functional aberrations within the lesion and within individual cells. Single-cell proteomic data will be essential for the establishment of new tools with searchable and scalable features that indude spatial and temporal cartographies of premalignant and malignant lesions. Challenges and potential solutions that were discussed included (i) The best way/s to analyze single-cells from fresh and preserved tissue; (ii) Detection and analysis of secreted molecules and from single cells, especially from a tissue slice; (iii) Detection of new, previously undocumented cell type/s in the premalignant and early stage cancer tissue microenvironment; (iv) Multiomic integration of data to support and inform proteomic measurements; (v) Subcellular organelles-identifying abnormal structure, function, distribution, and location within individual premalignant and malignant cells; (vi) How to improve the dynamic range of single-cell proteomic measurements for discovery of differentially expressed proteins and their post-translational modifications (PTM); (vii) The depth of coverage measured concurrently using single-cell techniques; (viii) Quantitation - absolute or semiquantitative? (ix) Single methodology or multiplexed combinations? (x) Application of analytical methods for identification of biologically significant subsets; (xi) Data visualization of N-dimensional data sets; (xii) How to construct intercellular signaling networks in individual cells within premalignant tumor microenvironments (TME); (xiii) Associations between intrinsic cellular processes and extrinsic stimuli; (xiv) How to predict cellular responses to stress-inducing stimuli; (xv) Identification of new markers for prediction of progression from precursor, benign, and localized lesions to invasive cancer, based on spatial and temporal changes within individual cells; (xvi) Identification of new targets for immunoprevention or immunotherapy-identification of neoantigens and surfactome of individual cells within a lesion.
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