| 1. |
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| 2. |
- de Rojas, I., et al.
(author)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 3. |
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| 4. |
- Polettini, M., et al.
(author)
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Decay studies in the A∼225 Po-Fr region from the DESPEC campaign at GSI in 2021
- 2022
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In: Il Nuovo Cimento. - : Società Italiana di Fisica. - 2037-4909. ; 45:5
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Journal article (peer-reviewed)abstract
- The HISPEC-DESPEC collaboration aims at investigating the structure of exotic nuclei formed in fragmentation reactions with decay spectroscopy measurements, as part of the FAIR Phase-0 campaign at GSI. This paper reports on first results of an experiment performed in spring 2021, with a focus on beta-decaystudies in the Po-Fr nuclei in the 220 < A <230 island of octupole deformation exploiting the DESPEC setup. Ion-beta correlations and fast-timing techniques are being employed, giving an insight into this difficult-to-reach region.
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| 5. |
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| 6. |
- Wightman, D. P., et al.
(author)
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A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
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Journal article (peer-reviewed)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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| 7. |
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| 8. |
- Dyer, A. H., et al.
(author)
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Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD
- 2020
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In: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610. ; 21:2, s. 194-200
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Journal article (peer-reviewed)abstract
- Objective: Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD. Design: This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates. Setting and Participants: 448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries. Results: Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (beta = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates. Conclusions and Implications: This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD. (C) 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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| 9. |
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| 10. |
- Kern, R., et al.
(author)
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Restoring the valence-shell stabilization in Nd 140
- 2020
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In: Physical Review C. - 2469-9985. ; 102:4
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Journal article (peer-reviewed)abstract
- A projectile Coulomb-excitation experiment was performed at the radioactive-ion beam facility HIE-ISOLDE at CERN to obtain E2 and M1 transition matrix elements of Nd140 using the multistep Coulomb-excitation code gosia. The absolute M1 strengths, B(M1;22+→21+)=0.033(8)μN2,B(M1;23+→21+)=0.26-0.10+0.11μN2, and B(M1;24+→21+)<0.04μN2, identify the 23+ state as the main fragment of the one-quadrupole-phonon proton-neutron mixed-symmetry state of Nd140. The degree of F-spin mixing in Nd140 was quantified with the determination of the mixing matrix element VF-mix<7-7+13keV.
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| 11. |
- Budeus, B., et al.
(author)
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Human cord blood b cells differ from the adult counterpart by conserved ig repertoires and accelerated response dynamics
- 2021
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 206:12, s. 2839-2851
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Journal article (peer-reviewed)abstract
- Neonatal and infant immune responses are characterized by a limited capability to generate protective Ab titers and memory B cells as seen in adults. Multiple studies support an immature or even impaired character of umbilical cord blood (UCB) B cells themselves. In this study, we provide a comprehensive molecular and functional comparison of B cell subsets from UCB and adult peripheral blood. Most UCB B cells have a mature, naive B cell phenotype as seen in adults. The UCB Ig repertoire is highly variable but interindividually conserved, as BCR clonotypes are frequently shared between neonates. Furthermore, UCB B cells show a distinct transcriptional program that confers accelerated responsiveness to stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into Ab-secreting cells, presumably limiting memory B cell formation. Humanized mice suggest that the distinctness of UCB versus adult B cells is already reflected by the developmental program of hematopoietic precursors, arguing for a layered B-1/B-2 lineage system as in mice, albeit our findings suggest only partial comparability to murine B-1 cells. Our study shows that UCB B cells are not immature or impaired but differ from their adult mature counterpart in a conserved BCR repertoire, efficient IgA class switching, and accelerated, likely transient response dynamics. © 2021 by TheAmericanAssociation of Immunologists, Inc.
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| 12. |
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| 13. |
- Bethlehem, RAI, et al.
(author)
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Brain charts for the human lifespan
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
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Journal article (peer-reviewed)abstract
- Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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| 14. |
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| 15. |
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| 16. |
- Chng, Kern Rei, et al.
(author)
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Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
- 2020
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 941-951
-
Journal article (peer-reviewed)abstract
- Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.
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| 17. |
- Danko, David, et al.
(author)
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A global metagenomic map of urban microbiomes and antimicrobial resistance
- 2021
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In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 184:13, s. 3376-3393
-
Journal article (peer-reviewed)abstract
- We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
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| 18. |
- Lauterbur, M. Elise, et al.
(author)
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Expanding the stdpopsim species catalog, and lessons learned for realistic genome simulations
- 2023
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In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 12
-
Journal article (peer-reviewed)abstract
- Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic datasets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than threefold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed the best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Fortarezza, F, et al.
(author)
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COVID-19 Pulmonary Pathology: The Experience of European Pulmonary Pathologists throughout the First Two Waves of the Pandemic
- 2022
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In: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 12:1
-
Journal article (peer-reviewed)abstract
- Autoptic studies of patients who died from COVID-19 constitute an important step forward in improving our knowledge in the pathophysiology of SARS-CoV-2 infection. Systematic analyses of lung tissue, the organ primarily targeted by the disease, were mostly performed during the first wave of the pandemic. Analyses of pathological lesions at different times offer a good opportunity to better understand the disease and how its evolution has been influenced mostly by new SARS-CoV-2 variants or the different therapeutic approaches. In this short report we summarize responses collected from a questionnaire survey that investigated important pathological data during the first two pandemic waves (spring-summer 2020; autumn-winter 2020–2021). The survey was submitted to expert lung pathologists from nine European countries involved in autoptic procedures in both pandemic waves. The frequency of each lung lesion was quite heterogeneous among the participants. However, a higher frequency of pulmonary superinfections, both bacterial and especially fungal, was observed in the second wave compared to the first. Obtaining a deeper knowledge of the pathological lesions at the basis of this complex and severe disease, which change over time, is crucial for correct patient management and treatment. Autoptic examination is a useful tool to achieve this goal.
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| 23. |
- Jansen, Iris E, et al.
(author)
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Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- 2022
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In: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842
-
Journal article (peer-reviewed)abstract
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
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| 24. |
- Keable, Stephen M., et al.
(author)
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Room temperature XFEL crystallography reveals asymmetry in the vicinity of the two phylloquinones in photosystem I
- 2021
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- Photosystem I (PS I) has a symmetric structure with two highly similar branches of pigments at the center that are involved in electron transfer, but shows very different efficiency along the two branches. We have determined the structure of cyanobacterial PS I at room temperature (RT) using femtosecond X-ray pulses from an X-ray free electron laser (XFEL) that shows a clear expansion of the entire protein complex in the direction of the membrane plane, when compared to previous cryogenic structures. This trend was observed by complementary datasets taken at multiple XFEL beamlines. In the RT structure of PS I, we also observe conformational differences between the two branches in the reaction center around the secondary electron acceptors A1A and A1B. The π-stacked Phe residues are rotated with a more parallel orientation in the A-branch and an almost perpendicular confirmation in the B-branch, and the symmetry breaking PsaB-Trp673 is tilted and further away from A1A. These changes increase the asymmetry between the branches and may provide insights into the preferential directionality of electron transfer.
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| 25. |
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| 26. |
- Kern, Marius, et al.
(author)
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Integration of X-ray radiography and automated mineralogy data for the optimization of ore sorting routines
- 2022
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In: Minerals Engineering. - : Elsevier. - 0892-6875 .- 1872-9444. ; 186
-
Journal article (peer-reviewed)abstract
- X-ray transmission sorting is arguably the most successful ore sorting technique used in the mining industry today. In order to establish the suitability of X-ray transmission sorting for a specific ore deposit or raw material type, the current state of the art involves time-consuming and costly empirical testing. In this paper, we show how the success of X-ray transmission sorting can be reliably predicted based on X-ray radiographs that are quick and inexpensive to obtain for a large number of samples. We document this novel approach using a large suite of samples of scheelite ores from the Mittersill deposit in Austria. Using only the X-ray radiographs at a spatial resolution of 0.12 mm we quantify the volume of high-density scheelite at different spatial resolution. The results are compared to and validated by data obtained by computer tomography and scanning electron microscopy-based image analysis. The X-ray radiograph data set is then down sampled to spatial resolutions of 0.8 mm, 3.2 mm, 12 mm and 24 mm in order to gauge the optimum spatial resolution prior to any empirical testing. Upgrading curves can be calculated, and in combination with quantitative data obtained by complementary analytical methods, the mineralogical and chemical composition of concentrate and waste can be predicted. The workflow can be transferred without any problems to many other ore types with a significant density difference between ore mineral(s) and gangue minerals.
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| 27. |
- Kern, Ralph, et al.
(author)
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Coulomb Excitation of Proton-rich N = 80 Isotones at HIE-ISOLDE
- 2020
-
In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1555:1
-
Journal article (peer-reviewed)abstract
- A projectile Coulomb-excitation experiment was performed at the radioactive ion beam facility HIE-ISOLDE at CERN. The radioactive 140Nd and 142Sm ions were post accelerated to the energy of 4.62 MeV/A and impinged on a 1.45 mg/cm2-thin 208Pb target. The γ rays depopulating the Coulomb-excited states were recorded by the HPGe-array MINIBALL. The scattered charged particles were detected by a double-sided silicon strip detector in forward direction. Experimental γ-ray intensities were used for the determination of electromagnetic transition matrix elements. Preliminary results for the reduced transition strength of the B(M1 23+ to 21+)=0.35(19) μN2 of 140Nd and a first estimation for 142Sm have been deduced using the Coulomb-excitation calculation software GOSIA. The 23+ states of 140Nd and 142Sm show indications of being the main fragment of the proton-neutron mixed-symmetry 21, ms+ state.
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| 28. |
- Kern, Simon, et al.
(author)
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Direct numerical simulations of an airfoil undergoing dynamic stall at different background disturbance levels
- 2024
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In: Journal of Fluid Mechanics. - : Cambridge University Press (CUP). - 0022-1120 .- 1469-7645. ; 986
-
Journal article (peer-reviewed)abstract
- Thin airfoil dynamic stall at moderate Reynolds numbers is typically linked to the sudden bursting of a small laminar separation bubble close to the leading edge. Given the strong sensitivity of laminar separation bubbles to external disturbances, the onset of dynamic stall on a NACA0009 airfoil section subject to different levels of low-amplitude free stream disturbances is investigated using direct numerical simulations. The flow is practically indistinguishable from clean inflow simulations in the literature for turbulence intensities at the leading edge of Tu = 0.02 %. At slightly higher turbulence intensities of Tu = 0.05 %, the bursting process is found to be considerably less smooth and strong coherent vortex shedding from the laminar separation bubble is observed prior to the formation of the dynamic stall vortex (DSV). This phenomenon is considered in more detail by analysing its appearance in an ensemble of simulations comprising statistically independent realisations of the flow, thus proving its statistical relevance. In order to extract the transient dynamics of the vortex shedding, the classical proper orthogonal decomposition method is generalised to include time in the energy measure and applied to the time-resolved simulation data of incipient dynamic stall. Using this technique, the dominant transient spatiotemporally correlated features are distilled and the wave train of the vortex shedding prior to the emergence of the main DSV is reconstructed from the flow data exhibiting dynamics of large-scale coherent growth and decay within the turbulent boundary layer.
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| 29. |
- Kern, S., et al.
(author)
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Reflection-enhanced gain in traveling-wave parametric amplifiers
- 2023
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In: Physical Review B. - 2469-9969 .- 2469-9950. ; 107:17
-
Journal article (peer-reviewed)abstract
- The operating principle of traveling-wave parametric amplifiers is typically understood in terms of the standard coupled mode theory, which describes the evolution of forward propagating waves without any reflections, i.e., for perfect impedance matching. However, in practice, superconducting microwave amplifiers are unmatched nonlinear finite-length devices, where the reflecting waves undergo complex parametric processes, not described by the standard coupled mode theory. Here, we present an analytical solution for the TWPA gain, which includes the interaction of reflected waves. These reflections result in corrections to the well-known results of the standard coupled mode theory, which are obtained for both three-wave and four-wave mixing processes. Due to these reflections, the gain is enhanced and unwanted nonlinear phase modulations are suppressed. Predictions of the model are experimentally demonstrated on two types of unmatched TWPA, based on coplanar waveguides with a central wire consisting of (i) a high kinetic inductance superconductor, and (ii) an array of 2000 Josephson junctions.
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| 30. |
- Kiguchi, Tekeyuki, et al.
(author)
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Out-of-hospital cardiac arrest across the World : First report from the International Liaison Committee on Resuscitation (ILCOR).
- 2020
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In: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 152, s. 39-49
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Journal article (peer-reviewed)abstract
- BACKGROUND: Since development of the Utstein style recommendations for the uniform reporting of cardiac arrest, increasing numbers of national and regional out-of-hospital cardiac arrest (OHCA) registries have been established worldwide. The International Liaison Committee on Resuscitation (ILCOR) created the Research and Registries Working Group and aimed to systematically report data collected from these registries.METHODS: We conducted two surveys of voluntarily participating national and regional registries. The first survey aimed to identify which core elements of the current Utstein style for OHCA were collected by each registry. The second survey collected descriptive summary data from each registry. We chose the data collected for the second survey based on the availability of core elements identified by the first survey.RESULTS: Seven national and four regional registries were included in the first survey and nine national and seven regional registries in the second survey. The estimated annual incidence of emergency medical services (EMS)-treated OHCA was 30.0-97.1 individuals per 100,000 population. The combined data showed the median age varied from 64 to 79 years and more than half were male in all 16 registries. The provision of bystander cardiopulmonary resuscitation (CPR) and bystander automated external defibrillator (AED) use was 19.1-79.0% in all registries and 2.0-37.4% among 11 registries, respectively. Survival to hospital discharge or 30-day survival after EMS-treated OHCA was 3.1-20.4% across all registries. Favorable neurological outcome at hospital discharge or 30 days after EMS-treated OHCA was 2.8-18.2%. Survival to hospital discharge or 30-day survival after bystander-witnessed shockable OHCA ranged from 11.7% to 47.4% and favorable neurological outcome from 9.9% to 33.3%.CONCLUSION: This report from ILCOR describes data on systems of care and outcomes following OHCA from nine national and seven regional registries across the world. We found variation in reported survival outcomes and other core elements of the current Utstein style recommendations for OHCA across nations and regions.
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| 31. |
- Mielke, M. M., et al.
(author)
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Comparison of CSF neurofilament light chain, neurogranin, and tau to MRI markers
- 2021
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 17:5, s. 801-812
-
Journal article (peer-reviewed)abstract
- Introduction We determined whether cerebrospinal fluid (CSF) neurofilament light (NfL), neurogranin (Ng), and total-tau (t-tau) differentially mapped to magnetic resonance imaging (MRI) measures of cortical thickness, microstructural integrity (corpus callosum and cingulum fractional anisotropy [FA]), and white matter hyperintensities (WMH). Methods Analyses included 536 non-demented Mayo Clinic Study of Aging participants with CSF NfL, Ng, t-tau, amyloid beta (A beta)42 and longitudinal MRI scans. Linear mixed models assessed longitudinal associations between CSF markers and MRI changes. Results Higher CSF NfL was associated with decreasing microstructural integrity and WMH. Higher t-tau was associated with decreasing temporal lobe and Alzheimer's disease (AD) meta region of interest (ROI) cortical thickness. There was no association between Ng and any MRI measure. CSF A beta 42 interacted with Ng for declines in temporal lobe and AD meta ROI cortical thickness and cingulum FA. Discussion CSF NfL predicts changes in white matter integrity, t-tau reflects non-specific changes in cortical thickness, and Ng reflects AD-specific synaptic and neuronal degeneration.
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| 32. |
- Montoliu-Gaya, Laia, et al.
(author)
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Mass spectrometric simultaneous quantification of tau species in plasma shows differential associations with amyloid and tau pathologies
- 2023
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In: Nature Aging. - 2662-8465. ; 3:6, s. 661-669
-
Journal article (peer-reviewed)abstract
- Blood phosphorylated tau (p-tau) biomarkers, at differing sites, demonstrate high accuracy to detect Alzheimer & apos;s disease (AD). However, knowledge on the optimal marker for disease identification across the AD continuum and the link to pathology is limited. This is partly due to heterogeneity in analytical methods. In this study, we employed an immunoprecipitation mass spectrometry method to simultaneously quantify six phosphorylated (p-tau181, p-tau199, p-tau202, p-tau205, p-tau217 and p-tau231) and two non-phosphorylated plasma tau peptides in a total of 214 participants from the Paris Lariboisiere and Translational Biomarkers of Aging and Dementia cohorts. Our results indicate that p-tau217, p-tau231 and p-tau205 are the plasma tau forms that best reflect AD-related brain changes, although with distinct emergences along the disease course and correlations with AD features-amyloid and tau. These findings support the differential association of blood p-tau variants with AD pathology, and our method offers a potential tool for disease staging in clinical trials. A mass spectrometric analysis of plasma tau species identifies phosphorylated tau peptides p-tau217, p-tau231 and p-tau205 with distinct correlations with amyloid and tau pathologies and emergences along the AD continuum.
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| 33. |
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| 34. |
- Salvado, G., et al.
(author)
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The protective gene dose effect of the APOE epsilon 2 allele on gray matter volume in cognitively unimpaired individuals
- 2022
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:7, s. 1383-1395
-
Journal article (peer-reviewed)abstract
- Introduction: Harboring two copies of the apolipoprotein E (APOE) epsilon 2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired epsilon 2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of epsilon 2 genotypic groups were compared to each other and to the reference group (APOE epsilon 3/epsilon 3). Results: Carrying at least one epsilon 2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE epsilon 2 homozygotes, but not APOE epsilon 2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-beta deposition, the larger GM volumes in key brain regions may confer APOE epsilon 2 homozygotes additional protection against AD-related cognitive decline.
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| 35. |
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| 36. |
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| 37. |
- Srikrishna, Meera, et al.
(author)
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CT-based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration
- 2024
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In: Alzheimers & Dementia. - 1552-5260. ; 20:1, s. 629-640
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Journal article (peer-reviewed)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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| 38. |
- Staubitz, J. I., et al.
(author)
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EUROCRINE® : Nebennierenoperationen 2015 bis 2019 – überraschende erste Ergebnisse
- 2021
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In: Der Chirurg. - : Springer Science and Business Media LLC. - 0009-4722 .- 1433-0385. ; 92:5, s. 448-463
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Journal article (peer-reviewed)abstract
- Background: Since 2015 operations performed in the field of endocrine surgery have been entered into the European registry EUROCRINE®. The aim of this analysis was a description of the current healthcare situation for adrenal surgery in a homogeneous healthcare environment corresponding to the German-speaking countries—or to the presence of the working group on surgical endocrinology (CAEK) of the German society for general and visceral surgery (DGAV)—and to assess the adherence to current international treatment guidelines. Methods: An analysis of the preoperative diagnostics, the applied operative techniques and the underlying histological entities was carried out for all operations on adrenal glands in Germany, Switzerland and Austria, which were registered in EUROCRINE® from 2015 to 2019. Results: In the total of 21 participating hospitals from the German-speaking EUROCRINE® countries, 658 operations on adrenal glands were performed. In 90% of cases unilateral adrenalectomy was performed, in 3% bilateral adrenalectomy and in 7% other resection procedures. In 41% the main histological diagnosis was an adrenocortical adenoma. In 15% malignant entities were detected on final histology, including 6% adrenocortical carcinoma (ACC) and 8% metastases to the adrenal glands. 23% of the operations were performed for pheochromocytoma. This entity was primarily resected using minimally invasive approaches (82%), whereas minimally invasive techniques were applied in 28% for ACC and in 66% for metastases to the adrenal glands. Conclusion: Surprisingly, following adrenocortical adenoma and pheochromocytoma, the third most common histological entity was metastasis of different extra-adrenal primary tumors to the adrenal gland. Of the operations for ACC 28% were scheduled for minimally invasive techniques, but conversion to open surgery was necessary in 20%. The analysis revealed discrepancies between treatment reality and international guideline recommendations that raise questions, which will be addressed by an updated version of the EUROCRINE® module for the documentation of adrenal surgery.
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| 39. |
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| 40. |
- Wolters, Frank J, et al.
(author)
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Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium.
- 2020
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In: Neurology. - 1526-632X. ; 95:5
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Journal article (peer-reviewed)abstract
- To determine changes in the incidence of dementia between 1988 and 2015.This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex.Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval [CI], 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] vs 8% [0%-15%]).The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations.
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