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1.
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2.
  • Librado, P., et al. (författare)
  • The origins and spread of domestic horses from the Western Eurasian steppes
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 634-640
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region. Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).
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3.
  • Fages, A., et al. (författare)
  • Tracking Five Millennia of Horse Management with Extensive Ancient Genome Time Series
  • 2019
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 177:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (>= 1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modem legacy of past equestrian civilisations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN "speed gene," only rose in popularity within the last millennium. Finally, the development of modem breeding impacted genetic diversity more dramatically than the previous millennia of human management.
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4.
  • Kreibich, H., et al. (författare)
  • Adaptation to flood risk : results of international paired flood event studies
  • 2017
  • Ingår i: Earth's Future. - 2328-4277. ; 5:10, s. 953-965
  • Tidskriftsartikel (refereegranskat)abstract
    • As flood impacts are increasing in large parts of the world, understanding the primary drivers of changes in risk is essential for effective adaptation. To gain more knowledge on the basis of empirical case studies, we analyze eight paired floods, i.e. consecutive flood events that occurred in the same region, with the second flood causing significantly lower damage. These success stories of risk reduction were selected across different socio-economic and hydro-climatic contexts. The potential of societies to adapt is uncovered by describing triggered societal changes, as well as formal measures and spontaneous processes that reduced flood risk. This novel approach has the potential to build the basis for an international data collection and analysis effort to better understand and attribute changes in risk due to hydrological extremes in the framework of the IAHSs Panta Rhei initiative. Across all case studies, we find that lower damage caused by the second event was mainly due to significant reductions in vulnerability, e.g. via raised risk awareness, preparedness and improvements of organizational emergency management. Thus, vulnerability reduction plays an essential role for successful adaptation. Our work shows that there is a high potential to adapt, but there remains the challenge to stimulate measures that reduce vulnerability and risk in periods in which extreme events do not occur.
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5.
  • Damgaard, P. D., et al. (författare)
  • The first horse herders and the impact of early Bronze Age steppe expansions into Asia
  • 2018
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 360:6396
  • Tidskriftsartikel (refereegranskat)abstract
    • The Yamnaya expansions from the western steppe into Europe and Asia during the Early Bronze Age (similar to 3000 BCE) are believed to have brought with them Indo-European languages and possibly horse husbandry. We analyzed 74 ancient whole-genome sequences from across Inner Asia and Anatolia and show that the Botai people associated with the earliest horse husbandry derived from a hunter-gatherer population deeply diverged from the Yamnaya. Our results also suggest distinct migrations bringing West Eurasian ancestry into South Asia before and after, but not at the time of, Yamnaya culture. We find no evidence of steppe ancestry in Bronze Age Anatolia from when Indo-European languages are attested there. Thus, in contrast to Europe, Early Bronze Age Yamnaya-related migrations had limited direct genetic impact in Asia.
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6.
  • Walker, Anthony P, et al. (författare)
  • Horizon 2020 EuPRAXIA design study
  • 2017
  • Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 874:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Horizon 2020 Project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") is preparing a conceptual design report of a highly compact and cost-effective European facility with multi-GeV electron beams using plasma as the acceleration medium. The accelerator facility will be based on a laser and/or a beam driven plasma acceleration approach and will be used for photon science, high-energy physics (HEP) detector tests, and other applications such as compact X-ray sources for medical imaging or material processing. EuPRAXIA started in November 2015 and will deliver the design report in October 2019. EuPRAXIA aims to be included on the ESFRI roadmap in 2020.
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10.
  • Malehmir, Alireza, et al. (författare)
  • Near-Surface Geophysical Characterization of Areas Prone to Natural Hazards : A Review of the Current and Perspective on the Future
  • 2016
  • Ingår i: Advances in Geophysics. - : Elsevier. - 0065-2687 .- 2162-7622. ; 57, s. 51-146
  • Tidskriftsartikel (refereegranskat)abstract
    • Natural hazards such as landslides, floods, rockfalls, earthquakes, volcanic eruptions, sinkholes, and snow avalanches represent potential risks to our infrastructures, properties, and lives. That potential will continue to escalate with current and continued human encroachment into risk areas. With the help of geophysical techniques many of those risks can be better understood and quantified, thereby minimized and at least partly mitigated through accurate, site-specific, and proper planning and engineering. On occasions these hazards simply cannot be avoided, but better characterization and therefore understanding of the subsurface geology and natural processes responsible for the threats is possible through integration of various cost-effective geophysical methods with relevant geotechnical, geomechanical, and hydrogeological methods. With the enhanced characterization possible when geophysics is incorporated into natural hazard analysis, potential risks can be better quantified and remediation plans tuned to minimize the threat most natural hazards present to civilizations. In this article we will first review common geophysical methods that can be and have been utilized in studying natural hazard prone areas, then we provide selected case studies and approaches using predominantly our own examples, and finally a look into the future detailing how these methods and technologies can be better implemented and thereby more time- and cost-effective and provide improved results.
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11.
  • Andreasson, Ulrika, et al. (författare)
  • B cell lymphomas express CX(3)CR1 a non-B cell lineage adhesion molecule
  • 2008
  • Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 259:2, s. 138-145
  • Tidskriftsartikel (refereegranskat)abstract
    • To study the differential expression of cell membrane-bound receptors and their potential role in growth and/or survival of the tumor cells, highly purified follicular lymphoma cells were analyzed, using gene expression analysis, and compared to non-malignant B cell populations. Filtering the genome for overexpressed genes coding for cell membrane-bound proteins/receptors resulted in a hit list of 27 identified genes. Among these, we have focused on the aberrant over expression of CX3CR1, in different types of B cell lymphoma, as compared to non-malignant B cells. We show that CX3CR1, which normally is not expressed on B cells, is expressed both at the mRNA and protein level in several subtypes of lymphoma. CX3CR1 has also shown to be involved in the homing to specific tissues that express the ligand, CX3CL1, in breast and prostate cancer and may thus be involved in dissemination of lymphoma.
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14.
  • Kreibich, Heidi, et al. (författare)
  • Adaptation to flood risk : Results of international paired flood event studies
  • 2017
  • Ingår i: Earth's Future. - 2328-4277. ; , s. 953-965
  • Tidskriftsartikel (refereegranskat)abstract
    • As flood impacts are increasing in large parts of the world, understanding the primary drivers of changes in risk is essential for effective adaptation. To gain more knowledge on the basis of empirical case studies, we analyze eight paired floods, that is, consecutive flood events that occurred in the same region, with the second flood causing significantly lower damage. These success stories of risk reduction were selected across different socioeconomic and hydro-climatic contexts. The potential of societies to adapt is uncovered by describing triggered societal changes, as well as formal measures and spontaneous processes that reduced flood risk. This novel approach has the potential to build the basis for an international data collection and analysis effort to better understand and attribute changes in risk due to hydrological extremes in the framework of the IAHSs Panta Rhei initiative. Across all case studies, we find that lower damage caused by the second event was mainly due to significant reductions in vulnerability, for example, via raised risk awareness, preparedness, and improvements of organizational emergency management. Thus, vulnerability reduction plays an essential role for successful adaptation. Our work shows that there is a high potential to adapt, but there remains the challenge to stimulate measures that reduce vulnerability and risk in periods in which extreme events do not occur.
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16.
  • Merz, K. E., et al. (författare)
  • Changes in Skeletal Muscle PAK1 Levels Regulate Tissue Crosstalk to Impact Whole Body Glucose Homeostasis
  • 2022
  • Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Skeletal muscle accounts for ~80% of insulin-stimulated glucose uptake. The Group I p21-activated kinase 1 (PAK1) is required for the non-canonical insulin-stimulated GLUT4 vesicle translocation in skeletal muscle cells. We found that the abundances of PAK1 protein and its downstream effector in muscle, ARPC1B, are significantly reduced in the skeletal muscle of humans with type 2 diabetes, compared to the non-diabetic controls, making skeletal muscle PAK1 a candidate regulator of glucose homeostasis. Although whole-body PAK1 knockout mice exhibit glucose intolerance and are insulin resistant, the contribution of skeletal muscle PAK1 in particular was unknown. As such, we developed inducible skeletal muscle-specific PAK1 knockout (skmPAK1-iKO) and overexpression (skmPAK1-iOE) mouse models to evaluate the role of PAK1 in skeletal muscle insulin sensitivity and glucose homeostasis. Using intraperitoneal glucose tolerance and insulin tolerance testing, we found that skeletal muscle PAK1 is required for maintaining whole body glucose homeostasis. Moreover, PAK1 enrichment in GLUT4-myc-L6 myoblasts preserves normal insulin-stimulated GLUT4 translocation under insulin resistance conditions. Unexpectedly, skmPAK1-iKO also showed aberrant plasma insulin levels following a glucose challenge. By applying conditioned media from PAK1-enriched myotubes or myoblasts to beta-cells in culture, we established that a muscle-derived circulating factor(s) could enhance beta-cell function. Taken together, these data suggest that PAK1 levels in the skeletal muscle can regulate not only skeletal muscle insulin sensitivity, but can also engage in tissue crosstalk with pancreatic beta-cells, unveiling a new molecular mechanism by which PAK1 regulates whole-body glucose homeostasis.
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17.
  • Muhlemann, B., et al. (författare)
  • Ancient hepatitis B viruses from the Bronze Age to the Medieval period
  • 2018
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 557:7705, s. 418-423
  • Tidskriftsartikel (refereegranskat)abstract
    • Hepatitis B virus (HBV) is a major cause of human hepatitis. There is considerable uncertainty about the timescale of its evolution and its association with humans. Here we present 12 full or partial ancient HBV genomes that are between approximately 0.8 and 4.5 thousand years old. The ancient sequences group either within or in a sister relationship with extant human or other ape HBV clades. Generally, the genome properties follow those of modern HBV. The root of the HBV tree is projected to between 8.6 and 20.9 thousand years ago, and we estimate a substitution rate of 8.04 x 10(-6-)1.51 x 10(-5) nucleotide substitutions per site per year. In several cases, the geographical locations of the ancient genotypes do not match present-day distributions. Genotypes that today are typical of Africa and Asia, and a subgenotype from India, are shown to have an early Eurasian presence. The geographical and temporal patterns that we observe in ancient and modern HBV genotypes are compatible with well-documented human migrations during the Bronze and Iron Ages(1,2). We provide evidence for the creation of HBV genotype A via recombination, and for a long-term association of modern HBV genotypes with humans, including the discovery of a human genotype that is now extinct. These data expose a complexity of HBV evolution that is not evident when considering modern sequences alone.
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18.
  • Pal, P., et al. (författare)
  • Resonant photoemission spectroscopy studies of the magnetic phase transitions in Pr(0.5)Sr(0.5)MnO(3)
  • 2011
  • Ingår i: Physica B: Condensed Matter. - : Elsevier BV. - 0921-4526 .- 1873-2135. ; 406:18, s. 3519-3523
  • Tidskriftsartikel (refereegranskat)abstract
    • The valence band electronic structure of Pr(0.5)Sr(0.5)MnO(3) has been investigated using resonant photoemission spectroscopies across its paramagnetic metallic (PMM)-ferromagnetic metallic (FMM)-antiferromagnetic insulator (AFMI) transition. Using bulk sensitive soft X-ray photoemission, we have confirmed the presence of a gap in the near Fermi level electronic spectrum in the charge ordering (CO) antiferromagnetic insulator (AFMI) phase. The Fermi level exhibits a rigid-band-like shift of about similar to 0.4 eV across the PMM to AFMI transition. Further, we have observed a similar shift of the Pr 4f states to higher binding energies when the sample goes to the CO-AFMI state. The spectral behavior indicates a strong charge carrier localization associated with a charge-density-wave gap related to the CO. On the other hand, the growth of spectral weight at the Fermi level in the PMM state could well be connected to the microscopic phase-separation model. (C) 2011 Elsevier B.V. All rights reserved.
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19.
  • Pal, Prabir, et al. (författare)
  • Resonant photoemission spectroscopy studies of the magnetic phase transitions in Pr0.5Sr0.5MnO3
  • 2011
  • Ingår i: Physica B: Condensed Matter. - : Elsevier BV. - 0921-4526. ; 406:18, s. 3519-3523
  • Tidskriftsartikel (refereegranskat)abstract
    • The valence band electronic structure of Pr0.5Sr0.5MnO3 has been investigated using resonant photoemission spectroscopies across its paramagnetic metallic (PMM)-ferromagnetic metallic (FMM)-antiferromagnetic insulator (AFMI) transition. Using bulk sensitive soft X-ray photoemission, we have confirmed the presence of a gap in the near Fermi level electronic spectrum in the charge ordering (CO) antiferromagnetic insulator (AFMI) phase. The Fermi level exhibits a rigid-band-like shift of about similar to 0.4 eV across the PMM to AFMI transition. Further, we have observed a similar shift of the Pr 4f states to higher binding energies when the sample goes to the CO-AFMI state. The spectral behavior indicates a strong charge carrier localization associated with a charge-density-wave gap related to the CO. On the other hand, the growth of spectral weight at the Fermi level in the PMM state could well be connected to the microscopic phase-separation model. (C) 2011 Elsevier B.V. All rights reserved.
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20.
  • Reynolds, Harmony R., et al. (författare)
  • Association of Sex With Severity of Coronary Artery Disease, Ischemia, and Symptom Burden in Patients With Moderate or Severe Ischemia Secondary Analysis of the ISCHEMIA Randomized Clinical Trial
  • 2020
  • Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:7, s. 773-786
  • Tidskriftsartikel (refereegranskat)abstract
    • Key PointsQuestion  When considering patients who have obstructive coronary artery disease and ischemia on stress testing, are there sex differences in severity of coronary artery disease, ischemia, and/or symptoms?Findings  In this secondary analysis of the ISCHEMIA randomized clinical trial of 5179 patients, women had more frequent angina, less extensive coronary artery disease, and less severe ischemia than men. On multivariate analysis, female sex was independently associated with greater angina frequency.Meaning  There may be inherent sex differences in the complex relationships between angina, ischemia, and atherosclerosis that may have implications for testing and treatment of patients with suspected coronary artery disease.AbstractImportance  While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization.Objective  To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants.Design, Setting, and Participants  This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018.Interventions  CCTA and angina assessment.Main Outcomes and Measures  Sex differences in stress test, CCTA findings, and symptom severity.Results  Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (353 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76).Conclusions and Relevance  Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease.
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21.
  • Reynolds, Harmony R., et al. (författare)
  • Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease : Insights From the ISCHEMIA Trial
  • 2024
  • Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:5
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWomen with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline‐directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management.Methods and ResultsThe ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline‐directed medical therapy, or initial conservative management with guideline‐directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive‐assigned women revascularized versus 81.2% of invasive‐assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive‐assigned women and 74.8% of invasive‐assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4‐year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline‐directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77–1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76–1.14]; P=0.49), with no significant sex‐by‐treatment‐group interactions.ConclusionsWomen had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk‐adjusted outcomes to men in the ISCHEMIA trial.
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22.
  • Sachpekidis, Christos, et al. (författare)
  • Artificial intelligence–based, volumetric assessment of the bone marrow metabolic activity in [ 18 F]FDG PET/CT predicts survival in multiple myeloma
  • 2024
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - 1619-7070 .- 1619-7089. ; 51:8, s. 2293-2307
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Multiple myeloma (MM) is a highly heterogeneous disease with wide variations in patient outcome. [18F]FDG PET/CT can provide prognostic information in MM, but it is hampered by issues regarding standardization of scan interpretation. Our group has recently demonstrated the feasibility of automated, volumetric assessment of bone marrow (BM) metabolic activity on PET/CT using a novel artificial intelligence (AI)–based tool. Accordingly, the aim of the current study is to investigate the prognostic role of whole-body calculations of BM metabolism in patients with newly diagnosed MM using this AI tool. Materials and methods: Forty-four, previously untreated MM patients underwent whole-body [18F]FDG PET/CT. Automated PET/CT image segmentation and volumetric quantification of BM metabolism were based on an initial CT-based segmentation of the skeleton, its transfer to the standardized uptake value (SUV) PET images, subsequent application of different SUV thresholds, and refinement of the resulting regions using postprocessing. In the present analysis, ten different uptake thresholds (AI approaches), based on reference organs or absolute SUV values, were applied for definition of pathological tracer uptake and subsequent calculation of the whole-body metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Correlation analysis was performed between the automated PET values and histopathological results of the BM as well as patients’ progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic (ROC) curve analysis was used to investigate the discrimination performance of MTV and TLG for prediction of 2-year PFS. The prognostic performance of the new Italian Myeloma criteria for PET Use (IMPeTUs) was also investigated. Results: Median follow-up [95% CI] of the patient cohort was 110 months [105–123 months]. AI-based BM segmentation and calculation of MTV and TLG were feasible in all patients. A significant, positive, moderate correlation was observed between the automated quantitative whole-body PET/CT parameters, MTV and TLG, and BM plasma cell infiltration for all ten [18F]FDG uptake thresholds. With regard to PFS, univariable analysis for both MTV and TLG predicted patient outcome reasonably well for all AI approaches. Adjusting for cytogenetic abnormalities and BM plasma cell infiltration rate, multivariable analysis also showed prognostic significance for high MTV, which defined pathological [18F]FDG uptake in the BM via the liver. In terms of OS, univariable and multivariable analysis showed that whole-body MTV, again mainly using liver uptake as reference, was significantly associated with shorter survival. In line with these findings, ROC curve analysis showed that MTV and TLG, assessed using liver-based cut-offs, could predict 2-year PFS rates. The application of IMPeTUs showed that the number of focal hypermetabolic BM lesions and extramedullary disease had an adverse effect on PFS. Conclusions: The AI-based, whole-body calculations of BM metabolism via the parameters MTV and TLG not only correlate with the degree of BM plasma cell infiltration, but also predict patient survival in MM. In particular, the parameter MTV, using the liver uptake as reference for BM segmentation, provides solid prognostic information for disease progression. In addition to highlighting the prognostic significance of automated, global volumetric estimation of metabolic tumor burden, these data open up new perspectives towards solving the complex problem of interpreting PET scans in MM with a simple, fast, and robust method that is not affected by operator-dependent interventions.
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23.
  • Smolentsev, Grigory, et al. (författare)
  • X-ray emission spectroscopy to study Ligand Valence Orbitals in Mn coordination complexes
  • 2009
  • Ingår i: Journal of the American Chemical Society. - : ACS Publications. - 0002-7863 .- 1520-5126. ; 131:36, s. 13161-13167
  • Tidskriftsartikel (refereegranskat)abstract
    • We discuss a spectroscopic method to determine the character of chemical bonding and for the identification of metal ligands in coordination and bioinorganic chemistry. It is based on the analysis of satellite lines in X-ray emission spectra that arise from transitions between valence orbitals and the metal ion 1s level (valence-to-core XES). The spectra, in connection with calculations based on density functional theory (DFT), provide information that is complementary to other spectroscopic techniques, in particular X-ray absorption (XANES and EXAFS). The spectral shape is sensitive to protonation of ligands and allows ligands, which differ only slightly in atomic number (e.g., C, N, O...), to be distinguished. A theoretical discussion of the main spectral features is presented in terms of molecular orbitals for a series of Mn model systems: [Mn(H2O)6]2+, [Mn(H2O)5OH]+, and [Mn(H2O)5NH3]2+. An application of the method, with comparison between theory and experiment, is presented for the solvated Mn2+ ion in water and three Mn coordination complexes, namely [LMn(acac)N3]BPh4, [LMn(B2O3Ph2)(ClO4)], and [LMn(acac)N]BPh4, where L represents 1,4,7-trimethyl-1,4,7-triazacyclononane, acac stands for the 2,4-pentanedionate anion, and B2O3Ph2 represents the 1,3-diphenyl-1,3-dibora-2-oxapropane-1,3-diolato dianion.
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