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Improved prediction and monitoring of central nervous system disorders with advanced neurophysiological and genetic assessment.

English title Improved prediction and monitoring of central nervous system disorders with advanced neurophysiological and genetic assessment.
Applicant Fuhr Peter
Number 140338
Funding scheme SPUM
Research institution Abteilung für Klinische Neurophysiologie Neurologische Universitätsklinik Kantonsspital Basel
Institution of higher education University of Basel - BS
Main discipline Neurology, Psychiatry
Start/End 01.04.2012 - 30.09.2016
Approved amount 1'800'000.00
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Keywords (8)

genetics; high-resolution EEG; surrogate marker; evoked potentials; neuropsychology; prognosis; connectivity; Multiple Sclerosis

Lay Summary (English)

Lead
Lay summary

Title: Improved prediction and monitoring of multiple sclerosis with advanced neurophysiological and genetic assessment (Prolongation of SPUM 33CM30-124115)

Objective: To develop quantitative measures and prognostic markers for the course of Multiple Sclerosis (MS), the most prevalent chronic brain disorder beginning in young adulthood.

Background: Due to imaging techniques, diagnosis of MS has greatly improved over the last two decades. However, a reliable prediction of the disease course (prognosis) is still not possible. Repetitive clinical examination is still the main tool to assess the course of disease and impairment. Objective and quantitative assessments resulting from neurophysiological measurements like electrical brain activity at rest (EEG) and during visual and sensory stimulation (evoked potentials, EP) represent parameters of impulse propagation in parts of the central nervous system. These measures are often abnormal early in the course of MS and yield important information on the prognosis. Recording them with high resolution (257 channels instead of 16 to 32), allowing much more precise identification and localization of pathological changes and analysis of network characteristics.

Methods: During the initial phase of the project a well-defined cohort has been prospectively recruited: 86 mildly impaired MS patients, in part with subtle cognitive deficits; they were matched to 53 normal controls. All subjects underwent clinical and neuropsychological assessments and had high-resolution EEG recordings; genetic data was collected from patients and will be collected from controls in the follow-up. During the prolongation period the observation period is extended by additional two years, which allows for important supplemental information on the prognostic value of the collected data.

EEG analyses include power spectra, topographical analysis of evoked potentials, characterization of connectivity with complex network analysis in signal and source space and microstate analysis. All analyses are performed in close collaboration of the participating centres in Switzerland (Basel, Geneva and Berne) and the research lab of Prof. C.J. Stam at VU Amsterdam. Finally, all results will be combined in a statistical model to monitor disease course and to predict clinical outcome.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
From swing to cane: Sex differences of EEG resting-state temporal patterns during maturation and aging
Tomescu M.I., Rihs T.A., Rochas V., Hardmeier M., Britz J., Allali G., Fuhr P., Eliez S., Michel C.M. (2018), From swing to cane: Sex differences of EEG resting-state temporal patterns during maturation and aging, in Developmental Cognitive Neuroscience, 31, 58-66.
A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS.
Hardmeier Martin, LeocaniLetizia, FuhrPeter (2017), A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS., in Multiple sclerosis (Houndmills, Basingstoke, England), 23(10), 1309-1319.
Clinical evoked potentials in neurology: a review of techniques and indications.
Lascano Agustina, Lalive Patrice, Hardmeier Martin, Fuhr Peter, Seeck Margitta (2017), Clinical evoked potentials in neurology: a review of techniques and indications., in Journal of neurology, neurosurgery, and psychiatry, 688-696.
Fluctuations of spontaneous EEG topographies predict disease state in relapsing-remitting multiple sclerosis
Gschwind Markus, Hardmeier Martin, Van De Ville Dimitri, Tomescu Miralena I., Penner Iris-Katharina, Naegelin Yvonne, Fuhr Peter, Michel Christoph M., Seeck Margitta (2016), Fluctuations of spontaneous EEG topographies predict disease state in relapsing-remitting multiple sclerosis, in NeuroImage: Clinical, 12, 466-477.
A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis.
Kuhle J, Hardmeier M, Disanto G, Gugleta K, Ecsedi M, Lienert C, Amato M P, Baum K, Buttmann M, Bayas A, Brassat D, Brochet B, Confavreux C, Edan G, Färkkilä M, Fredrikson S, Frontoni M, D'Hooghe M, Hutchinson M, De Keyser J, Kieseier B C, Kümpfel T, Rio J, Polman C, Roullet E (2016), A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis., in Multiple sclerosis (Houndmills, Basingstoke, England), 22(4), 533-43.
Microstate connectivity alterations in patients with early Alzheimer's disease.
Hatz Florian, Hardmeier Martin, Benz Nina, Ehrensperger Michael, Gschwandtner Ute, Rüegg Stephan, Schindler Chrisitan, Monsch Andreas U., Fuhr Peter (2016), Microstate connectivity alterations in patients with early Alzheimer's disease., in Alzheimer's Research & Therapy, 7, 78.
Monitoring multiple sclerosis by multimodal evoked potentials: Numerically versus ordinally scaled scoring systems.
Schlaeger Regina, Hardmeier Martin, D'Souza Marcus, Grize Leticia, Schindler Christian, Kappos Ludwig, Fuhr Peter (2016), Monitoring multiple sclerosis by multimodal evoked potentials: Numerically versus ordinally scaled scoring systems., in Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiol, 127(3), 1864-71.
Quantitative EEG and Cognitive Decline in Parkinson's Disease.
Cozac Vitalii V, Gschwandtner Ute, Hatz Florian, Hardmeier Martin, Rüegg Stephan, Fuhr Peter (2016), Quantitative EEG and Cognitive Decline in Parkinson's Disease., in Parkinson's Disease, 2016, 9060649.
Reliability of Functional Connectivity of Electroencephalography Applying Microstate-Segmented Versus Classical Calculation of Phase Lag Index.
Hatz Florian, Hardmeier Martin, Bousleiman Habib, Rüegg Stephan, Schindler Christian, Fuhr Peter (2016), Reliability of Functional Connectivity of Electroencephalography Applying Microstate-Segmented Versus Classical Calculation of Phase Lag Index., in Brain Connectivity, 6(6), 461-469.
Clinical Neurophysiology in multiple sclerosis - From diagnostic tool to biomarker
Fuhr Peter, Schindler Christian (2015), Clinical Neurophysiology in multiple sclerosis - From diagnostic tool to biomarker, in Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiolo, 126(1), 7-9.
Correlation of {EEG} Slowing with Cognitive Domains in Nondemented Patients with Parkinson's Disease
Zimmermann Ronan, Gschwandtner Ute, Hatz Florian, Schindler Christian, Bousleiman Habib, Ahmed Shaheen, Hardmeier Martin, Meyer Antonia, Calabrese Pasquale, Fuhr Peter (2015), Correlation of {EEG} Slowing with Cognitive Domains in Nondemented Patients with Parkinson's Disease, in Dementia and Geriatric Cognitive Disorders, 39(3-4), 207-214.
Correlation of EEG slowing with cognitive domains in nondemented patients with Parkinson's disease.
Zimmermann Ronan, Gschwandtner Ute, Hatz Florian, Schindler Christian, Bousleiman Habib, Ahmeed Shaheen, Hardmeier Martin, Meyer Antonia, Calabrese Pasquale, Fuhr Peter (2015), Correlation of EEG slowing with cognitive domains in nondemented patients with Parkinson's disease., in Dementia and Geriatric Cognitive Disorders, 39(3-4), 207-214.
Reliability of fully automated versus visually controlled pre- and post-processing of resting-state {EEG}
Hatz F., Hardmeier M., Bousleiman H., Rüegg S., Schindler C., Fuhr P. (2015), Reliability of fully automated versus visually controlled pre- and post-processing of resting-state {EEG}, in Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiolo, 126(2), 268-274.
Reliability of fully automated versus visually controlled pre- and post-processing of resting-state EEG.
Hatz Florian, Harmeier Martin, Bousleiman Habib, Rüegg Stephan, Schindler Christian, Fuhr Peter (2015), Reliability of fully automated versus visually controlled pre- and post-processing of resting-state EEG., in Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiolo, 126(2), 268-274.
Combined visual and motor evoked potentials predict multiple sclerosis disability after 20 years
Schlaeger Regina, Schindler Christian, Grize Leticia, Dellas Sophie, Radue Ernst W., Kappos Ludwig, Fuhr Peter (2014), Combined visual and motor evoked potentials predict multiple sclerosis disability after 20 years, in MULTIPLE SCLEROSIS JOURNAL, 20(10), 1348-1354.
Electrophysiological markers and predictors of the disease course in primary progressive multiple sclerosis
Schlaeger Regina, D'Souza Marcus, Schindler Christian, Grize Leticia, Kappos Ludwig, Fuhr Peter (2014), Electrophysiological markers and predictors of the disease course in primary progressive multiple sclerosis, in MULTIPLE SCLEROSIS JOURNAL, 20(1), 51-56.
Improved Characterization of Visual Evoked Potentials in Multiple Sclerosis by Topographic Analysis
Hardmeier Martin, Hatz Florian, Naegelin Yvonne, Hight Darren, Schindler Christian, Kappos Ludwig, Seeck Margitta, Michel Christoph M., Fuhr Peter (2014), Improved Characterization of Visual Evoked Potentials in Multiple Sclerosis by Topographic Analysis, in BRAIN TOPOGRAPHY, 27(2), 318-327.
Prediction of MS disability by multimodal evoked potentials: Investigation during relapse or in the relapse-free interval?
Schlaeger R., D'Souza M., Schindler C., Grize L., Kappos L., Fuhr P. (2014), Prediction of MS disability by multimodal evoked potentials: Investigation during relapse or in the relapse-free interval?, in CLINICAL NEUROPHYSIOLOGY, 125(9), 1889-1892.
Slowing of EEG background activity in Parkinson's and Alzheimer's disease with early cognitive dysfunction.
Benz Nina, Hatz Florian, Bousleiman Habib, Ehrensperger Michael M, Gschwandtner Ute, Hardmeier Martin, Ruegg Stephan, Schindler Christian, Zimmermann Ronan, Monsch Andreas Urs, Fuhr Peter (2014), Slowing of EEG background activity in Parkinson's and Alzheimer's disease with early cognitive dysfunction., in Frontiers in Aging Neuroscience, 6, 314.
Surgically Relevant Localization of the Central Sulcus With High-Density Somatosensory-Evoked Potentials Compared With Functional Magnetic Resonance Imaging
Lascano Agustina M., Grouiller Frederic, Genetti Melanie, Spinelli Laurent, Seeck Margitta, Schaller Karl, Michel Christoph M. (2014), Surgically Relevant Localization of the Central Sulcus With High-Density Somatosensory-Evoked Potentials Compared With Functional Magnetic Resonance Imaging, in NEUROSURGERY, 74(5), 517-526.
Combined visual and motor evoked potentials predict multiple sclerosis disability after 20 years
Schlaeger R., Schindler C., Grize L., Dellas S., Radue E. W., Kappos L., Fuhr P. (2013), Combined visual and motor evoked potentials predict multiple sclerosis disability after 20 years, in MULTIPLE SCLEROSIS JOURNAL, 19(11), 196-197.
Complex network analysis of high-resolution EEG data in multiple sclerosis patients with mild cognitive impairment and moderate fatigue
Hardmeier M., Hatz F., Penner I. K., Naegelin Y., Bousleiman H., Schindler C., Kappos L., Fuhr P. (2013), Complex network analysis of high-resolution EEG data in multiple sclerosis patients with mild cognitive impairment and moderate fatigue, in MULTIPLE SCLEROSIS JOURNAL, 19(11), 195-195.
Hippocampal sclerosis and chronic epilepsy following posterior reversible encephalopathy syndrome
Kapina Viktoria, Vargas Maria Isabel, Wohlrab Gabriele Christine, Vulliémoz Serge, Fluss Joël, Seeck Margitta (2013), Hippocampal sclerosis and chronic epilepsy following posterior reversible encephalopathy syndrome, in Epileptic Disorders, 15(4), 451-454.
Quantitative EEG and apolipoprotein E-genotype improve classification of patients with suspected Alzheimer's disease
Hatz F., Benz N., Hardmeier M., Zimmermann R., Rueegg S., Schindler C., Miserez A. R., Gschwandtner U., Monsch A. U., Fuhr P. (2013), Quantitative EEG and apolipoprotein E-genotype improve classification of patients with suspected Alzheimer's disease, in CLINICAL NEUROPHYSIOLOGY, 124(11), 2146-2152.
Cognitive dysfunction in early multiple sclerosis: altered centrality derived from resting-state functional connectivity using magneto-encephalography.
Hardmeier Martin, Schoonheim Menno M, Geurts Jeroen J G, Hillebrand Arjan, Polman Chris H, Barkhof Frederik, Stam Cornelis J (2012), Cognitive dysfunction in early multiple sclerosis: altered centrality derived from resting-state functional connectivity using magneto-encephalography., in PloS one, 7(7), 42087-42087.
Intranasal midazolam: pharmacokinetics and pharmacodynamics assessed by quantitative EEG in healthy volunteers.
Hardmeier M, Zimmermann R, Rüegg S, Pflüger M, Deuster S, Suter K, Donzelli M, Drewe J, Krähenbühl S, Fuhr P, Haschke M (2012), Intranasal midazolam: pharmacokinetics and pharmacodynamics assessed by quantitative EEG in healthy volunteers., in Clinical pharmacology and therapeutics, 91(5), 856-62.
Long term follow-up of executive functions after brain stimulation (DBS) in Parkinson's disease (PD) patients: Preliminary results
Schlede N., Gschwandtner U., Hatz F., Zimmermann R., Taub E., Ehrensperger M. M., Monsch A. U., Fuhr P. (2012), Long term follow-up of executive functions after brain stimulation (DBS) in Parkinson's disease (PD) patients: Preliminary results, in MOVEMENT DISORDERS, 27, 17-17.
Prediction of long-term disability in multiple sclerosis.
Schlaeger R, D'Souza M, Schindler C, Grize L, Dellas S, Radue E W, Kappos L, Fuhr P (2012), Prediction of long-term disability in multiple sclerosis., in Multiple sclerosis (Houndmills, Basingstoke, England), 18(1), 31-8.
Electrophysiological markers and predictors of the disease course in primary progressive multiple sclerosis.
Schlaeger Regina, D'Souza Marcus, Schindler Christian, Grize Leticia, Kappos Ludwig, Fuhr Peter, Electrophysiological markers and predictors of the disease course in primary progressive multiple sclerosis., in Multiple sclerosis (Houndmills, Basingstoke, England).
Power Spectra for Screening Parkinsonian Patients for Mild Cognitive Impairment
Bousleiman Habib, Zimmermann Ronan, Ahmed Shaheen, Hardmeier Martin, Hatz Florian, Schindler Christian, Roth Volker, Gschwandtner Ute, Fuhr Peter, Power Spectra for Screening Parkinsonian Patients for Mild Cognitive Impairment, in Annual of Clinical Translational Neurology.
Reproducibility of Functional Connectivity and Graph Measures Based on the Phase Lag Index (PLI) and Weighted Phase Lag Index (wPLI) Derived from High Resolution EEG
Hardmeier Martin, Hatz Florian, Bousleiman Habib, Schindler Christian, Stam Cornelis Jan, Fuhr Peter, Reproducibility of Functional Connectivity and Graph Measures Based on the Phase Lag Index (PLI) and Weighted Phase Lag Index (wPLI) Derived from High Resolution EEG, in PLOS ONE, 9(10).
Slowing of {EEG} background activity in Parkinson's and Alzheimer's disease with early cognitive dysfunction
Benz Nina, Hatz Florian, Bousleiman Habib, Ehrensperger Michael M., Gschwandtner Ute, Hardmeier Martin, Ruegg Stephan, Schindler Christian, Zimmermann Ronan, Monsch Andreas Urs, Fuhr Peter, Slowing of {EEG} background activity in Parkinson's and Alzheimer's disease with early cognitive dysfunction, in Frontiers in Aging Neuroscience, 6, 314-314.
Superficial brain stimulation. Research applications: Multiple Sclerosis
Schlaeger R Hardmeier M Fuhr P, Superficial brain stimulation. Research applications: Multiple Sclerosis, in Lozano A & Hallett M (ed.).

Collaboration

Group / person Country
Types of collaboration
Prof. V. Roth, Department of Mathematics and Computer Science, Universität Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Prof C.J. Stam, Dep. Clin. Neurophysiology, VUmc, Amsterdam Netherlands (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Prof. E.W. Radü, Universitätsspital Basel, MIAC, Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
XXI World Congress on Parkinson's Disease and Related Disorders Poster Brain network changes in relation to apathy and cognitive deficits in PD 06.12.2016 Milano, Italy Fuhr Peter; Hatz Florian;
XXI World Congress on Parkinson's Disease and Related Disorders Talk given at a conference Alpha reactivity (AR) of EEG as a marker for beginning of dementia in Parkinson’s disease (PD) patients with and without mild cognitive impairment (MCI) 06.12.2016 Milano, Italy Fuhr Peter; Hatz Florian;
XXI World Congress on Parkinson's Disease and Related Disorders Talk given at a conference Correlation of the EEG frequency with cognitive performance in Parkinson’s disease – six-months follow-up. 06.12.2016 Milano, Italy Fuhr Peter; Hatz Florian;
NMDPD 2016: Non-Motor Dysfunctions in Parkinson's Disease Talk given at a conference Influence of Age on Quantitative EEG Spectral Markers in Parkinson’s Disease (PD) 06.10.2016 Ljubljana, Slovenia Hatz Florian; Fuhr Peter;
NMDPD 2016: Non-Motor Dysfunctions in Parkinson's Disease Talk given at a conference Quantitative EEG and Verbal Fluency in Patients with Parkinson's Disease and STN-DBS 06.10.2016 Ljubljana, Slovenia Fuhr Peter; Hatz Florian;
NMDPD 2016: Non-Motor Dysfunctions in Parkinson's Disease Talk given at a conference Quantitative EEG (QEEG) in Parkinson Disease (PD) Patients with and without MCI – Application of the Least Absolute Shrinkage and Selection Operator (LASSO) 06.10.2016 Ljubljana, Slovenia Fuhr Peter; Hatz Florian;
NMDPD 2016: Non-Motor Dysfunctions in Parkinson's Disease Talk given at a conference EEG Connectivity in Parkinson’s Disease (PD) Patients with and without Mild Cognitive Impairment (MCI) 06.10.2015 Ljubljana, Slovenia Fuhr Peter; Hatz Florian;
Annual Meeting SSN 2015 Poster EEG topographical fluctuations predict disease state in minimally disabled multiple sclerosis patients 24.01.2015 Fribourg, Switzerland Seeck Margitta; Gschwind Markus; Fuhr Peter; Hardmeier Martin Ernst;
NMDPD Nice 2014 Talk given at a conference Quantitative EEG parameters as biomarker for Mild Cognitive Impairment in Parkinson's disease 04.12.2014 Nice, France Fuhr Peter;
NMDPD Nice 2014 Talk given at a conference Mild cognitive impairment and changes in brain network configuration in patients with Parkinson's disease 04.12.2014 Nice, France Hatz Florian; Fuhr Peter;
ICCN 2014 Poster Test-retest reliability and inter-subject variability of the Phase Lag Index (PLI), a measure of functional connectivity in EEG analysis 19.03.2014 Berlin, Germany Fuhr Peter; Schindler Christian; Hatz Florian; Hardmeier Martin Ernst;
ICCN 2014 Poster Increasing Reliability of EEG Frequency Analysis by Automated Rejection of EEG with Poor Quality 19.03.2014 Berlin, Germany Schindler Christian; Rüegg Stephan; Hatz Florian; Fuhr Peter; Hardmeier Martin Ernst;
ICCN 2014 Poster Full Automation versus Visual Control of the Pre- and Post-Processing of Resting-State EEG 19.03.2014 Berlin, Germany Rüegg Stephan; Hatz Florian; Fuhr Peter; Schindler Christian; Hardmeier Martin Ernst;
ECTRIMS Oct 2013 Poster Complex network analysis of high-resolution EEG data in MS patients with mild cognitive impairment and moderate fatigue 02.10.2013 Kopenhagen, Denmark Hatz Florian; Fuhr Peter; Schindler Christian; Penner Iris-Katharina; Kappos Ludwig; Hardmeier Martin Ernst;
ENS 2013 Poster Mild cognitive impairment (MCI) in Parkinson’s disease (PD-MCI) and in probable Alzheimer’s disease (ADMCI) with similar mini-mental state exams (MMSE) differ in quantitative EEG (QEEG) patterns 08.06.2013 Barcelona, Spain Hardmeier Martin Ernst; Rüegg Stephan; Hatz Florian; Monsch Andreas; Fuhr Peter;
2nd SFCNS Congress 2013 Poster Multichannel recordings of somatosensory evoked potentials in patients with multiple sclerosis: An objective analysis method 05.06.2013 Montreux, Switzerland Michel Christoph; Fuhr Peter; Hardmeier Martin Ernst; Kapina Viktoria; Seeck Margitta;
2nd SFCNS Congress 2013 Poster Coexistence of temporal lobe epilepsy and generalized epilepsy. A favorable outcome after surgery in 2 patients 05.06.2013 Montreux, Switzerland Seeck Margitta; Kapina Viktoria;
ICCN Berlin 2014 Talk given at a conference Utility of TMS in prediction of disability progression in Multiple Sclerosis 20.03.2013 Berlin, Germany Fuhr Peter;
ECTRIMS 2012 Talk given at a conference Topographic analysis of visual-evoked potentials improves sensitivity for previous optic neuritis 10.10.2012 Lyon, France Seeck Margitta; Michel Christoph; Schindler Christian; Hardmeier Martin Ernst; Hatz Florian; Fuhr Peter;


Knowledge transfer events



Self-organised

Title Date Place
Symposium of SNSF-Project 'Improved prediction and monitoring of central nervous system disorders with advanced neurophysiological and genetic assessment' 22.05.2015 Basel, Switzerland

Associated projects

Number Title Start Funding scheme
159682 Computer aided Methods for Diagnosis and Early Risk Assessment for Parkinson`s Disease Dementia 01.01.2016 Interdisciplinary projects
132952 The Idling Brain: The Temporal Structure of Resting State Networks Revealed by Electrical Neuroimaging 01.11.2010 Project funding (Div. I-III)
124115 Improved prediction and monitoring of CNS disorders with advanced neurophysiological and genetic assessment 01.04.2009 SPUM

Abstract

Objective: To develop quantitative surrogate measures and prognostic markers for the two most prevalent chronic brain disorders of adults, Multiple Sclerosis (MS) in the young and Alzheimer’s disease (AD) in the elderly, in a prospective longitudinal multicenter study.Methods: For this purpose, two well-defined cohorts have been prospectively recruited: 86 mildly impaired MS patients partly with subtle cognitive deficits, and 40 patients with amnesic mild cognitive impairment or early AD, both matched to normal controls. All subjects underwent thorough clinical and neuropsychological assessments and had high-resolution EEG recordings; genetic data were collected from patients only. EEG analyses include power spectra, topographical analysis of evoked potentials, characterization of connectivity with complex network analysis and microstate analysis.The best measures from these assessments will be combined in a final statistical model to monitor disease course and to predict clinical and cognitive outcome.The prolongation is requesteda) to complete the follow-up of the running project (MS Nov 2012, AD: Apr 13)b) to accomplish the cross-sectional and longitudinal analyses with advanced techniques, andc) to collect additional long-term data, as the probability of clinically relevant results increases with the duration of the observation period.
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