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August 03, 2018Article

White matter lesions

Spatial heterogeneity, links to risk factors, cognition, genetics, and atrophy

Mohamad Habes, Aristeidis Sotiras, Guray Erus, Jon B. Toledo, Deborah Janowitz, David A. Wolk, Haochang Shou, Nick R. Bryan, Jimit Doshi, Henry Völzke, Ulf Schminke, Wolfgang Hoffmann, Susan M. Resnick, Hans J. Grabe, Christos Davatzikos
First published August 3, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006116
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Article Information

10.1212/WNL.0000000000006116
DOI: 
https://doi.org/10.1212/WNL.0000000000006116
PubMed: 
30076276
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received July 28, 2017
  • Accepted in final form June 4, 2018
  • First Published August 3, 2018.

Article Versions

Copyright & Usage: 
© 2018 American Academy of Neurology

Author Disclosures

    1. Mohamad Habes, PhD,
    2. Aristeidis Sotiras, PhD,
    3. Guray Erus, PhD,
    4. Jon B. Toledo, MD,
    5. Deborah Janowitz, MD,
    6. David A. Wolk, MD,
    7. Haochang Shou, PhD,
    8. Nick R. Bryan, MD,
    9. Jimit Doshi, MSc,
    10. Henry Völzke, MD,
    11. Ulf Schminke, MD,
    12. Wolfgang Hoffmann, MD, MPH,
    13. Susan M. Resnick, PhD‡,
    14. Hans J. Grabe, MD‡ and
    15. Christos Davatzikos, PhD‡
  1. Mohamad Habes, PhD,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH (grant no. 1RF1AG054409)

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Dr. Mohamad Habes was supported in part by ?Alfried Krupp von Bohlen und Halbach? foundation. This work has been supported in part by The Allen H. and Selma W. Berkman Charitable Trust (Accelerating Research on Vascular Dementia)

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. Aristeidis Sotiras, PhD,
    3. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. (1) Method and device for efficient parallel message computation for maximum a posteriori inference

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. This work has been supported in part by NIH (grant no. 1RF1AG054409). Stock/Stock Options, Medical Equipment & Materials: (1) TheraPanacea (<1year)

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Guray Erus, PhD,
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. This work has been supported in part by NIH (grant no. 1RF1AG054409)

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. Jon B. Toledo, MD,
    5. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Eli-Lilly

    Research Support, Government Entities:

    1. NIH

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. Deborah Janowitz, MD,
    6. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. David A. Wolk, MD,
    7. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. 1. GE Healthcare, meeting registration

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Merck Eli Lilly Janssen

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. 1. Eli Lilly, Inc 2. AVID Radiopharmaceuticals 3. Merck 4. Biogen 5. Functional Neuromodulation

    Research Support, Government Entities:

    1. 1. NIH, AG040271, PI, 08/1/12-05/31/17 2. NIH, AG010124, Co-I, 09/30/90 - 06/30/16 3. NIH, EB016923, Co-I, 05/1/14 - 4/30/16 4. NIH, EB017255, Co-I, 08/01/2014 - 07/31/2019 5. NIH, AG047866, Co-I, 08/20/20015- 07/31/2019 6. NIH, AG024904, Site-PI, 09/30/2004 - 7/31/2016 7. NIH, AG055005, PI, 3/1/2017 - 2/28/2022 8. NIH, AG058065, MPI, 12/1/17 ? 11/30/22 9. NIH, AG054435, MPI, 04/01/17 ? 03/31/21 10. NIH, AG054409, MPI, 04/15/2017 ? 03/31/2022

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. 1. Michael J. Fox/Alzheimer?s Association 2. Alzheimer's Association

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  7. Haochang Shou, PhD,
    8. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. (1) Scientific reports, editorial member, 2015-present

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  8. Nick R. Bryan, MD,
    9. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH; PI Longitudinal Studies of Coronary Artery Risk Development in Young Adults; MRI Reading Center (CARDIA) 000501394-sc007, 2008-2017

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. GalileoCDS, Inc; founder, board member; stock equity; 2015 Stock/Stock Options, Medical Equipment & Materials: GalileoCDS, Inc; founder, board member; stock equity; 2015

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  9. Jimit Doshi, MSc,
    10. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  10. Henry Völzke, MD,
    11. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. BMBF

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  11. Ulf Schminke, MD,
    12. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. I received travel expenses and/or honoraria for lectures or educational activities not funded by industry and I received speaker?s honoraria from UCB Pharma GmbH, Germany.

    Editorial Boards:

    1. Member of the Editorial board of Cerebrovascular Diseases and Journal of Clinical Ultrasound

    Patents:

    1. NONE

    Publishing Royalties:

    1. I received royalties from the publication of the book Podrecznik diagnostyki ultrasonograficznej w neurologii from Czelej Publisher, Poland, in 2011, and from the book SOP's Neurophysiologische Diagnostik from Thieme Publisher, Germany, in 2018.

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. My research activities were funded Siemens Healthcare, Erlangen, Germany.

    Research Support, Government Entities:

    1. My research activities were funded by the National Institute of Neurological Disorders and Stroke (subaward #A08580 M10A10647), the Federal Ministry of Education and Research, Germany (grant #03IS2061A), the Federal State of Mecklenburg-West Pomerania, Germany.

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  12. Wolfgang Hoffmann, MD, MPH,
    13. Scientific Advisory Boards:

    1. (1) non-profit External Scientific Advisory Board of the centralized Interdisciplinary Bank of Biomaterials and Data W?rzburg (ibdw) (2) External scientific Advisory Board Hamburg City Health Study (HCHS)

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. commercial, monetary honorarium, speaker honorarium at Siemens Roadshow 2013, Roche Symposia on CRISP Lung Cancer Registry (total 4 times 2016-2018)

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. (1)Federal ministry of Social Affairs of Mecklenburg- Western Pomerania, Summative Evaluation Kif?g M-V, PI, 2012-2018; PI (2) Federal Ministry of Economy, Work and Health, Exemplary health care solutions for challenged regions in M-V (2016-2020)

    Research Support, Academic Entities:

    1. (1) BMBF (Ministry of Science), Feasibility- Studien/Pretest Nationale Kohorte: Zentrales Datenmanagement, PI, 2010-2013 (2)BMBF (Ministry of Science), Gesundheitsregion Ostseek?ste - HICARE; Projektfeld 4: "IT & Epidemiologie", PI, 2011-2014 (3) BMBF (Ministry of Science), GANI_MED Teilprojekt SB3: Medizininformatik (Kohortenmanagement und Forschungsplattform), PI, 2010-2014 (4)BMBF (Ministry of Science), Integrated Data Management and telemedical Monitoring (DZHK: PI.4 IT), PI, 2011-2015 (5) DFG, Wissenschaftliche Literaturversorgungs- und Informationssysteme (LIS) - Modulares Unterst?tzungssystem zur Planung und Implementierung eines zentralen Datenmanagements f?r Forschungsprojekte der Gesundheitsforschung, PI, 2012-2015

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  13. Susan M. Resnick, PhD‡,
    14. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Dr. Resnick has received travel reimbursement for her participation on the international advisory board for the Canadian Consortium on Neurodegeneration in Aging; Spouse has consulted and received travel reimbursement and honoraria from Dart Neuroscience and Roche and has received travel reimbursement and honoraria from University of California, Los Angeles

    Editorial Boards:

    1. Brain and Cognition (Action Editor)

    Patents:

    1. spouse has patent pending on Photoacoustic Voltage Sensitive Dyes for In Vivo Imaging

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. spouse - consultant Dart Neuroscience and Roche

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. spouse - grant and/or contract support unrelated to this study: Addex, Avid, Dart Neuroscience, Johnson and Johnson, Intracellular, Lundbeck, Pfizer, Roche, Takeda

    Research Support, Government Entities:

    1. NIA Intramural Research Program - Senior Investigator; spouse has NIH and CDC grants and contracts managed through Johns Hopkins University

    Research Support, Academic Entities:

    1. spouse - employed by Johns Hopkins University

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  14. Hans J. Grabe, MD‡ and
    15. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Fresenius Medical Care

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. Janssen

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Fresenius Medical Care

    Research Support, Government Entities:

    1. BMBF, DFG

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Damp

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  15. Christos Davatzikos, PhD‡
    16. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From the Center for Biomedical Image Computing and Analytics (M.H., A.S., G.E., N.R.B., J.D., C.D.), Department of Neurology and Penn Memory Center (M.H., D.A.W.), and Department of Biostatistics and Epidemiology (H.S.), University of Pennsylvania, Philadelphia; Department of Psychiatry (M.H., D.J., H.J.G.), Institute for Community Medicine (M.H., H.V., W.H.), and Department of Neurology (U.S.), University of Greifswald, Germany; Department of Neurology (J.B.T.), Houston Methodist Hospital, TX; German Center for Neurodegenerative Diseases (W.H., H.J.G.), Rostock/Greifswald, Germany; and Laboratory of Behavioral Neuroscience (S.M.R.), National Institute on Aging, Baltimore, MD.
  1. Correspondence
    Dr. Habes habesm{at}uphs.upenn.edu

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