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Olfactory sniffing signals consciousness in unresponsive patients with brain injuries

Nature volume 581, pages 428–433 (2020)Cite this article

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Abstract

After severe brain injury, it can be difficult to determine the state of consciousness of a patient, to determine whether the patient is unresponsive or perhaps minimally conscious1, and to predict whether they will recover. These diagnoses and prognoses are crucial, as they determine therapeutic strategies such as pain management, and can underlie end-of-life decisions2,3. Nevertheless, there is an error rate of up to 40% in determining the state of consciousness in patients with brain injuries4,5. Olfaction relies on brain structures that are involved in the basic mechanisms of arousal6, and we therefore hypothesized that it may serve as a biomarker for consciousness7. Here we use a non-verbal non-task-dependent measure known as the sniff response8,9,10,11 to determine consciousness in patients with brain injuries. By measuring odorant-dependent sniffing, we gain a sensitive measure of olfactory function10,11,12,13,14,15. We measured the sniff response repeatedly over time in patients with severe brain injuries and found that sniff responses significantly discriminated between unresponsive and minimally conscious states at the group level. Notably, at the single-patient level, if an unresponsive patient had a sniff response, this assured future regaining of consciousness. In addition, olfactory sniff responses were associated with long-term survival rates. These results highlight the importance of olfaction in human brain function, and provide an accessible tool that signals consciousness and recovery in patients with brain injuries.

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Fig. 1: Measuring sniff responses in patients with DOC.
Fig. 2: The sniff response reflects the level of consciousness in patients with DOC.
Fig. 3: The sniff response is associated with the recovery of consciousness in patients with DOC.
Fig. 4: The sniff response is associated with long-term survival and functional recovery in patients with DOC.

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Data availability

Respiration data that support the findings of this study are available from GitLab (https://gitlab.com/liorg/OlfactorySniffingAnalysis/). Source data for Figs. 1–4 are provided with the paper.

Code availability

Custom code created and used in this study is available from GitLab (https://gitlab.com/liorg/OlfactorySniffingAnalysis/).

References

  1. Giacino, J. T. et al. Comprehensive systematic review update summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology 91, 461–470 (2018).

    PubMed  PubMed Central  Google Scholar 

  2. Giacino, J. T., Fins, J. J., Laureys, S. & Schiff, N. D. Disorders of consciousness after acquired brain injury: the state of the science. Nat. Rev. Neurol. 10, 99–114 (2014).

    PubMed  Google Scholar 

  3. Thibaut, A., Schiff, N., Giacino, J., Laureys, S. & Gosseries, O. Therapeutic interventions in patients with prolonged disorders of consciousness. Lancet Neurol. 18, 600–614 (2019).

    PubMed  Google Scholar 

  4. Stender, J. et al. Diagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study. Lancet 384, 514–522 (2014).

    PubMed  Google Scholar 

  5. Schnakers, C. et al. Diagnostic accuracy of the vegetative and minimally conscious state: clinical consensus versus standardized neurobehavioral assessment. BMC Neurol. 9, 35 (2009).

    PubMed  PubMed Central  Google Scholar 

  6. Price, J. L. in The Human Nervous System (ed. Paxinos, G) (Academic, 1990).

  7. Merrick, C., Godwin, C. A., Geisler, M. W. & Morsella, E. The olfactory system as the gateway to the neural correlates of consciousness. Front. Psychol. 4, 1011 (2014).

    PubMed  PubMed Central  Google Scholar 

  8. Mainland, J. & Sobel, N. The sniff is part of the olfactory percept. Chem. Senses 31, 181–196 (2006).

    PubMed  Google Scholar 

  9. Wachowiak, M. All in a sniff: olfaction as a model for active sensing. Neuron 71, 962–973 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Frank, R. A., Dulay, M. F. & Gesteland, R. C. Assessment of the sniff magnitude test as a clinical test of olfactory function. Physiol. Behav. 78, 195–204 (2003).

    CAS  PubMed  Google Scholar 

  11. Johnson, B. N., Mainland, J. D. & Sobel, N. Rapid olfactory processing implicates subcortical control of an olfactomotor system. J. Neurophysiol. 90, 1084–1094 (2003).

    PubMed  Google Scholar 

  12. Arzi, A. et al. Humans can learn new information during sleep. Nat. Neurosci. 15, 1460–1465 (2012).

    CAS  PubMed  Google Scholar 

  13. Rozenkrantz, L. et al. A mechanistic link between olfaction and autism spectrum disorder. Curr. Biol. 25, 1904–1910 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Arzi, A., Rozenkrantz, L., Holtzman, Y., Secundo, L. & Sobel, N. Sniffing patterns uncover implicit memory for undetected odors. Curr. Biol. 24, R263–R264 (2014).

    CAS  PubMed  Google Scholar 

  15. Reden, J., Draf, C., Frank, R. A. & Hummel, T. Comparison of clinical tests of olfactory function. Eur. Arch. Otorhinolaryngol. 273, 927–931 (2016).

    CAS  PubMed  Google Scholar 

  16. Rojas-Líbano, D. & Kay, L. M. Interplay between sniffing and odorant sorptive properties in the rat. J. Neurosci. 32, 15577–15589 (2012).

    PubMed  PubMed Central  Google Scholar 

  17. Johnson, B. N., Russell, C., Khan, R. M. & Sobel, N. A comparison of methods for sniff measurement concurrent with olfactory tasks in humans. Chem. Senses 31, 795–806 (2006).

    PubMed  Google Scholar 

  18. Arzi, A. et al. Olfactory aversive conditioning during sleep reduces cigarette-smoking behavior. J. Neurosci. 34, 15382–15393 (2014).

    PubMed  PubMed Central  Google Scholar 

  19. Giacino, J. T. & Kalmar, K. Coma Recovery Scale-Revised: Administration and Scoring Guidelines. https://www.tbims.org/combi/crs/CRS%20Syllabus.pdf (JFK Johnson Rehabilitation Institute and New Jersey Neuroscience Institute, JFK Medical Center, 2004).

  20. Rappaport, M., Dougherty, A. M. & Kelting, D. L. Evaluation of coma and vegetative states. Arch. Phys. Med. Rehabil. 73, 628–634 (1992).

    CAS  PubMed  Google Scholar 

  21. Bareham, C. A. et al. Longitudinal bedside assessments of brain networks in disorders of consciousness: case reports from the field. Front. Neurol. 9, 676 (2018).

    PubMed  PubMed Central  Google Scholar 

  22. Wannez, S., Heine, L., Thonnard, M., Gosseries, O. & Laureys, S. The repetition of behavioral assessments in diagnosis of disorders of consciousness. Ann. Neurol. 81, 883–889 (2017).

    PubMed  Google Scholar 

  23. Bareham, C. A. et al. Longitudinal assessments highlight long-term behavioural recovery in disorders of consciousness. Brain Commun. 1, fcz017 (2019).

    PubMed  PubMed Central  Google Scholar 

  24. Linacre, J. M., Heinemann, A. W., Wright, B. D., Granger, C. V. & Hamilton, B. B. The structure and stability of the functional independence measure. Arch. Phys. Med. Rehabil. 75, 127–132 (1994).

    CAS  PubMed  Google Scholar 

  25. Rowe, T. B., Macrini, T. E. & Luo, Z.-X. Fossil evidence on origin of the mammalian brain. Science 332, 955–957 (2011).

    ADS  CAS  PubMed  Google Scholar 

  26. Sela, L. & Sobel, N. Human olfaction: a constant state of change-blindness. Exp. Brain Res. 205, 13–29 (2010).

    PubMed  PubMed Central  Google Scholar 

  27. Keller, A. Attention and olfactory consciousness. Front. Psychol. 2, 380 (2011).

    PubMed  PubMed Central  Google Scholar 

  28. Stevenson, R. J. Phenomenal and access consciousness in olfaction. Conscious. Cogn. 18, 1004–1017 (2009).

    PubMed  Google Scholar 

  29. Nigri, A. et al. Central olfactory processing in patients with disorders of consciousness. Eur. J. Neurol. 23, 605–612 (2016).

    CAS  PubMed  Google Scholar 

  30. Arzi, A. et al. The influence of odorants on respiratory patterns in sleep. Chem. Senses 35, 31–40 (2010).

    PubMed  Google Scholar 

  31. Forgacs, P. B. et al. Preservation of electroencephalographic organization in patients with impaired consciousness and imaging-based evidence of command-following. Ann. Neurol. 76, 869–879 (2014).

    PubMed  PubMed Central  Google Scholar 

  32. Fernández-Espejo, D. et al. A role for the default mode network in the bases of disorders of consciousness. Ann. Neurol. 72, 335–343 (2012).

    PubMed  Google Scholar 

  33. Noirhomme, Q., Brecheisen, R., Lesenfants, D., Antonopoulos, G. & Laureys, S. “Look at my classifier’s result”: disentangling unresponsive from (minimally) conscious patients. Neuroimage 145, 288–303 (2017).

    PubMed  Google Scholar 

  34. Majdan, M. et al. Epidemiology of traumatic brain injuries in Europe: a cross-sectional analysis. Lancet Public Health 1, e76–e83 (2016).

    PubMed  Google Scholar 

  35. Aidinoff, E. et al. Vegetative state outcomes improved over the last two decades. Brain Inj. 32, 297–302 (2018).

    PubMed  Google Scholar 

  36. Monti, M. M. et al. Willful modulation of brain activity in disorders of consciousness. N. Engl. J. Med. 362, 579–589 (2010).

    ADS  CAS  PubMed  Google Scholar 

  37. Coleman, M. R. et al. Towards the routine use of brain imaging to aid the clinical diagnosis of disorders of consciousness. Brain 132, 2541–2552 (2009).

    CAS  PubMed  Google Scholar 

  38. Napolitani, M. et al. Transcranial magnetic stimulation combined with high-density EEG in altered states of consciousness. Brain Inj. 28, 1180–1189 (2014).

    PubMed  Google Scholar 

  39. Engemann, D. A. et al. Robust EEG-based cross-site and cross-protocol classification of states of consciousness. Brain 141, 3179–3192 (2018).

    PubMed  Google Scholar 

  40. Bekinschtein, T. A. et al. Classical conditioning in the vegetative and minimally conscious state. Nat. Neurosci. 12, 1343–1349 (2009).

    CAS  PubMed  Google Scholar 

  41. Green, P., Rohling, M. L., Iverson, G. L. & Gervais, R. O. Relationships between olfactory discrimination and head injury severity. Brain Inj. 17, 479–496 (2003).

    PubMed  Google Scholar 

  42. Sobel, N. et al. An impairment in sniffing contributes to the olfactory impairment in Parkinson’s disease. Proc. Natl Acad. Sci. USA 98, 4154–4159 (2001).

    ADS  CAS  PubMed  Google Scholar 

  43. Plotkin, A. et al. Sniffing enables communication and environmental control for the severely disabled. Proc. Natl Acad. Sci. USA 107, 14413–14418 (2010).

    ADS  CAS  PubMed  Google Scholar 

  44. Haviv, L. et al. Using a sniff controller to self-trigger abdominal functional electrical stimulation for assisted coughing following cervical spinal cord lesions. IEEE Trans. Neural Syst. Rehabil. Eng. 25, 1461–1471 (2017).

    PubMed  Google Scholar 

  45. Charland-Verville, V. et al. Detection of response to command using voluntary control of breathing in disorders of consciousness. Front. Hum. Neurosci. 8, 1020 (2014).

    PubMed  PubMed Central  Google Scholar 

  46. Owen, A. Into the Gray Zone: A Neuroscientist Explores the Border Between Life and Death (Simon and Schuster, 2017).

  47. Kondziella, D., Friberg, C. K., Frokjaer, V. G., Fabricius, M. & Møller, K. Preserved consciousness in vegetative and minimal conscious states: systematic review and meta-analysis. J. Neurol. Neurosurg. Psychiatry 87, 485–492 (2016).

    PubMed  Google Scholar 

  48. Borer-Alafi, N., Gil, M. Sazbon, L. & Korn, C. Loewenstein communication scale for the minimally responsive patient. Brain Inj. 16, 593–609 (2002).

    PubMed  Google Scholar 

  49. Seel, R. T. et al. Assessment scales for disorders of consciousness: evidence-based recommendations for clinical practice and research. Arch. Phys. Med. Rehabil. 91, 1795–1813 (2010).

    PubMed  Google Scholar 

  50. Rosenthal, R. in The Handbook of Research Synthesis (eds Cooper, H. & Hedges, L. V.) 231–244 (Russell Sage Foundation, 1994).

  51. Cliff, N. Dominance statistics: ordinal analyses to answer ordinal questions. Psychol. Bull. 114, 494–509 (1993).

    Google Scholar 

  52. Kim, H.-Y. Statistical notes for clinical researchers: chi-squared test and Fisher’s exact test. Restor. Dent. Endod. 42, 152–155 (2017).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the patients, their families and their caregivers for their cooperation; and O. Perl, L. Rösler and A. Elite for discussions. Work in the Sobel laboratory is supported by the Rob and Cheryl McEwen Fund for Brain Research. A.A. is supported by the Blavatnik Family Foundation, a Royal Society – Kohn International fellowship (NF150851) and an European Molecular Biology Organization (EMBO) fellowship (ALTF 33-2016).

Author information

Author notes

  1. These authors jointly supervised this work: Yaron Sacher, Noam Sobel

Authors and Affiliations

  1. Department of Psychology, University of Cambridge, Cambridge, UK

    Anat Arzi & Tristan A. Bekinschtein

  2. Azrieli Center for Human Brain Imaging and Research, Weizmann Institute of Science, Rehovot, Israel

    Anat Arzi, Liron Rozenkrantz, Lior Gorodisky, Yael Holtzman, Aharon Ravia & Noam Sobel

  3. Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel

    Anat Arzi, Liron Rozenkrantz, Lior Gorodisky, Yael Holtzman, Aharon Ravia & Noam Sobel

  4. Loewenstein Hospital Rehabilitation Center, Raanana, Israel

    Danit Rozenkrantz, Tatyana Galperin, Ben-Zion Krimchansky, Gal Cohen, Anna Oksamitni, Elena Aidinoff & Yaron Sacher

  5. Sackler Medical Faculty, Tel-Aviv University, Tel Aviv, Israel

    Yaron Sacher

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Contributions

Conceptualization: A.A. and N.S.; data collection: A.A., L.R. and L.G.; analysis: A.A., L.R., L.G., A.R. and N.S.; funding acquisition: A.A., N.S. and Y.S.; investigation: A.A., L.R., D.R. and Y.H.; methodology: A.A., L.R., L.G., A.R. and N.S.; project administration: A.A., L.R., D.R., Y.H., G.C., T.G., B.-Z.K., A.O., E.A., Y.S. and N.S.; resources: A.A., L.R., L.G., D.R., Y.H., G.C., T.G., B.-Z.K., A.O., E.A., Y.S. and N.S.; software: A.A., L.R. and L.G.; supervision: A.A., T.A.B., T.G., B.-Z.K., A.O., E.A., Y.S. and N.S.; validation: A.A., L.R. and L.G.; visualization: A.A. and N.S.; writing of the original draft: A.A. and N.S.; writing, review and editing: A.A., L.R., L.G., D.R., Y.H., T.A.B., G.C., T.G., B.-Z.K., A.O., E.A., Y.S. and N.S.

Corresponding authors

Correspondence to Anat Arzi or Noam Sobel.

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Competing interests

The findings of this manuscript are being used by the Weizmann Institute Office of Technology Licensing (Yeda) for the submission of a patent for a method of the detection of consciousness.

Additional information

Peer review information Nature thanks Hakwan Lau, Johan Lundström, Nicholas Schiff and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data figures and tables

Extended Data Fig. 1 The sniff response reflects the current level of consciousness in patients with DOC.

Data are displayed by odorant and sniff. a–i, Normalized sniff volume after pleasant odorants (a, d, g), unpleasant odorants (b, e, h) and blank (c, f, i) during UWS (U) sessions (outline; n = 73) and MCS (M) sessions (filled; n = 73) for the first (a–c), second (d–f) and third (g–i) sniff after stimulus delivery. Left, each dot represents a session; flat violin plots show the distribution; the red lines denote the median; and the dashed horizontal lines denote the baseline value at 1 NFU. Right, data are the mean ± s.e.m. for each distribution. The P values beneath the distribution denotes its difference from baseline inhalation. The P values above the distributions denote the difference in sniff response across groups. P values were calculated using two-tailed Wilcoxon signed-rank tests for within-group comparisons and Wilcoxon rank-sum tests for between-group comparisons corrected for multiple comparisons. Corrected P values are indicated by an asterisk (*) and uncorrected P values are indicated by a hash (#) symbol (see Methods). *P < 0.05; #P < 0.05. Further analyses are provided in the Supplementary Information.

Extended Data Fig. 2 The sniff response to pure olfactory odorants in patients with DOC.

To estimate whether the effects that we observed were dependent on the contribution of the trigeminal nerve, we exposed a subset of patients to pure olfactory odorants and observed the replication of the effects. The normalized sniff volume after exposure to the pure olfactants of the pleasant odorant (phenylethyl alcohol; a, c, e) and unpleasant odorant (decanoic acid; b, d, f) during UWS sessions (outline; pleasant, n = 56; unpleasant, n = 57) and MCS sessions (filled; pleasant, n = 56; unpleasant n = 56) for the first (a, b), second (c, d) and third (e, f) sniff after odorant delivery. Left, each dot represents a session; flat violin plots show the distribution; the red lines denote the median; and the dashed horizontal lines denote the baseline value at 1 NFU. Right, data are the mean ± s.e.m. for each distribution. The P value beneath the distribution denotes its difference from baseline inhalation—that is, the existence of a sniff response. *P < 0.05; two-tailed Wilcoxon test. Further analyses are provided in the Supplementary Information.

Extended Data Fig. 3 The sniff response is similar with and without tracheostomy.

Normalized sniff volume after pleasant (a, c, e) or unpleasant (b, d, f) odorants during MCS sessions with (W; n = 44) and without (O; n = 29) tracheostomy for the first (a, b), second (c, d) and third (e, f) sniff after odorant delivery. Left, each dot represents a session; flat violin plots show the distribution; the red lines denote the median; and the dashed horizontal lines denote the baseline value at 1 NFU. Right, data are the mean ± s.e.m. for each distribution. The P value beneath the distribution denotes its difference from baseline inhalation—that is, the existence of a sniff response. *P < 0.05; two-tailed Wilcoxon test. About 60% of MCS sessions and 80% of UWS sessions were conducted in patients with a tracheostomy. Although tracheostomy significantly reduces nasal airflow, a measurable portion of nasal airflow remains. For example, we note that the raw data in Fig. 1c, d were obtained with a tracheostomy. Further analyses are provided in the Supplementary Information.

Extended Data Fig. 4 The sniff response during MCS sessions.

The red lines denote the sniff-response threshold (more than 15% change in magnitude and/or 0.35 s.d.): dots within the lines (white background) reflect sessions without a sniff response; dots beyond the lines (shaded background) reflect sessions with a sniff response. a–c, Each dot is a MCS session. a, Pleasant odorant. b, Unpleasant odorant. c, Blank. d, Percentage of patients in a MCS (not sessions) with sniff responses (white, 64.5%) and without sniff responses (red, 35.5%) across all three conditions.

Extended Data Fig. 5 The sniff response is prognostic for the recovery of consciousness and long-term survival in patients with DOC.

Data are shown by patient rather than by session. The red lines denote the threshold of a sniff response (more than 15% change in magnitude and/or 0.35 s.d.). a–c, Each dot is a session with the strongest sniff response of a patient in a MCS (n = 19). a, Pleasant odorant. b, Unpleasant odorant. c, Blank. d, Percentage of patients in a MCS with sniff responses (white, 64.5%) and without sniff responses (red, 35.5%) across all three conditions. e–g, Each dot is a session with the strongest sniff response of a patient with UWS; empty dots represent patients who later recovered (transitioned to MCS; n = 16) and filled dots represent patients who did not recover and remain unconscious (n = 8). e, Pleasant odorant. f, Unpleasant odorant. g, Blank. h, Percentage of patients with UWS who later transitioned to MCS (left, recovered) and who remain unconscious (right, unrecovered) with sniff responses (white; recovered, 62.5%; unrecovered, 0%) and without sniff responses (red; recovered, 37.5%; unrecovered, 100%) across all three conditions. i–k, Each dot is a patient with DOC (MCS and UWS; n = 43); filled black dots represent patients who died during the study and coloured dots represent patients who survived during the study (mean ± s.d., 37.3 ± 14.1 months after brain injury). i, Pleasant odorant. j, Unpleasant odorant. k, Blank. l, Percentage of patients with DOC with sniff responses (left) who survived (white, 91.7%) and who are deceased (D) (red, 8.3%) and of patients with DOC without sniff responses who survived (white, 36.8%) and are deceased (red, 63.2%). m–o, Relation between the functional independence measure and normalized sniff volume. Each dot is a patient with UWS who survived during the study (n = 12). m, Pleasant odorant. n, Unpleasant odorant. o, Blank. r represents Spearman correlation.

Extended Data Fig. 6 Dependence of the predictive value on sniff-response thresholds in patients with UWS.

a, The receiver-operating characteristic (ROC) for a range of sniff-response volume thresholds for a sniff-response volume variability threshold of 0.35. b, The ROC for a range of sniff-response volume variability thresholds for a sniff-response volume threshold of 0.85 (15% reduction). c, Distance from a randomized predictor for a range of sniff-response volume thresholds for a sniff-response volume variability threshold of 0.35. d, Distance from randomized predictor for a range of sniff-response volume variability thresholds for a sniff-response volume threshold of 0.85. e, Area under the curve (AuC) for different sniff-response volume variability thresholds. f, Area under the curve for different sniff-response volume thresholds. n = 24. Further analyses are provided in the Supplementary Information.

Extended Data Fig. 7 Dependence of the sensitivity and specificity on sniff-response thresholds.

a, Sensitivity (true-positive rate (TPR)) for a range of sniff-response volume and sniff-response volume variability thresholds. b, Specificity (true-negative rate (TNR)) for a range of sniff-response volume and sniff-response volume variability thresholds. c, Distance from a randomized predictor for a range of sniff-response volume and sniff-response volume variability thresholds. Further analyses are provided in the Supplementary Information.

Extended Data Fig. 8 Dependence of the predictive value on the relation between conditions.

a, ROC for a range of differences in the sniff-response volume between the unpleasant odorant and the blank. b, The true-positive and true-negative rates for a range of differences in the sniff-response volume between the unpleasant odorant and the blank. c, ROC for a range of differences in the sniff-response volume between the pleasant odorant and the blank. d, The true-positive and true-negative rates for a range of differences in the sniff-response volume between the pleasant odorant and the blank. e, ROC for a range of differences in the sniff-response volume between the pleasant and unpleasant odorants. f, The true-positive and true-negative rates for a range of differences in the sniff-response volume between the pleasant and unpleasant odorants. n = 24. Further analyses are provided in the Supplementary Information.

Extended Data Table 1 Patient information
Full size table
Extended Data Table 2 Damage to olfactory-related brain areas
Full size table

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Supplementary Information

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Arzi, A., Rozenkrantz, L., Gorodisky, L. et al. Olfactory sniffing signals consciousness in unresponsive patients with brain injuries. Nature 581, 428–433 (2020). https://doi.org/10.1038/s41586-020-2245-5

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