Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation
Abstract
CNI-1493 is a potent anti-inflammatory agent, which deactivates macrophages and inhibits the synthesis of proinflammatory mediators. The objective of the present study was to identify the role of the central nervous system (CNS) and efferent vagus nerve signaling in CNI-1493-mediated modulation of acute inflammation in the periphery. CNI-1493 was administered either intracerebroventricularly (i.c.v., 0.1-1,000 ng/kg) or intravenously (i.v., 5 mg/kg) in anesthetized rats subjected to a standard model of acute inflammation (subcutaneous (s.c.) injection of carrageenan). I.c.v. CNI-1493 significantly suppressed carrageenan-induced paw edema, even in doses at least 6-logs lower than those required for a systemic effect. Bilateral cervical vagotomy or atropine blockade (1 mg/kg/h) abrogated the anti-inflammatory effects of CNI-1493 (1 microg/kg, i.c.v. or 5 mg/kg, i.v.), indicating that the intact vagus nerve is required for CNI-1493 activity. Recording of the efferent vagus nerve activity revealed an increase in discharge rate starting at 3-4 min after CNI-1493 administration (5 mg/kg, i.v.) and lasting for 10-14 min (control activity=87+/-5.4 impulses/s versus CNI-1493-induced activity= 229+/-6.7 impulses/s). Modulation of efferent vagus nerve activity by electrical stimulation (5 V, 2 ms, 1 Hz) of the transected peripheral vagus nerve for 20 min (10 min before carrageenan administration and 10 min after) also prevented the development of acute inflammation. Local administration of the vagus nerve neurotransmitter, acetylcholine (4 microg/kg, s.c.), or cholinergic agonists into the site of carrageenan-injection also inhibited acute inflammation. These results now identify a previously unrecognized role of efferent vagus nerve activity in mediating the central action of an anti-inflammatory agent.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Vagus nerve stimulation in carrageenan-induced paw swelling significantly attenuates edema formation and inhibits local production of cytokines in the zone of inflammation.
“Stimulation of the vagus nerve in animals subjected to carrageenan-induced paw swelling significantly attenuated the development of edema formation and inhibited the local production of cytokines in the zone of inflammation (23).”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [23]
Cites
Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
Borovikova, L. V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G. I., Watkins, L. R., Wang, H., Abumrad, N., Eaton, J. W., & Tracey, K. J. (2000) · Nature · doi:10.1038/35013070 · Cited by 4,211 · see citing works
Self-citationSecretory products of macrophages.
Nathan, C. F. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112815 · Cited by 2,615 · see citing works
Shock and Tissue Injury Induced by Recombinant Human Cachectin
Tracey, K. J., Beutler, B., Lowry, S. F., Merryweather, J., Wolpe, S., Milsark, I. W., Hariri, R. J., Fahey, T. J., Zentella, A., Albert, J. D., et al. (1986) · Science · doi:10.1126/science.3764421 · Cited by 2,549 · see citing works
Self-citationAuphan, N., DiDonato, J. A., Rosette, C., Helmberg, A., & Karin, M. (1995) · Science · doi:10.1126/science.270.5234.286 · Cited by 2,390 · see citing works
Immunoregulatory Feedback Between Interleukin-1 and Glucocorticoid Hormones
Besedovsky, H., del Rey, A., Sorkin, E., & Dinarello, C. A. (1986) · Science · doi:10.1126/science.3014662 · Cited by 1,519 · see citing works
Nitric oxide: a key mediator in the early and late phase of carrageenan‐induced rat paw inflammation
Salvemini, D., Wang, Z., Wyatt, P. S., Bourdon, D., Marino, M. H., Manning, P. T., & Currie, M. G. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb15475.x · Cited by 667 · see citing works
Cytokine-to-brain communication: A review & analysis of alternative mechanisms
Watkins, L. R., Maier, S. F., & Goehler, L. E. (1995) · Life Sciences · doi:10.1016/0024-3205(95)02047-m · Cited by 597 · see citing works
Watkins, L. R., Goehler, L. E., Relton, J. K., Tartaglia, N., Silbert, L., Martin, D., & Maier, S. F. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(94)11105-r · Cited by 516 · see citing works
The Role of the Vagus Nerve in Cytokine‐to‐Brain Communication
Maier, S. F., Goehler, L. E., Fleshner, M., & Watkins, L. R. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09569.x · Cited by 439 · see citing works
Pathway to carrageenan-induced inflammation in the hind limb of the rat.
Vinegar, R., Truax, J. F., Selph, J. L., et al. (1987) · PubMed · Cited by 328 · see citing works
Cytokines and Sickness Behavior
Dantzer, R., Bluthé, R.-M., Layé, S., Bret-Dibat, J. L., Parnet, P., & KELLEY, K. W. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09597.x · Cited by 303 · see citing works
Layé, S., Bluthé, R.-M., Kent, S., Combe, C., Medina, C. F., Parnet, P., Kelley, K., & Dantzer, R. (1995) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1995.268.5.r1327 · Cited by 303 · see citing works
Niijima, A. (1996) · Journal of the Autonomic Nervous System · doi:10.1016/s0165-1838(96)00098-7 · Cited by 261 · see citing works
Mechanisms of tumor necrosis factor-α (TNF-α) hyperalgesia
Watkins, L. R., Goehler, L. E., Relton, J. K., Brewer, M. T., & Maier, S. F. (1995) · Brain Research · doi:10.1016/0006-8993(95)00715-3 · Cited by 226 · see citing works
Bret-Dibat, J. L., Bluthé, R.-M., Kent, S., KELLEY, K. W., & Dantzer, R. (1995) · Brain Behavior and Immunity · doi:10.1006/brbi.1995.1023 · Cited by 224 · see citing works
The vagus nerve in the thermoregulatory response to systemic inflammation
Romanovsky, A. A., Simons, C. T., Székely, M., & KULCHITSKY, V. A. (1997) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1997.273.1.r407 · Cited by 196 · see citing works
Hansen, M. K., Taishi, P., Chen, Z., & Krueger, J. M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-06-02247.1998 · Cited by 193 · see citing works
TUMOR NECROSIS FACTOR IS A BRAIN DAMAGING CYTOKINE IN CEREBRAL ISCHEMIA
Meistrell, M., Botchkina, G., Wang, H., Santo, E. D., Cockroft, K., Bloom, O., Vishnubhakat, J., Ghezzi, P., & Tracey, K. (1997) · Shock · doi:10.1097/00024382-199711000-00005 · Cited by 192 · see citing works
Self-citationTumor necrosis factor is a brain damaging cytokine in cerebral ischemia.
Meistrell, M. E., Botchkina, G. I., Wang, H., Santo, E. D., Cockroft, K. M., Bloom, O., Vishnubhakat, J. M., Ghezzi, P., & Tracey, K. J. (1997) · PubMed · Cited by 168 · see citing works
Self-citationInterleukin-1 induces c-Fos immunoreactivity in primary afferent neurons of the vagus nerve
Goehler, L. E., Gaykema, R. P. A., Hammack, S. E., Maier, S. F., & Watkins, L. R. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00685-4 · Cited by 146 · see citing works
The Autonomic Nervous System as a Communication Channel between the Brain and the Immune System
Hori, T., Katafuchi, T., Take, S., Shimizu, N., & Niijima, A. (1996) · NeuroImmunoModulation · doi:10.1159/000097198 · Cited by 137 · see citing works
Suppression of proinflammatory cytokines in monocytes by a tetravalent guanylhydrazone.
Bianchi, M., Bloom, O., Raabe, T. D., Cohen, P. S., Chesney, J. A., Sherry, B. A., Schmidtmayerova, H., Calandra, T., Zhang, X., Bukrinsky, M., et al. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.3.927 · Cited by 127 · see citing works
Self-citationImmune regulation within the central nervous system
Xiao, B.-G., & Link, H. (1998) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(98)00049-5 · Cited by 126 · see citing works
Fleshner, M., Goehler, L. E., Schwartz, B. A., McGorry, M. M., Martin, D. A., Maier, S. F., & Watkins, L. R. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00026-5 · Cited by 124 · see citing works
Bacterial Endotoxin Induces Fos Immunoreactivity in Primary Afferent Neurons of the Vagus Nerve
Gaykema, R. P. A., Goehler, L. E., Tilders, F. J. H., Bol, J. G. J. M., McGorry, M. M., Fleshner, M., Maier, S. F., & Watkins, L. R. (1998) · NeuroImmunoModulation · doi:10.1159/000026343 · Cited by 118 · see citing works
Bianchi, M., Ulrich, P. C., Bloom, O., Meistrell, M. E., Zimmerman, G. A., Schmidtmayerova, H., Bukrinsky, M., Donnelley, T., Bucala, R., Sherry, B. A., et al. (1995) · Molecular Medicine · doi:10.1007/bf03401550 · Cited by 116 · see citing works
Self-citationThe Critical Role of p38 MAP Kinase in T Cell HIV-1 Replication
Cohen, P. S., Schmidtmayerova, H., Dennis, J., Dubrovsky, L., Sherry, B. A., Wang, H., Bukrinsky, M., & Tracey, K. J. (1997) · Molecular Medicine · doi:10.1007/bf03401812 · Cited by 107 · see citing works
Self-citationKAPCALA, L. P., CHAUTARD, T., & ESKAY, R. L. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb44699.x · Cited by 103 · see citing works
Antiinflammatory influences of alpha-MSH molecules: central neurogenic and peripheral actions
Macaluso, A., McCoy, D., Ceriani, G., Watanabe, T., BILTZ, J., Catania, A. P., & Jm, L. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-04-02377.1994 · Cited by 97 · see citing works
Cohen, P. S., Nakshatri, H., Dennis, J., Caragine, T. A., Bianchi, M., Cerami, A., & Tracey, K. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.3967 · Cited by 95 · see citing works
Self-citationSpermine inhibition of monocyte activation and inflammation
Zhang, M., Borovikova, L. V., Wang, H., Metz, C., & Tracey, K. J. (1999) · Molecular Medicine · doi:10.1007/bf03402072 · Cited by 92 · see citing works
Antiinflammatory Effects of the Neuropeptide α‐MSH in Acute, Chronic, and Systemic Inflammationa
Lipton, J. M., Ceriani, G., Macaluso, A., et al. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb39654.x · Cited by 84 · see citing works
Martiney, J., Rajan, A. J., Charles, P., Cerami, A., Ulrich, P., Macphail, S., Tracey, K., & Brosnan, C. (1998) · Journal of Immunology · doi:10.4049/jimmunol.160.11.5588 · Cited by 73 · see citing works
Self-citationVagal control of lymphocyte release from rat thymus
Antonica, A., Magni, F., Mearini, L., & Paolocci, N. (1994) · Journal of the Autonomic Nervous System · doi:10.1016/0165-1838(94)90047-7 · Cited by 72 · see citing works
Anti-tumor necrosis factor properties of non-peptide drugs in acute-phase responses
Chen, Y., Vraux, V. L., Giroud, J., et al. (1994) · European Journal of Pharmacology · doi:10.1016/0014-2999(94)90789-7 · Cited by 57 · see citing works
de Bock, F., Dérijard, B., Dornand, J., Bockaert, J., & Rondouin, G. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00317.x · Cited by 55 · see citing works
[28] Carrageenan foot edema test
Otterness, I. G., & Moore, P. F. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(88)62086-6 · Cited by 49 · see citing works
A Role for CRH and the Sympathetic Nervous System in Stress‐Induced Immunosuppressiona
Friedman, E. M., & Irwin, M. R. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb44698.x · Cited by 46 · see citing works
Marked antiinflammatory effects of decentralization of the superior cervical ganglia.
Ramaswamy, K., Mathison, R., Carter, L., et al. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.172.6.1819 · Cited by 42 · see citing works
Suppression of TNF and other proinflammatory cytokines by the tetravalent guanylhydrazone CNI-1493.
Tracey, K. J. (1998) · PubMed · Cited by 37 · see citing works
Self-citationPeptide Modulation of Inflammatory Processes within the Brain
Lipton, J. M., Catania, A. P., & Delgado, R. (1998) · NeuroImmunoModulation · doi:10.1159/000026335 · Cited by 32 · see citing works
Cholinergic signals to and from the immune system
Rinner, I., Felsner, P., Falus, A., et al. (1995) · Immunology Letters · doi:10.1016/0165-2478(94)00220-l · Cited by 30 · see citing works
Kemeny, M. M., Botchkina, G. I., Ochani, M., Bianchi, M., Urmacher, C., & Tracey, K. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.8.4561 · Cited by 19 · see citing works
Self-citationVilla, P., Meazza, C., Sironi, M., Bianchi, M., Ulrich, P. C., Botchkina, G. I., Tracey, K. J., & Ghezzi, P. (1997) · Journal of Endotoxin Research · doi:10.1177/096805199700400305 · Cited by 18 · see citing works
Self-citationVagus Nerve in Fever: Recent Developmentsa
Romanovsky, A. A., Simons, C. T., KULCHITSKY, V. A., et al. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb08343.x · Cited by 8 · see citing works
Borovikova, L. V., & Tracey, K. J. (1998) · Shock · doi:10.1097/00024382-199806001-00086 · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Tracey, K. J. (2002) · Nature · doi:10.1038/nature01321 · Cited by 3,728 · see citing works
Self-citationPhysiology and immunology of the cholinergic antiinflammatory pathway
Tracey, K. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30555 · Cited by 1,563 · see citing works
Self-citationThe vagus nerve at the interface of the microbiota-gut-brain axis
Bonaz, B., Bazin, T., & Pellissier, S. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00049 · Cited by 1,397 · see citing works
Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa
Dantzer, R. (2018) · Physiological Reviews · doi:10.1152/physrev.00039.2016 · Cited by 1,073 · see citing works
The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation
Pavlov, V. A., Wang, H., Czura, C. J., Friedman, S. G., & Tracey, K. J. (2003) · Molecular Medicine · doi:10.1007/bf03402177 · Cited by 772 · see citing works
Self-citationBonaz, B., Sinniger, V., & Pellissier, S. (2016) · The Journal of Physiology · doi:10.1113/jp271539 · Cited by 561 · see citing works
Pharmacological stimulation of the cholinergic antiinflammatory pathway
Bernik, T. R., Friedman, S. G., Ochani, M., DiRaimo, R., Ulloa, L., Yang, H., Sudan, S., Czura, C. J., Ivanova, S. M., & Tracey, K. J. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011714 · Cited by 529 · see citing works
Self-citationSaeed, R. W., Varma, S., Peng-Nemeroff, T., Sherry, B., Balakhaneh, D., Huston, J., Tracey, K. J., Al-Abed, Y., & Metz, C. N. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20040463 · Cited by 489 · see citing works
Self-citationThe role of inflammation and the gut microbiome in depression and anxiety
Peirce, J. M., & Alviña, K. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24476 · Cited by 466 · see citing works
Mikulska, J., Juszczyk, G., Gawrońska-Grzywacz, M., & Herbet, M. (2021) · Brain Sciences · doi:10.3390/brainsci11101298 · Cited by 450 · see citing works
Reflex principles of immunological homeostasis
Andersson, U., & Tracey, K. J. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075015 · Cited by 414 · see citing works
Self-citationRethinking inflammation: neural circuits in the regulation of immunity
Olofsson, P. S., Rosas‐Ballina, M., Levine, Y. A., & Tracey, K. J. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01138.x · Cited by 393 · see citing works
Self-citationGuarini, S., Altavilla, D., Cainazzo, M.-M., Giuliani, D., Bigiani, A., Marini, H., Squadrito, G., Minutoli, L., Bertolini, A., Marini, R., et al. (2003) · Circulation · doi:10.1161/01.cir.0000050627.90734.ed · Cited by 315 · see citing works
Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve
Luyer, M. D., Greve, J. W. M., Hadfoune, M., Jacobs, J. A., Dejong, C. H., & Buurman, W. A. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042397 · Cited by 295 · see citing works
The vagal innervation of the gut and immune homeostasis
Matteoli, G., & Boeckxstaens, G. E. (2013) · Gut · doi:10.1136/gutjnl-2012-302550 · Cited by 276 · see citing works
Autonomic neural regulation of immunity
CZURA, C. J., & TRACEY, K. J. (2005) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01442.x · Cited by 255 · see citing works
Self-citationCholinergic antiinflammatory pathway inhibition of tumor necrosis factor during ischemia reperfusion
Bernik, T. R., Friedman, S. G., Ochani, M., DiRaimo, R., Susarla, S., Czura, C. J., & Tracey, K. J. (2002) · Journal of Vascular Surgery · doi:10.1067/mva.2002.129643 · Cited by 228 · see citing works
Self-citationIdentification of a brainstem locus that inhibits tumor necrosis factor
Kressel, A. M., Tsaava, T., Levine, Y. A., Chang, E. H., Addorisio, M. E., Chang, Q., Burbach, B. J., Carnevale, D., Lembo, G., Zador, A. M., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2008213117 · Cited by 133 · see citing works
Self-citationDinan, T. G., Clarke, G., Quigley, E. M. M., Scott, L. V., Shanahan, F., Cryan, J., Cooney, J., & Keeling, P. W. N. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2008.01871.x · Cited by 136 · see citing works
GUARINI, S. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.03.029 · Cited by 131 · see citing works
The intestinal cholinergic anti-inflammatory pathway
Goverse, G., Stakenborg, M., & Matteoli, G. (2016) · The Journal of Physiology · doi:10.1113/jp271537 · Cited by 109 · see citing works
Altavilla, D., Guarini, S., Bitto, A., Mioni, C., Giuliani, D., Bigiani, A., Squadrito, G., Minutoli, L., Venuti, F. S., Messineo, F., et al. (2006) · Shock · doi:10.1097/01.shk.0000209539.91553.82 · Cited by 98 · see citing works
Kolacz, J., Kovacic, K. K., & Porges, S. W. (2019) · Developmental Psychobiology · doi:10.1002/dev.21852 · Cited by 94 · see citing works
Olofsson, P. S., Levine, Y. A., Caravaca, A., Chavan, S. S., Pavlov, V. A., Faltys, M., & Tracey, K. J. (2015) · Bioelectronic Medicine · doi:10.15424/bioelectronmed.2015.00006 · Cited by 81 · see citing works
Neural control of the immune system
Sundman, E., & Olofsson, P. S. (2014) · Advances in Physiology Education · doi:10.1152/advan.00094.2013 · Cited by 74 · see citing works
Hur, M. H., Song, W., Cheon, D.-H., Chang, Y., Cho, Y. Y., Lee, Y. B., Yu, S. J., Kim, Y. J., Yoon, J.-H., Choi, H. J., et al. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121533 · Cited by 17 · see citing works
- Authors
- Borovikova, L. V., Ivanova, S., Nardi, D., Zhang, M., Yang, H., Ombrellino, M., & Tracey, K. J.
- Affiliations
- North Shore University Hospital (US)
- Corresponding author
- Borovikova, Lyudmila V
- Venue
- Autonomic Neuroscience
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 85
- Issue
- 1-3
- Pages
- 141-147
- ISSN
- 1566-0702 (ISSN-L)
- OpenAlex
- W1973211651
- Cited by
- 322
- References
- 46
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 12 · 2023: 8 · 2022: 17 · 2021: 24 · 2020: 14 · 2019: 12 · 2018: 18 · 2017: 15 · 2016: 17 · 2015: 13 · 2014: 18 · 2013: 11 · 2012: 21
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Autonomic Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- CNI-1493, vagus nerve signaling, anti-inflammatory agents, acute inflammation, carrageenan-induced paw edema, vagotomy, atropine, acetylcholine, cholinergic agonists, macrophage deactivation, intracerebroventricular administration
- MeSH terms
- Acetylcholine, Acute Disease, Anilides, Animals, Atropine, Carrageenan, Dose-Response Relationship, Drug, Edema, Electric Stimulation, Ganglionic Stimulants, Guanidines, Hydrazones, Immunosuppressive Agents, Inflammation, Injections, Intraventricular, Male, Muscarine, Neurons, Efferent, Nicotine, Parasympathetic Nervous System, Parasympatholytics, Parasympathomimetics, Rats, Inbred Lew, Vagotomy, Vagus Nerve, Vasodilator Agents, Neuroimmunomodulation, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
