{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:10:59Z","timestamp":1790946659582,"version":"4.1.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T00:00:00Z","timestamp":1505692800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Neurosci"],"published-print":{"date-parts":[[2017,11]]},"DOI":"10.1038\/nn.4643","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T11:08:50Z","timestamp":1505732930000},"page":"1549-1559","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":179,"title":["Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex"],"prefix":"10.1038","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8283-7976","authenticated-orcid":false,"given":"Harald","family":"Pr\u00fcss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Tedeschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude","family":"Thiriot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M","family":"Loughhead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0277-6403","authenticated-orcid":false,"given":"Susanne","family":"Stutte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina B","family":"Mazo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6832-9599","authenticated-orcid":false,"given":"Marcel A","family":"Kopp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3362-9780","authenticated-orcid":false,"given":"Benedikt","family":"Brommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Blex","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura-Christin","family":"Geurtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6025-6564","authenticated-orcid":false,"given":"Thomas","family":"Liebscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Niedeggen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0755-6119","authenticated-orcid":false,"given":"Ulrich","family":"Dirnagl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Bradke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena S","family":"Volz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"DeVivo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4231-2283","authenticated-orcid":false,"given":"Ulrich H","family":"von Andrian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6784-4919","authenticated-orcid":false,"given":"Jan M","family":"Schwab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,18]]},"reference":[{"key":"BFnn4643_CR1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/ni1078","volume":"5","author":"L Steinman","year":"2004","unstructured":"Steinman, L. Elaborate interactions between the immune and nervous systems. Nat. Immunol. 5, 575\u2013581 (2004).","journal-title":"Nat. Immunol."},{"key":"BFnn4643_CR2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nri3042","volume":"11","author":"MR Irwin","year":"2011","unstructured":"Irwin, M.R. & Cole, S.W. Reciprocal regulation of the neural and innate immune systems. Nat. Rev. Immunol. 11, 625\u2013632 (2011).","journal-title":"Nat. Rev. Immunol."},{"key":"BFnn4643_CR3","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/nrn1765","volume":"6","author":"C Meisel","year":"2005","unstructured":"Meisel, C., Schwab, J.M., Prass, K., Meisel, A. & Dirnagl, U. Central nervous system injury-induced immune deficiency syndrome. Nat. Rev. Neurosci. 6, 775\u2013786 (2005).","journal-title":"Nat. Rev. Neurosci."},{"key":"BFnn4643_CR4","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1111\/j.1471-4159.2009.06232.x","volume":"110","author":"KM Lucin","year":"2009","unstructured":"Lucin, K.M., Sanders, V.M. & Popovich, P.G. Stress hormones collaborate to induce lymphocyte apoptosis after high level spinal cord injury. J. Neurochem. 110, 1409\u20131421 (2009).","journal-title":"J. Neurochem."},{"key":"BFnn4643_CR5","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1111\/j.1460-9568.2007.05447.x","volume":"25","author":"T Riegger","year":"2007","unstructured":"Riegger, T. et al. Spinal cord injury-induced immune depression syndrome (SCI-IDS). Eur. J. Neurosci. 25, 1743\u20131747 (2007).","journal-title":"Eur. J. Neurosci."},{"key":"BFnn4643_CR6","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.4049\/jimmunol.1101934","volume":"188","author":"MA Oropallo","year":"2012","unstructured":"Oropallo, M.A. et al. Chronic spinal cord injury impairs primary antibody responses but spares existing humoral immunity in mice. J. Immunol. 188, 5257\u20135266 (2012).","journal-title":"J. Immunol."},{"key":"BFnn4643_CR7","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.neuroscience.2008.08.021","volume":"158","author":"T Riegger","year":"2009","unstructured":"Riegger, T. et al. Immune depression syndrome following human spinal cord injury (SCI): a pilot study. Neuroscience 158, 1194\u20131199 (2009).","journal-title":"Neuroscience"},{"key":"BFnn4643_CR8","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1097\/01.brs.0000244569.91204.01","volume":"31","author":"JC Furlan","year":"2006","unstructured":"Furlan, J.C., Krassioukov, A.V. & Fehlings, M.G. Hematologic abnormalities within the first week after acute isolated traumatic cervical spinal cord injury: a case-control cohort study. Spine 31, 2674\u20132683 (2006).","journal-title":"Spine"},{"key":"BFnn4643_CR9","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1093\/brain\/awv375","volume":"139","author":"B Brommer","year":"2016","unstructured":"Brommer, B. et al. Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level. Brain 139, 692\u2013707 (2016).","journal-title":"Brain"},{"key":"BFnn4643_CR10","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1001\/archinte.1989.00390080043011","volume":"149","author":"MJ DeVivo","year":"1989","unstructured":"DeVivo, M.J., Kartus, P.L., Stover, S.L., Rutt, R.D. & Fine, P.R. Cause of death for patients with spinal cord injuries. Arch. Intern. Med. 149, 1761\u20131766 (1989).","journal-title":"Arch. Intern. Med."},{"key":"BFnn4643_CR11","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/0003-9993(94)90027-2","volume":"75","author":"AB Jackson","year":"1994","unstructured":"Jackson, A.B. & Groomes, T.E. Incidence of respiratory complications following spinal cord injury. Arch. Phys. Med. Rehabil. 75, 270\u2013275 (1994).","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"BFnn4643_CR12","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1093\/brain\/aws267","volume":"135","author":"V Failli","year":"2012","unstructured":"Failli, V. et al. Functional neurological recovery after spinal cord injury is impaired in patients with infections. Brain 135, 3238\u20133250 (2012).","journal-title":"Brain"},{"key":"BFnn4643_CR13","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1212\/WNL.0000000000003652","volume":"88","author":"MA Kopp","year":"2017","unstructured":"Kopp, M.A. et al. Long-term functional outcome in patients with acquired infections after acute spinal cord injury. Neurology 88, 892\u2013900 (2017).","journal-title":"Neurology"},{"key":"BFnn4643_CR14","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/35013070","volume":"405","author":"LV Borovikova","year":"2000","unstructured":"Borovikova, L.V. et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458\u2013462 (2000).","journal-title":"Nature"},{"key":"BFnn4643_CR15","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1113\/jphysiol.2013.268573","volume":"592","author":"D Martelli","year":"2014","unstructured":"Martelli, D., Yao, S.T., McKinley, M.J. & McAllen, R.M. Reflex control of inflammation by sympathetic nerves, not the vagus. J. Physiol. (Lond.) 592, 1677\u20131686 (2014).","journal-title":"J. Physiol. (Lond.)"},{"key":"BFnn4643_CR16","doi-asserted-by":"crossref","first-page":"12970","DOI":"10.1523\/JNEUROSCI.1974-13.2013","volume":"33","author":"Y Zhang","year":"2013","unstructured":"Zhang, Y. et al. Autonomic dysreflexia causes chronic immune suppression after spinal cord injury. J. Neurosci. 33, 12970\u201312981 (2013).","journal-title":"J. Neurosci."},{"key":"BFnn4643_CR17","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/nn.4289","volume":"19","author":"M Ueno","year":"2016","unstructured":"Ueno, M., Ueno-Nakamura, Y., Niehaus, J., Popovich, P.G. & Yoshida, Y. Silencing spinal interneurons inhibits immune suppressive autonomic reflexes caused by spinal cord injury. Nat. Neurosci. 19, 784\u2013787 (2016).","journal-title":"Nat. Neurosci."},{"key":"BFnn4643_CR18","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1002\/ana.20105","volume":"55","author":"KJ Meador","year":"2004","unstructured":"Meador, K.J. et al. Role of cerebral lateralization in control of immune processes in humans. Ann. Neurol. 55, 840\u2013844 (2004).","journal-title":"Ann. Neurol."},{"key":"BFnn4643_CR19","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1468-1331.2012.03818.x","volume":"20","author":"U Walter","year":"2013","unstructured":"Walter, U. et al. Insular stroke is associated with acute sympathetic hyperactivation and immunodepression. Eur. J. Neurol. 20, 153\u2013159 (2013).","journal-title":"Eur. J. Neurol."},{"key":"BFnn4643_CR20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0361-9230(81)80072-X","volume":"6","author":"JM Williams","year":"1981","unstructured":"Williams, J.M. et al. Sympathetic innervation of murine thymus and spleen: evidence for a functional link between the nervous and immune systems. Brain Res. Bull. 6, 83\u201394 (1981).","journal-title":"Brain Res. Bull."},{"key":"BFnn4643_CR21","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/jnr.490180107","volume":"18","author":"DL Felten","year":"1987","unstructured":"Felten, D.L., Ackerman, K.D., Wiegand, S.J. & Felten, S.Y. Noradrenergic sympathetic innervation of the spleen: I. Nerve fibers associate with lymphocytes and macrophages in specific compartments of the splenic white pulp. J. Neurosci. Res. 18, 28\u201336, 118\u2013121 (1987).","journal-title":"J. Neurosci. Res."},{"key":"BFnn4643_CR22","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/sc.2008.87","volume":"47","author":"JG Previnaire","year":"2009","unstructured":"Previnaire, J.G., Soler, J.M., El Masri, W. & Denys, P. Assessment of the sympathetic level of lesion in patients with spinal cord injury. Spinal Cord 47, 122\u2013127 (2009).","journal-title":"Spinal Cord"},{"key":"BFnn4643_CR23","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1126\/science.1210301","volume":"334","author":"CH Wong","year":"2011","unstructured":"Wong, C.H., Jenne, C.N., Lee, W.Y., L\u00e9ger, C. & Kubes, P. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science 334, 101\u2013105 (2011).","journal-title":"Science"},{"key":"BFnn4643_CR24","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.cell.2007.09.047","volume":"131","author":"S Massberg","year":"2007","unstructured":"Massberg, S. et al. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell 131, 994\u20131008 (2007).","journal-title":"Cell"},{"key":"BFnn4643_CR25","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0165-1838(80)90043-0","volume":"2","author":"K Dembowsky","year":"1980","unstructured":"Dembowsky, K., Czachurski, J., Amendt, K. & Seller, H. Tonic descending inhibition of the spinal somato-sympathetic reflex from the lower brain stem. J. Auton. Nerv. Syst. 2, 157\u2013182 (1980).","journal-title":"J. Auton. Nerv. Syst."},{"key":"BFnn4643_CR26","doi-asserted-by":"crossref","first-page":"633","DOI":"10.3171\/jns.1979.50.5.0633","volume":"50","author":"PA Tibbs","year":"1979","unstructured":"Tibbs, P.A., Young, B., McAllister, R.G. Jr. & Todd, E.P. Studies of experimental cervical spinal cord transection. Part III: Effects of acute cervical spinal cord transection on cerebral blood flow. J. Neurosurg. 50, 633\u2013638 (1979).","journal-title":"J. Neurosurg."},{"key":"BFnn4643_CR27","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3171\/jns.1979.50.1.0058","volume":"50","author":"SE Rawe","year":"1979","unstructured":"Rawe, S.E. & Perot, P.L. Jr. Pressor response resulting from experimental contusion injury to the spinal cord. J. Neurosurg. 50, 58\u201363 (1979).","journal-title":"J. Neurosurg."},{"key":"BFnn4643_CR28","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3171\/jns.1980.52.4.0473","volume":"52","author":"W Young","year":"1980","unstructured":"Young, W., DeCrescito, V., Tomasula, J.J. & Ho, V. The role of the sympathetic nervous system in pressor responses induced by spinal injury. J. Neurosurg. 52, 473\u2013481 (1980).","journal-title":"J. Neurosurg."},{"key":"BFnn4643_CR29","first-page":"291","volume":"183","author":"AV Edwards","year":"1993","unstructured":"Edwards, A.V. & Jones, C.T. Autonomic control of adrenal function. J. Anat. 183, 291\u2013307 (1993).","journal-title":"J. Anat."},{"key":"BFnn4643_CR30","first-page":"265","volume":"183","author":"TL Parker","year":"1993","unstructured":"Parker, T.L., Kesse, W.K., Mohamed, A.A. & Afework, M. The innervation of the mammalian adrenal gland. J. Anat. 183, 265\u2013276 (1993).","journal-title":"J. Anat."},{"key":"BFnn4643_CR31","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1749-6632.1987.tb24980.x","volume":"512","author":"MA Holzwarth","year":"1987","unstructured":"Holzwarth, M.A., Cunningham, L.A. & Kleitman, N. The role of adrenal nerves in the regulation of adrenocortical functions. Ann. NY Acad. Sci. 512, 449\u2013464 (1987).","journal-title":"Ann. NY Acad. Sci."},{"key":"BFnn4643_CR32","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1073\/pnas.96.3.1059","volume":"96","author":"FS Dhabhar","year":"1999","unstructured":"Dhabhar, F.S. & McEwen, B.S. Enhancing versus suppressive effects of stress hormones on skin immune function. Proc. Natl. Acad. Sci. USA 96, 1059\u20131064 (1999).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnn4643_CR33","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1084\/jem.20120571","volume":"209","author":"U Andersson","year":"2012","unstructured":"Andersson, U. & Tracey, K.J. Neural reflexes in inflammation and immunity. J. Exp. Med. 209, 1057\u20131068 (2012).","journal-title":"J. Exp. Med."},{"key":"BFnn4643_CR34","doi-asserted-by":"crossref","first-page":"5134","DOI":"10.1182\/blood-2008-11-190769","volume":"113","author":"S Dimitrov","year":"2009","unstructured":"Dimitrov, S. et al. Cortisol and epinephrine control opposing circadian rhythms in T cell subsets. Blood 113, 5134\u20135143 (2009).","journal-title":"Blood"},{"key":"BFnn4643_CR35","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.immuni.2012.05.021","volume":"37","author":"C Scheiermann","year":"2012","unstructured":"Scheiermann, C. et al. Adrenergic nerves govern circadian leukocyte recruitment to tissues. Immunity 37, 290\u2013301 (2012).","journal-title":"Immunity"},{"key":"BFnn4643_CR36","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4049\/jimmunol.156.1.93","volume":"156","author":"M Schedlowski","year":"1996","unstructured":"Schedlowski, M. et al. Catecholamines modulate human NK cell circulation and function via spleen-independent beta 2-adrenergic mechanisms. J. Immunol. 156, 93\u201399 (1996).","journal-title":"J. Immunol."},{"key":"BFnn4643_CR37","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1084\/jem.20021098","volume":"198","author":"K Prass","year":"2003","unstructured":"Prass, K. et al. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J. Exp. Med. 198, 725\u2013736 (2003).","journal-title":"J. Exp. Med."},{"key":"BFnn4643_CR38","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.expneurol.2007.05.019","volume":"207","author":"KM Lucin","year":"2007","unstructured":"Lucin, K.M., Sanders, V.M., Jones, T.B., Malarkey, W.B. & Popovich, P.G. Impaired antibody synthesis after spinal cord injury is level dependent and is due to sympathetic nervous system dysregulation. Exp. Neurol. 207, 75\u201384 (2007).","journal-title":"Exp. Neurol."},{"key":"BFnn4643_CR39","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1089\/neu.2006.0117","volume":"24","author":"P Rouleau","year":"2007","unstructured":"Rouleau, P., Ung, R.V., Lapointe, N.P. & Guertin, P.A. Hormonal and immunological changes in mice after spinal cord injury. J. Neurotrauma 24, 367\u2013378 (2007).","journal-title":"J. Neurotrauma"},{"key":"BFnn4643_CR40","doi-asserted-by":"crossref","first-page":"287","DOI":"10.3109\/10739689609148303","volume":"3","author":"UH von Andrian","year":"1996","unstructured":"von Andrian, U.H. Intravital microscopy of the peripheral lymph node microcirculation in mice. Microcirculation 3, 287\u2013300 (1996).","journal-title":"Microcirculation"},{"key":"BFnn4643_CR41","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/1471-2377-13-168","volume":"13","author":"MA Kopp","year":"2013","unstructured":"Kopp, M.A. et al. The SCIentinel study--prospective multicenter study to define the spinal cord injury-induced immune depression syndrome (SCI-IDS)--study protocol and interim feasibility data. BMC Neurol. 13, 168 (2013).","journal-title":"BMC Neurol."},{"key":"BFnn4643_CR42","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/sc.2015.176","volume":"54","author":"G Fatima","year":"2016","unstructured":"Fatima, G., Sharma, V.P. & Verma, N.S. Circadian variations in melatonin and cortisol in patients with cervical spinal cord injury. Spinal Cord 54, 364\u2013367 (2016).","journal-title":"Spinal Cord"}],"container-title":["Nature Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nn.4643.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nn.4643","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/nn.4643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nn.4643.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T20:43:36Z","timestamp":1692996216000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nn.4643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,18]]},"references-count":42,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["BFnn4643"],"URL":"https:\/\/doi.org\/10.1038\/nn.4643","relation":{},"ISSN":["1097-6256","1546-1726"],"issn-type":[{"value":"1097-6256","type":"print"},{"value":"1546-1726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,18]]},"assertion":[{"value":"5 April 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}