{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:51:58Z","timestamp":1786981918419,"version":"build-2736575974"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008414","name":"University of Canterbury","doi-asserted-by":"crossref","award":["UC Doctoral Scholarship"],"award-info":[{"award-number":["UC Doctoral Scholarship"]}],"id":[{"id":"10.13039\/100008414","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014437","name":"Wenner-Gren Stiftelserna","doi-asserted-by":"publisher","award":["WGF2022-0044"],"award-info":[{"award-number":["WGF2022-0044"]}],"id":[{"id":"10.13039\/100014437","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006353","name":"Kjell och M\u00e4rta Beijers Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006353","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008414","name":"University of Canterbury","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008414","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Bull Math Biol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mechanical ventilation is a life support system for patients with acute respiratory distress syndrome (ARDS). As part of strategies to protect the lung during ventilation, plateau pressure can be determined via an end-inspiratory pause; however, there is no agreed-upon pause duration in medical protocols. Mechanical ventilation can be modelled using the Viscoelastic model (VEM) for respiration. The identification of static compliance is of clinical interest, as it can be used to estimate plateau pressure. Practical identifiability analysis quantifies the confidence with which model parameters can be estimated from finite, noisy data. This paper evaluates the robustness of plateau pressure estimates in clinical data by analysing practical identifiability of the VEM identified in data with varying durations of end expiratory pauses. Profile likelihood and Hamiltonian Monte Carlo (HMC) simulations were used to determine estimation robustness. The methods were\u00a0applied to mechanical ventilation data from a previous ARDS study. Profile likelihood and HMC showed strong agreement in both parameter estimates and identifiability results with similar confidence distributions. Both methods demonstrated a loss of parameter robustness that would preclude clinical utility when the end expiratory pause was reduced. By quantifying the confidence in parameter estimation and finding trade-offs in parameters that may be previously unknown when parameters are estimated, the methods give insight into the certainty of the estimate and parameter behaviours, even when the model fits the data well.<\/jats:p>","DOI":"10.1007\/s11538-025-01497-z","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T15:50:39Z","timestamp":1754495439000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Practical Identifiability in a Viscoelastic Respiratory Model for Mechanical Ventilation"],"prefix":"10.1007","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3908-8795","authenticated-orcid":false,"given":"A. E.","family":"Cerdeira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5001-6148","authenticated-orcid":false,"given":"N. N.","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1105-8078","authenticated-orcid":false,"given":"S.","family":"Hamis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1661-2573","authenticated-orcid":false,"given":"P. D.","family":"Docherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"issue":"6","key":"1497_CR1","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1056\/NEJM199802053380602","volume":"338","author":"MBP Amato","year":"1998","unstructured":"Amato MBP, Barbas CSV, Medeiros DM et al (1998) Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 338(6):347\u2013354. https:\/\/doi.org\/10.1056\/NEJM199802053380602","journal-title":"N Engl J Med"},{"key":"1497_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2022.106275","volume":"151","author":"CYS Ang","year":"2022","unstructured":"Ang CYS, Chiew YS, Wang X, Mat Nor MB, Cove ME, Chase JG (2022) Predicting mechanically ventilated patients future respiratory system elastance \u2013 a stochastic modelling approach. Comput Biol Med 151:106275. https:\/\/doi.org\/10.1016\/j.compbiomed.2022.106275","journal-title":"Comput Biol Med"},{"issue":"1","key":"1497_CR3","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1007\/s00134-002-1568-z","volume":"29","author":"L Barberis","year":"2003","unstructured":"Barberis L, Manno E, Gu\u00e9rin C (2003) Effect of end-inspiratory pause duration on plateau pressure in mechanically ventilated patients. Intensive Care Med 29(1):130\u2013134. https:\/\/doi.org\/10.1007\/s00134-002-1568-z","journal-title":"Intensive Care Med"},{"key":"1497_CR4","doi-asserted-by":"publisher","unstructured":"Bates JHT (2009) Lung mechanics: an inverse modeling approach\/Jason H. T. Bates. [Online]. https:\/\/doi.org\/10.1017\/CBO9780511627156","DOI":"10.1017\/CBO9780511627156"},{"issue":"3","key":"1497_CR5","first-page":"243","volume":"21","author":"P Battistella","year":"1985","unstructured":"Battistella P, Delorme N, Sadoul P, Polu JM (1985) Effect of artificial ventilation with an end-expiratory plateau on gas exchange amd hemodynamics in chronic respiratory failure. Bull Eur Physiopathol Respir 21(3):243\u2013250","journal-title":"Bull Eur Physiopathol Respir"},{"issue":"1","key":"1497_CR6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/MCC.0000000000000579","volume":"25","author":"JR Beitler","year":"2019","unstructured":"Beitler JR (2019) Bedside respiratory physiology to detect risk of lung injury in acute respiratory distress syndrome. Curr Opin Crit Care 25(1):3\u201311. https:\/\/doi.org\/10.1097\/MCC.0000000000000579","journal-title":"Curr Opin Crit Care"},{"key":"1497_CR7","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/B978-075067572-7.50032-1","volume-title":"Cardiothoracic critical care","author":"D Buckley","year":"2007","unstructured":"Buckley D, Gillham M (2007) Chapter 29\u2014Invasive respiratory support. In: Sidebotham D, Mckee A, Gillham M, Levy JH (eds) Cardiothoracic critical care. Butterworth-Heinemann, pp 419\u2013436. https:\/\/doi.org\/10.1016\/B978-075067572-7.50032-1"},{"key":"1497_CR8","unstructured":"Dickson JL, Gunn CA, Chase JG (2014) Humans are horribly variable. Int J Clin Med Images 1(2). Accessed November 17, 2024. https:\/\/www.imagejournals.org\/articles\/humans-are-horribly-variable-32.html"},{"issue":"4","key":"1497_CR9","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1007\/BF02886698","volume":"9","author":"D Hess","year":"1993","unstructured":"Hess D, Tabor T (1993) Comparison of six methods to calculate airway resistance during mechanical ventilation in adults. J Clin Monit 9(4):275\u2013282. https:\/\/doi.org\/10.1007\/BF02886698","journal-title":"J Clin Monit"},{"key":"1497_CR10","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.matcom.2022.03.020","volume":"199","author":"NN Lam","year":"2022","unstructured":"Lam NN, Docherty PD, Murray R (2022) Practical identifiability of parametrised models: a review of benefits and limitations of various approaches. Math Comput Simul 199:202\u2013216. https:\/\/doi.org\/10.1016\/j.matcom.2022.03.020","journal-title":"Math Comput Simul"},{"issue":"6","key":"1497_CR11","doi-asserted-by":"publisher","DOI":"10.1007\/s11538-024-01304-1","volume":"86","author":"NN Lam","year":"2024","unstructured":"Lam NN, Murray R, Docherty PD (2024) Evolving improved sampling protocols for dose-response modelling using genetic algorithms with a profile-likelihood metric. Bull Math Biol 86(6):70. https:\/\/doi.org\/10.1007\/s11538-024-01304-1","journal-title":"Bull Math Biol"},{"key":"1497_CR12","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.bspc.2016.01.010","volume":"27","author":"R Langdon","year":"2016","unstructured":"Langdon R, Docherty PD, Chiew YS, M\u00f6ller K, Chase JG (2016) Use of basis functions within a non-linear autoregressive model of pulmonary mechanics. Biomed Signal Process Control 27:44\u201350. https:\/\/doi.org\/10.1016\/j.bspc.2016.01.010","journal-title":"Biomed Signal Process Control"},{"issue":"1","key":"1497_CR13","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s12553-016-0172-0","volume":"7","author":"B Laufer","year":"2017","unstructured":"Laufer B, Kretschmer J, Docherty PD, Chiew YS, M\u00f6ller K (2017) Lung mechanics - airway resistance in the dynamic elastance model. Health Technol 7(1):61\u201370. https:\/\/doi.org\/10.1007\/s12553-016-0172-0","journal-title":"Health Technol"},{"key":"1497_CR14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.coisb.2019.10.006","volume":"18","author":"ED Mitra","year":"2019","unstructured":"Mitra ED, Hlavacek WS (2019) Parameter estimation and uncertainty quantification for systems biology models. Curr Opin Syst Biol 18:9\u201318. https:\/\/doi.org\/10.1016\/j.coisb.2019.10.006","journal-title":"Curr Opin Syst Biol"},{"key":"1497_CR15","unstructured":"Mora Carpio AL, Mora JI (2024) Ventilator management. In: StatPearls. StatPearls Publishing. Accessed November 17, 2024. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK448186\/"},{"key":"1497_CR16","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.arcontrol.2019.05.001","volume":"48","author":"SE Morton","year":"2019","unstructured":"Morton SE, Knopp JL, Chase JG et al (2019) Optimising mechanical ventilation through model-based methods and automation. Annu Rev Control 48:369\u2013382. https:\/\/doi.org\/10.1016\/j.arcontrol.2019.05.001","journal-title":"Annu Rev Control"},{"issue":"1","key":"1497_CR17","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1186\/s13054-021-03686-3","volume":"25","author":"P Pelosi","year":"2021","unstructured":"Pelosi P, Ball L, Barbas CSV et al (2021) Personalized mechanical ventilation in acute respiratory distress syndrome. Crit Care 25(1):250. https:\/\/doi.org\/10.1186\/s13054-021-03686-3","journal-title":"Crit Care"},{"issue":"15","key":"1497_CR18","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1093\/bioinformatics\/btp358","volume":"25","author":"A Raue","year":"2009","unstructured":"Raue A, Kreutz C, Maiwald T et al (2009) Structural and practical identifiability analysis of partially observed dynamical models by exploiting the profile likelihood. Bioinformatics 25(15):1923\u20131929. https:\/\/doi.org\/10.1093\/bioinformatics\/btp358","journal-title":"Bioinformatics"},{"issue":"1","key":"1497_CR19","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/1475-925X-11-38","volume":"11","author":"C Schranz","year":"2012","unstructured":"Schranz C, Docherty PD, Chiew YS, M\u00f6ller K, Chase JG (2012) Iterative integral parameter identification of a respiratory mechanics model. Biomed Eng OnLine 11(1):38. https:\/\/doi.org\/10.1186\/1475-925X-11-38","journal-title":"Biomed Eng OnLine"},{"key":"1497_CR20","unstructured":"Schwarz D (2024) Fast and robust curve intersections. Accessed November 17, 2024. https:\/\/au.mathworks.com\/matlabcentral\/fileexchange\/11837-fast-and-robust-curve-intersections"},{"issue":"1","key":"1497_CR21","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s40635-023-00569-5","volume":"11","author":"PL Silva","year":"2023","unstructured":"Silva PL, Scharffenberg M, Rocco PRM (2023) Understanding the mechanisms of ventilator-induced lung injury using animal models. Intensive Care Med Exp 11(1):82. https:\/\/doi.org\/10.1186\/s40635-023-00569-5","journal-title":"Intensive Care Med Exp"},{"issue":"164","key":"1497_CR22","doi-asserted-by":"publisher","first-page":"20200055","DOI":"10.1098\/rsif.2020.0055","volume":"17","author":"MJ Simpson","year":"2020","unstructured":"Simpson MJ, Baker RE, Vittadello ST, Maclaren OJ (2020) Practical parameter identifiability for spatio-temporal models of cell invasion. J R Soc Interface 17(164):20200055. https:\/\/doi.org\/10.1098\/rsif.2020.0055","journal-title":"J R Soc Interface"},{"issue":"22","key":"1497_CR23","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1056\/NEJMra1208707","volume":"369","author":"AS Slutsky","year":"2013","unstructured":"Slutsky AS, Ranieri VM (2013) Ventilator-induced lung injury. N Engl J Med 369(22):2126\u20132136. https:\/\/doi.org\/10.1056\/NEJMra1208707","journal-title":"N Engl J Med"},{"issue":"8","key":"1497_CR24","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1097\/01.CCM.0000227220.67613.0D","volume":"34","author":"CA Stahl","year":"2006","unstructured":"Stahl CA, M\u00f6ller K, Schumann S et al (2006) Dynamic versus static respiratory mechanics in acute lung injury and acute respiratory distress syndrome. Crit Care Med 34(8):2090. https:\/\/doi.org\/10.1097\/01.CCM.0000227220.67613.0D","journal-title":"Crit Care Med"},{"key":"1497_CR25","unstructured":"Stan Development Team. Stan. Published online December 10, 2024. https:\/\/mc-stan.org"},{"key":"1497_CR26","unstructured":"Stan Development Team. RStan: the R interface to Stan. Published online 2024. https:\/\/mc-stan.org"},{"key":"1497_CR27","unstructured":"Stan Development Team. Stan Reference Manual, Version 2.36. MCMC Sampling. 2025. Accessed May 21, 2025. https:\/\/mc-stan.org\/docs\/reference-manual\/mcmc.html"},{"issue":"15","key":"1497_CR28","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.ifacol.2021.10.243","volume":"54","author":"Q Sun","year":"2021","unstructured":"Sun Q, Chase JG, Zhou C et al (2021) Minimal lung mechanics basis-functions for a mechanical ventilation virtual patient. IFAC-PapersOnLine 54(15):127\u2013132. https:\/\/doi.org\/10.1016\/j.ifacol.2021.10.243","journal-title":"IFAC-PapersOnLine"},{"key":"1497_CR29","unstructured":"The MathWorks Inc. MATLAB version: 24.1.0.2628055 (R2024a). Published online 2024. https:\/\/www.mathworks.com"},{"issue":"1","key":"1497_CR30","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3758\/s13423-016-1015-8","volume":"25","author":"D van Ravenzwaaij","year":"2016","unstructured":"van Ravenzwaaij D, Cassey P, Brown SD (2016) A simple introduction to Markov Chain Monte-Carlo sampling. Psychon Bull Rev 25(1):143. https:\/\/doi.org\/10.3758\/s13423-016-1015-8","journal-title":"Psychon Bull Rev"},{"key":"1497_CR31","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s11538-025-01415-3","volume":"87","author":"A Villaverde","year":"2025","unstructured":"Villaverde A (2025) Employing observability rank conditions for taking into account experimental information a priori. Bull Math Biol 87:39. https:\/\/doi.org\/10.1007\/s11538-025-01415-3","journal-title":"Bull Math Biol"},{"issue":"10","key":"1497_CR32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005153","volume":"12","author":"AF Villaverde","year":"2016","unstructured":"Villaverde AF, Barreiro A, Papachristodoulou A (2016) Structural identifiability of dynamic systems biology models. PLoS Comput Biol 12(10):e1005153. https:\/\/doi.org\/10.1371\/journal.pcbi.1005153","journal-title":"PLoS Comput Biol"},{"key":"1497_CR33","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/B978-1-4377-2764-7.00048-8","volume-title":"Benumof and Hagberg\u2019s airway management","author":"MA Warner","year":"2013","unstructured":"Warner MA, Patel B (2013) Chapter 48\u2014Mechanical ventilation. In: Hagberg CA (ed) Benumof and Hagberg\u2019s airway management, 3rd edn. WB Saunders, Berlin, pp 981-997.e3. https:\/\/doi.org\/10.1016\/B978-1-4377-2764-7.00048-8","edition":"3"},{"key":"1497_CR34","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.coisb.2021.03.005","volume":"25","author":"FG Wieland","year":"2021","unstructured":"Wieland FG, Hauber AL, Rosenblatt M, T\u00f6nsing C, Timmer J (2021) On structural and practical identifiability. Curr Opin Syst Biol 25:60\u201369. https:\/\/doi.org\/10.1016\/j.coisb.2021.03.005","journal-title":"Curr Opin Syst Biol"}],"container-title":["Bulletin of Mathematical Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11538-025-01497-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11538-025-01497-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11538-025-01497-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T06:50:12Z","timestamp":1756623012000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11538-025-01497-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":34,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["1497"],"URL":"https:\/\/doi.org\/10.1007\/s11538-025-01497-z","relation":{},"ISSN":["0092-8240","1522-9602"],"issn-type":[{"value":"0092-8240","type":"print"},{"value":"1522-9602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,6]]},"assertion":[{"value":"17 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"122"}}