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Publications (10 of 20) Show all publications
Vikström, A., Eklund, A., Johannesdottir, M., Wåhlin, A., Zarrinkoob, L., Malm, J., . . . Holmlund, P. (2025). Non-invasive assessment of cerebral perfusion pressure: Applied towards preoperative planning of aortic arch surgery with selective antegrade cerebral perfusion. Journal of Biomechanics, 179, Article ID 112459.
Open this publication in new window or tab >>Non-invasive assessment of cerebral perfusion pressure: Applied towards preoperative planning of aortic arch surgery with selective antegrade cerebral perfusion
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2025 (English)In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 179, article id 112459Article in journal (Refereed) Published
Abstract [en]

Selective antegrade cerebral perfusion (SACP) is a protective procedure to ascertain adequate brain perfusion during aortic arch surgeries requiring moderate hypothermic circulatory arrest. SACP entails catheterization of arteries feeding the brain, which can be done bilaterally (bSACP) or unilaterally (uSACP), but there is no consensus on when to use each approach. bSACP may increase the risk of embolization, while uSACP risks hypoperfusion due to insufficient perfusion pressure in the contralateral hemisphere, since a single catheter must perfuse both hemispheres. We developed and tested the feasibility of a new method for predicting cerebral perfusion pressures (CPP) during SACP, which could potentially aid clinicians in preoperatively identifying which SACP approach to use. Feasibility of the method was evaluated in five patients eligible for aortic arch surgery (65 ± 7 years, 3 men). Patients were investigated preoperatively with computed tomography angiography (CTA) and 4D flow magnetic resonance imaging (MRI) to assess patient-specific arterial anatomy and blood flows. From the imaging, computational fluid dynamics (CFD) simulations estimated the patients' vascular resistances. Applying these resistances and intraoperative SACP pressure/flow settings to the model's boundary conditions allowed for predictions of contralateral CPP during SACP. Predicted pressures were compared to corresponding intraoperative pressure measurements. The method showed promise for predicting contralateral CPP during both uSACP (median error (range): 2.4 (−0.2–18.0) mmHg) and bSACP (0.8 (−3.3–5.4) mmHg). Predictions were most sensitive to collateral artery size. This study showed the feasibility of CPP predictions of SACP, and presents key features needed for accurate modelling.

Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
4D flow MRI, Aortic arch surgery, Cerebral perfusion pressure, Computational fluid dynamics, Selective antegrade cerebral perfusion
National Category
Surgery Physiology and Anatomy
Identifiers
urn:nbn:se:umu:diva-233313 (URN)10.1016/j.jbiomech.2024.112459 (DOI)001383269200001 ()39662261 (PubMedID)2-s2.0-85211374967 (Scopus ID)
Funder
Region Västerbotten
Available from: 2025-01-03 Created: 2025-01-03 Last updated: 2025-02-10Bibliographically approved
Kristiansen, M., Holmlund, P., Linden, C., Eklund, A. & Jóhannesson, G. (2024). Author response: deficient optic nerve sheath occlusion in ntg patients: optic nerve damage due to translaminar pressure imbalance, glymphatic failure, or both? [Letter to the editor]. Investigative Ophthalmology and Visual Science, 65(5), Article ID 19.
Open this publication in new window or tab >>Author response: deficient optic nerve sheath occlusion in ntg patients: optic nerve damage due to translaminar pressure imbalance, glymphatic failure, or both?
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2024 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 65, no 5, article id 19Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology (ARVO), 2024
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-224851 (URN)10.1167/iovs.65.5.19 (DOI)001242507100005 ()38717422 (PubMedID)2-s2.0-85192594501 (Scopus ID)
Available from: 2024-06-11 Created: 2024-06-11 Last updated: 2025-04-24Bibliographically approved
Vikström, A., Holmlund, P., Holmgren, M., Wåhlin, A., Zarrinkoob, L., Malm, J. & Eklund, A. (2024). Establishing the distribution of cerebrovascular resistance using computational fluid dynamics and 4D flow MRI. Scientific Reports, 14(1), Article ID 14585.
Open this publication in new window or tab >>Establishing the distribution of cerebrovascular resistance using computational fluid dynamics and 4D flow MRI
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2024 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 14585Article in journal (Refereed) Published
Abstract [en]

Cerebrovascular resistance (CVR) regulates blood flow in the brain, but little is known about the vascular resistances of the individual cerebral territories. We present a method to calculate these resistances and investigate how CVR varies in the hemodynamically disturbed brain. We included 48 patients with stroke/TIA (29 with symptomatic carotid stenosis). By combining flow rate (4D flow MRI) and structural computed tomography angiography (CTA) data with computational fluid dynamics (CFD) we computed the perfusion pressures out from the circle of Willis, with which CVR of the MCA, ACA, and PCA territories was estimated. 56 controls were included for comparison of total CVR (tCVR). CVR were 33.8 ± 10.5, 59.0 ± 30.6, and 77.8 ± 21.3 mmHg s/ml for the MCA, ACA, and PCA territories. We found no differences in tCVR between patients, 9.3 ± 1.9 mmHg s/ml, and controls, 9.3 ± 2.0 mmHg s/ml (p = 0.88), nor in territorial CVR in the carotid stenosis patients between ipsilateral and contralateral hemispheres. Territorial resistance associated inversely to territorial brain volume (p < 0.001). These resistances may work as reference values when modelling blood flow in the circle of Willis, and the method can be used when there is need for subject-specific analysis.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Neurosciences Physiology and Anatomy Medical Imaging Computational Mathematics
Identifiers
urn:nbn:se:umu:diva-227152 (URN)10.1038/s41598-024-65431-4 (DOI)001255006800068 ()2-s2.0-85196758949 (Scopus ID)
Funder
Swedish Research Council, 2015-05616Swedish Research Council, 2017-04949Region VästerbottenSwedish Heart Lung FoundationSwedish Foundation for Strategic Research
Available from: 2024-06-25 Created: 2024-06-25 Last updated: 2025-04-24Bibliographically approved
Kristiansen, M., Holmlund, P., Linden, C., Eklund, A. & Jóhannesson, G. (2023). Optic nerve subarachnoid space posture dependency: an MRI study in subjects with normal tension glaucoma and healthy controls. Investigative Ophthalmology and Visual Science, 64(15), Article ID 20.
Open this publication in new window or tab >>Optic nerve subarachnoid space posture dependency: an MRI study in subjects with normal tension glaucoma and healthy controls
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2023 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 64, no 15, article id 20Article in journal (Refereed) Published
Abstract [en]

Purpose: The purpose of this study was to examine the differences of optic nerve subarachnoid space (ONSAS) volume in patients with normal tension glaucoma (NTG) and healthy controls in different body positions.

Methods: Eight patients with NTG and seven healthy controls underwent magnetic resonance imaging (MRI) examinations in head up tilt (HUT) +11 degrees and head down tilt (HDT) -5 degrees positions according to a randomized protocol determining the starting position. The ONSAS volume in both body positions was measured and compared between the two groups. The results were analyzed using a generalized linear model.

Results: Between HDT and HUT, the postural ONSAS volume change was dependent on starting position (P < 0.001) and group (P = 0.003, NTG versus healthy). A subgroup analysis of those that were randomized to HUT examination first, coming directly from an upright position, showed that the patients with NTG had significantly larger positional ONSAS volume changes compared to the healthy controls; 121 ± 22 µL vs. 65 ± 37 µL (P = 0.049). Analysis of the ONSAS volume distribution showed different profiles for patients with NTG and healthy controls.

Conclusions: There was a significant difference in ONSAS volume change between patients with NTG and healthy subjects when subjected to posture changes, specifically when going from upright to head-down posture. This indicates that patients with NTG had been exposed to a lower ONSAS pressure when they came from the upright posture, which suggests an increased translaminar pressure difference in upright position. This may support the theory that NTG has a dysfunction in an occlusion mechanism of the optic nerve sheath that could cause abnormally negative ONSAS pressures in upright posture.

Keywords
optic nerve subarachnoid space (ONSAS), glaucoma
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-218636 (URN)10.1167/iovs.64.15.20 (DOI)001169546400015 ()38099734 (PubMedID)2-s2.0-85179765988 (Scopus ID)
Available from: 2023-12-27 Created: 2023-12-27 Last updated: 2025-04-24Bibliographically approved
Holmlund, P., Stoverud, K.-H. & Eklund, A. (2022). Mathematical modelling of the CSF system: effects of microstructures and posture on optic nerve subarachnoid space dynamics. Fluids and Barriers of the CNS, 19(1), Article ID 67.
Open this publication in new window or tab >>Mathematical modelling of the CSF system: effects of microstructures and posture on optic nerve subarachnoid space dynamics
2022 (English)In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 19, no 1, article id 67Article in journal (Refereed) Published
Abstract [en]

Background: The pressure difference between the eye and brain in upright postures may be affected by compartmentalization of the optic nerve subarachnoid space (ONSAS). Both pressure and deformation will depend on the microstructures of the ONSAS, and most likely also on ocular glymphatic clearance. Studying these factors could yield important knowledge regarding the translaminar pressure difference, which is suspected to play a role in normal-tension glaucoma.

Methods: A compartment model coupling the ONSAS with the craniospinal CSF system was used to investigate the effects of microstructures on the pressure transfer through the ONSAS during a posture change from supine to upright body postures. ONSAS distensibility was based on MRI measurements. We also included ocular glymphatic flow to investigate how local pressure gradients alter this flow with changes in posture.

Results: A compartmentalization of the ONSAS occurred in the upright posture, with ONSAS porosity (degree of microstructural content) affecting the ONSAS pressure (varying the supine/baseline porosity from 1.0 to 0.75 yielded pressures between − 5.3 and − 2 mmHg). Restricting the minimum computed porosity (occurring in upright postures) to 0.3 prevented compartmentalization, and the ONSAS pressure could equilibrate with subarachnoid space pressure (− 6.5 mmHg) in ≤ 1 h. The ocular glymphatics analysis predicted that substantial intraocular-CSF flows could occur without substantial changes in the ONSAS pressure. The flow entering the ONSAS in supine position (both from the intraocular system and from the cranial subarachnoid space) exited the ONSAS through the optic nerve sheath, while in upright postures the flow through the ONSAS was redirected towards the cranial subarachnoid space.

Conclusions: Microstructures affect pressure transmission along the ONSAS, potentially contributing to ONSAS compartmentalization in upright postures. Different pathways for ocular glymphatic flow were predicted for different postures.

Place, publisher, year, edition, pages
BioMed Central, 2022
Keywords
Compartmentalization, CSF dynamics, Glaucoma, Numerical modelling, Ocular glymphatics, Optic nerve subarachnoid space, Posture, Translaminar pressure
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-199397 (URN)10.1186/s12987-022-00366-4 (DOI)000847690800001 ()36042452 (PubMedID)2-s2.0-85136948726 (Scopus ID)
Funder
Swedish National Space Board, 193/17Swedish Foundation for Strategic Research
Available from: 2022-09-21 Created: 2022-09-21 Last updated: 2024-01-17Bibliographically approved
Nilsson, D., Holmgren, M., Holmlund, P., Wåhlin, A., Eklund, A., Dahlberg, T., . . . Andersson, M. (2022). Patient-specific brain arteries molded as a flexible phantom model using 3D printed water-soluble resin. Scientific Reports, 12, Article ID 10172.
Open this publication in new window or tab >>Patient-specific brain arteries molded as a flexible phantom model using 3D printed water-soluble resin
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2022 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, article id 10172Article in journal (Refereed) Published
Abstract [en]

Visualizing medical images from patients as physical 3D models (phantom models) have many roles in the medical field, from education to preclinical preparation and clinical research. However, current phantom models are generally generic, expensive, and time-consuming to fabricate. Thus, there is a need for a cost- and time-efficient pipeline from medical imaging to patient-specific phantom models. In this work, we present a method for creating complex 3D sacrificial molds using an off-the-shelf water-soluble resin and a low-cost desktop 3D printer. This enables us to recreate parts of the cerebral arterial tree as a full-scale phantom model (10×6×410×6×4 cm) in transparent silicone rubber (polydimethylsiloxane, PDMS) from computed tomography angiography images (CTA). We analyzed the model with magnetic resonance imaging (MRI) and compared it with the patient data. The results show good agreement and smooth surfaces for the arteries. We also evaluate our method by looking at its capability to reproduce 1 mm channels and sharp corners. We found that round shapes are well reproduced, whereas sharp features show some divergence. Our method can fabricate a patient-specific phantom model with less than 2 h of total labor time and at a low fabrication cost.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022
National Category
Orthopaedics Other Physics Topics Medical Imaging Other Medical Engineering
Identifiers
urn:nbn:se:umu:diva-195731 (URN)10.1038/s41598-022-14279-7 (DOI)000812565400068 ()2-s2.0-85132118240 (Scopus ID)
Funder
Swedish Research Council, 2019-04016
Available from: 2022-06-03 Created: 2022-06-03 Last updated: 2025-02-09Bibliographically approved
Holmgren, M., Holmlund, P., Stoverud, K.-H., Zarrinkoob, L., Wåhlin, A., Malm, J. & Eklund, A. (2022). Prediction of cerebral perfusion pressure during carotid surgery: A computational fluid dynamics approach. Clinical Biomechanics, 100, Article ID 105827.
Open this publication in new window or tab >>Prediction of cerebral perfusion pressure during carotid surgery: A computational fluid dynamics approach
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2022 (English)In: Clinical Biomechanics, ISSN 0268-0033, E-ISSN 1879-1271, Vol. 100, article id 105827Article in journal (Refereed) Published
Abstract [en]

Background: Maintaining cerebral perfusion pressure in the brain when a carotid artery is closed during vascular surgery is critical for avoiding intraoperative hypoperfusion and risk of ischemic stroke. Here we propose and evaluate a method based on computational fluid dynamics for predicting patient-specific cerebral perfusion pressures at carotid clamping during carotid endarterectomy.

Methods: The study consisted of 22 patients with symptomatic carotid stenosis who underwent carotid endarterectomy (73 ± 5 years, 59–80 years, 17 men). The geometry of the circle of Willis was obtained preoperatively from computed tomography angiography and corresponding flow rates from four-dimensional flow magnetic resonance imaging. The patients were also classified as having a present or absent ipsilateral posterior communicating artery based on computed tomography angiography. The predicted mean stump pressures from computational fluid dynamics were compared with intraoperatively measured stump pressures from carotid endarterectomy.

Findings: On group level, there was no difference between the predicted and measured stump pressures (−0.5 ± 13 mmHg, P = 0.86) and the pressures were correlated (r = 0.44, P = 0.039). Omitting two outliers, the correlation increased to r = 0.78 (P < 0.001) (−1.4 ± 8.0 mmHg, P = 0.45). Patients with a present ipsilateral posterior communicating artery (n = 8) had a higher measured stump pressure than those with an absent artery (n = 12) (P < 0.001).

Interpretation: The stump pressure agreement indicates that the computational fluid dynamics approach was promising in predicting cerebral perfusion pressures during carotid clamping, which may prove useful in the preoperative planning of vascular interventions.

Keywords
Carotid stenosis, Computational fluid dynamics, Endarterectomy, Ischemic stroke, Magnetic resonance imaging
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-201362 (URN)10.1016/j.clinbiomech.2022.105827 (DOI)000926947300006 ()2-s2.0-85142357306 (Scopus ID)
Funder
Swedish Research Council, 2015–05616Swedish Research Council, 2017–04949Region VästerbottenSwedish Heart Lung Foundation, 20140592
Available from: 2022-12-05 Created: 2022-12-05 Last updated: 2023-09-05Bibliographically approved
Holmlund, P., Stoverud, K.-H., Wahlin, A., Wiklund, U., Malm, J., Jóhannesson, G. & Eklund, A. (2021). Author Response: Posture-Dependent Collapse of the Optic Nerve Subarachnoid Space: A Combined MRI and Modeling Study [Letter to the editor]. Investigative Ophthalmology and Visual Science, 62(15), Article ID 15.
Open this publication in new window or tab >>Author Response: Posture-Dependent Collapse of the Optic Nerve Subarachnoid Space: A Combined MRI and Modeling Study
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2021 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 62, no 15, article id 15Article in journal, Letter (Other academic) Published
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-191394 (URN)10.1167/iovs.62.15.15 (DOI)000735528100001 ()34932065 (PubMedID)2-s2.0-85122376636 (Scopus ID)
Available from: 2022-01-17 Created: 2022-01-17 Last updated: 2024-01-15Bibliographically approved
Wåhlin, A., Holmlund, P., Fellows, A. M., Malm, J., Buckey, J. C. & Eklund, A. (2021). Optic Nerve Length before and after Spaceflight. Ophthalmology, 128(2), 309-316
Open this publication in new window or tab >>Optic Nerve Length before and after Spaceflight
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2021 (English)In: Ophthalmology, ISSN 0161-6420, E-ISSN 1549-4713, Vol. 128, no 2, p. 309-316Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The spaceflight-associated neuro-ocular syndrome (SANS) affects astronauts on missions to the International Space Station (ISS). The SANS has blurred vision and ocular changes as typical features. The objective of this study was to investigate if microgravity can create deformations or movements of the eye or optic nerve, and if such changes could be linked to SANS.

DESIGN: Cohort study.

PARTICIPANTS: Twenty-two astronauts (age 48 ± 4 years).

METHODS: The intervention consisted of time in microgravity at the ISS. We co-registered pre- and postspaceflight magnetic resonance imaging (MRI) scans and generated centerline representations of the optic nerve. The coordinates for the optic nerve head (ONH) and optic chiasm (OC) ends of the optic nerve were recorded along with the entire centerline path.

MAIN OUTCOME MEASURES: Optic nerve length, ONH movement, and OC movement after time in microgravity.

RESULTS: Optic nerve length increased (0.80 ± 0.74 mm, P < 0.001), primarily reflecting forward ONH displacement (0.63 ± 0.53 mm, P < 0.001). The forward displacement was positively related to mission duration, preflight body weight, and clinical manifestations of SANS. We also detected upward displacement of the OC (0.39 ± 0.50 mm, P = 0.002), indicative of brain movement, but this observation could not be linked to SANS.

CONCLUSIONS: The spaceflight-induced optic nerve lengthening and anterior movement of the ONH support that SANS is caused by an altered pressure difference between the brain and the eye, leading to a forward push on the posterior of the eye. Body weight is a potential contributing risk factor. Direct assessment of intracranial pressure in space is required to verify the implicated mechanism behind the ocular findings in SANS.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
Papilledema, idiopathic intracranial hypertension, intracranial pressure, magnetic resonance imaging, microgravity, optic nerve, space, spaceflight-associated neuro-ocular syndrome
National Category
Neurology Ophthalmology
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-178840 (URN)10.1016/j.ophtha.2020.07.007 (DOI)000609880500021 ()32659310 (PubMedID)2-s2.0-85089563023 (Scopus ID)
Note

Reply: Peter Wostyn, Charles Robert Gibson, Thomas H. Mader, Re: Wåhlin et al.: Optic nerve length before and after spaceflight (Ophthalmology. 2021;128:309–316), Ophthalmology, Volume 128, Issue 5,2021, Pages e27-e28, DOI: 10.1016/j.ophtha.2021.01.003

Reply: Anders Wåhlin, Petter Holmlund, Abigail M. Fellows, Jan Malm, Jay C. Buckey, Anders Eklund, Reply, Ophthalmology, Volume 128, Issue 5, 2021, Page e28. DOI: 10.1016/j.ophtha.2021.01.004

Available from: 2021-01-19 Created: 2021-01-19 Last updated: 2023-03-28Bibliographically approved
Holmlund, P., Stoverud, K.-H., Wåhlin, A., Wiklund, U., Malm, J., Jóhannesson, G. & Eklund, A. (2021). Posture-dependent collapse of the optic nerve subarachnoid space: A combined MRI and modeling study. Investigative Ophthalmology and Visual Science, 62(4), Article ID 26.
Open this publication in new window or tab >>Posture-dependent collapse of the optic nerve subarachnoid space: A combined MRI and modeling study
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2021 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 62, no 4, article id 26Article in journal (Refereed) Published
Abstract [en]

PURPOSE: We hypothesize that a collapse of the optic nerve subarachnoid space (ONSAS) in the upright posture may protect the eyes from large translamina cribrosa pressure differences (TLCPD) believed to play a role in various optic nerve diseases (e.g., glaucoma). In this study, we combined magnetic resonance imaging (MRI) and mathematical modeling to investigate this potential ONSAS collapse and its effects on the TLCPD.

METHODS: First, we performed MRI on six healthy volunteers in 6° head-down tilt (HDT) and 13° head-up tilt (HUT) to assess changes in ONSAS volume (measured from the eye to the optic canal) with changes in posture. The volume change reflects optic nerve sheath (ONS) distensibility. Second, we used the MRI data and mathematical modeling to simulate ONSAS pressure and the potential ONSAS collapse in a 90° upright posture.

RESULTS: The MRI showed a 33% decrease in ONSAS volume from the HDT to HUT (P < 0.001). In the upright posture, the simulations predicted an ONSAS collapse 25 mm behind lamina cribrosa, disrupting the pressure communication between the ONSAS and the intracranial subarachnoid space. The collapse reduced the simulated postural increase in TLCPD by roughly 1 mm Hg, although this reduction was highly sensitive to ONS distensibility, varying between 0 and 4.8 mm Hg when varying the distensibility by ± 1 SD.

CONCLUSIONS: The ONSAS volume along the optic nerve is posture dependent. The simulations supported the hypothesized ONSAS collapse in the upright posture and showed that even small changes in ONS stiffness/distensibility may affect the TLCPD.

Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology, 2021
Keywords
Glaucoma, Glymphatics, Optic nerve subarachnoid space, Posture, Translaminar pressure
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-183129 (URN)10.1167/iovs.62.4.26 (DOI)000696094600012 ()33877263 (PubMedID)2-s2.0-85104948743 (Scopus ID)
Funder
Swedish National Space Board, 193/17
Available from: 2021-05-17 Created: 2021-05-17 Last updated: 2024-01-15Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-1141-5143

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