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VOLUME 6, ISSUE 1 

 2023 

 

RESEARCH ARTICLE 

 

Arnstein T, Buis A. Methodology to investigate effect of prosthetic interface design on residual limb soft tissue deformation. Canadian Prosthetics & Orthotics 

Journal. 2023; Volume 6, Issue 1, No.7. https://doi.org/10.33137/cpoj.v6i1.42196 

 

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https://doi.org/10.33137/cpoj.v6i1.42196


 

1 

Arnstein T, Buis A. Methodology to investigate effect of prosthetic interface design on residual limb soft tissue deformation. Canadian Prosthetics & Orthotics 
Journal. 2023; Volume 6, Issue 1, No.7. https://doi.org/10.33137/cpoj.v6i1.42196 

 

 

RESEARCH ARTICLE 

 

METHODOLOGY TO INVESTIGATE EFFECT OF PROSTHETIC INTERFACE DESIGN ON 

RESIDUAL LIMB SOFT TISSUE DEFORMATION 

Arnstein T, Buis A* 

Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow, Scotland. 
 
  
 

 

 

 

  

 

 

 

 

 

 

 

 

 

 

INTRODUCTION   

For people living with amputation, use of a prosthetic device 

facilitates functional restoration of the missing limb. 

Ensuring safe load transfer between the prosthetic device 

and residual limb is critically important in successful 

rehabilitation. Improper loading at this interface can cause 

discomfort and injury to the user’s residual limb. This is a 

common experience for people living with lower limb 

amputation1-3 that can result in reduced prosthesis use or 

device rejection, limiting mobility and hence the ability of 

users  to  carry  out  activities of daily living.4,5 Furthermore,  

 

 

to remediate improper fit, additional devices are required to 

be manufactured placing increased strain on prosthetic care 

facilities and an additional burden on the user.1 As a result, 

improved interface design is consistently highlighted as a 

key requirement by prosthesis users worldwide.6 

The prosthetic interface describes the socket and liner. The 

geometry and mechanical characteristics of these 

components play a significant role in dictating how load is 

transferred between the prosthetic device and residual limb. 

Typically, a prosthetic socket is a quasi-rigid shell 

manufactured from a thermosetting or fibre-reinforced 

polymer. Sitting in between the socket and residual limb, the 

prosthetic liner is an elastomeric or foam sleeve that allows 

some level of adaptability to reduce interface pressure 

concentrations. To accommodate the unique geometry, 

features, and behaviour of each residual limb, prosthetic 

sockets must be custom made devices. Two distinct design 

 
OPEN  ACCESS 

ABSTRACT 

BACKGROUND: Residual limb discomfort and injury is a common experience for people living with lower 

limb amputation. Frequently, inadequate load distribution between the prosthetic device and the residual 

limb is the root cause of this issue. To advance our understanding of prosthetic interface fit, tools are needed 

to evaluate the mechanical interaction at the prosthetic interface, allowing interface designs to be evaluated 

and optimised. 

OBJECTIVES: Present a methodology report designed to facilitate comprehension of the mechanical 

interaction between the prosthetic interface and the residual limb. As a pilot study, this methodology is used 

to compare a hands-on and hands-off interface for a single transtibial prosthesis user using secondary 
Magnetic Resonance Imaging (MRI) data. 

METHODOLOGY: MRI data of the residual limb while wearing a prosthetic interface is segmented into a 

hard tissue and a skin surface model. These models are exported as stereolithography (STL) files. Two 

methods are used to analyse the interface designs. Firstly, CloudCompare software is used to compute the 

nearest vertex on the skin surface for every vertex on the compiled internal bony surface for both interface 

types. Secondly, CloudCompare software is used to compare registered skin surfaces of the residual limb 

while wearing the hands-on and hands-off interfaces. 

FINDINGS: The maximum and minimum nearest distances between the internal bony surface and skin 

surface were similar between interface types. However, the distribution of nearest distances was different. 

When comparing the skin surface while wearing both interfaces, where the fit is more compressive can be 

visualized. For the dataset used in this study, the classic features of a hands-on Patella Tendon Bearing 

interface and hands-off pressure cast interface could be identified. 

CONCLUSION: The methodology presented in this report may give researchers a further tool to better 

understand how interface designs affect the soft tissues of the residual limb. 

ARTICLE INFO 

Received: December 14, 2023 

Accepted: January 10, 2024 

Published: January 17, 2024 
 

CITATION 

Arnstein T, Buis A. Methodology 

to investigate effect of prosthetic 

interface design on residual limb 

soft tissue deformation. Canadian 

Prosthetics & Orthotics Journal. 

2023; Volume 6, Issue 1, No.7. 

https://doi.org/10.33137/cpoj.v6i1

.42196 

KEYWORDS 

Prosthetic, Interface, Socket, MRI, 

Tissue Strain, Deformation, Lower 

Limb Amputation, Residual Limb, 

Rehabilitation, Prosthesis, Tissue 

Deformation 

* CORRESPONDING AUTHOR: 

Arjan Buis, PhD  
Department of Biomedical Engineering, Faculty of Engineering, University 
of Strathclyde, Glasgow, Scotland. 

E-Mail: arjan.buis@strath.ac.uk 

ORCID ID: https://orcid.org/0000-0003-3947-293X 

Journal Homepage: https://jps.library.utoronto.ca/index.php/cpoj/index 

Volume 6, Issue 1, Article No.7. 2023 

 

 

https://doi.org/10.33137/cpoj.v6i1.42196
https://doi.org/10.33137/cpoj.v6i1.42196
https://doi.org/10.33137/cpoj.v6i1.42196
mailto:arjan.buis@strath.ac.uk
https://orcid.org/0000-0003-3947-293X
https://jps.library.utoronto.ca/index.php/cpoj/index


 

2 

Arnstein T, Buis A. Methodology to investigate effect of prosthetic interface design on residual limb soft tissue deformation. Canadian Prosthetics & Orthotics 
Journal. 2023; Volume 6, Issue 1, No.7. https://doi.org/10.33137/cpoj.v6i1.42196 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X EFFECT OF PROSTHETIC INTERFACE DESIGN ON RESIDUAL LIMB SOFT TISSUE DEFORMATION  
Arnstein T, and Buis A, 2023 

paradigms exist for prosthetic socket manufacture: hands-

on and hands-off casting.7,8 Hands-on casting refers to a 

clinician manually taking a cast of the residual limb and then 

rectifying this model to transfer load via purportedly load 

tolerant regions. Within the hands-on category, Computer 

Aided Design and Manufacture (CAD/CAM) is becoming 

more prevalent with CAD/CAM systems trying to replicate 

clinician best practice. Hands-off casting is where a 

pressurised vessel records the shape and volume that the 

residual limb takes. This method relies on the principle of 

hydrostatic load bearing whereby load is distributed across 

the residual limb more uniformly.9 Theoretically, under this 

condition, pressure gradients and peaks are reduced, and 

less tissue shear generated. 

Both hands-on and hands-off socket designs can achieve 

satisfactory clinical results.7,8 During prescription, interface 

fit is often assessed using tools that rely on user feedback 

and mobility performance testing.3,10 However, to develop 

more appropriate interface technology that is less likely to 

cause residual limb discomfort and injury, a better 

understanding of how socket design affects the mechanical 

conditions of the residual limb tissues is needed. Presently, 

researchers often measure interface pressure to compare 

socket designs.11-13 While indicative of the mechanical 

conditions at the skin surface, interface pressure cannot be 

used to understand the mechanical conditions of the 

internal tissues. 

To go beneath surface level and get a better understanding 

of body device interface fit, tissue strain has been proposed 

as an important metric owing to its significance in soft tissue 

injury aetiology.14-16 Within the tissues of the residual limb, 

strain can cause cellular death through direct mechanical 

insult, ischemia, reperfusion, and impaired lymphatic 

drainage.17 Researchers have presented tools to 

interrogate the internal mechanical conditions of soft 

tissues, within prosthetics and more widely the rehabilitation 

field.  

Finite Element Analysis (FEA) of the residual limb allows 

internal mechanical conditions to be studied.18 As the 

complexity of FEA models have increased, and more 

accurate material models and boundary conditions 

included, more confidence can be placed in these results. 

However, inherent limitations remain including the lack of 

material models that sufficiently accurately represent the 

biological materials of the residual limb. Furthermore, state 

of the art models demand significant computing resource 

and take a long time to set -up and complete making it 

currently unviable to conduct for large populations or in 

clinical settings.19  

Digital Image Correlation (DIC) and Digital Volume 

Correlation (DVC) have also been proposed as tools to 

investigate residual limb tissue strains. 3D-DIC was used to 

record residual limb surface deformation which could then 

be used to calculate gross tissue deformation.20 However, 

this can only be conducted while no socket is worn, and the 

position of internal structures cannot be recorded. Rankin et 

al. manufactured an analogue residual limb consisting of 

bone structures and an elastomer filled with sand particles 

to represent the soft tissues.21 DVC of the analogue residual 

limb, using Computer Tomography (CT) imaging, was then 

performed while wearing two socket types. The authors 

suggested that the clinical translatability of this method was 

poor and questions remain about how the sand particles 

affect the behavior of the elastomer, and how representative 

this composite is of biological tissue. 

Researchers have previously used the bone to skin surface 

distance when assessing body interfacing assistive 

technology designs in 2D22 and 3D.23-25 Changes in bone to 

skin distance infer the occurrence of tissue deformation. To 

the best of our knowledge, in the field of prosthetics, bone 

to skin distance in 3D has not been used as a tool to assess 

socket fit. 

This report details a methodology to calculate, present, and 

evaluate the distance between the internal bony surface 

and skin surface of a residual limb. Using this information, 

interface designs can then be compared. As a pilot study, 

this methodology is used to compare a hands-on Patellar 

Tendon Bearing (PTB) socket and hands-off pressure cast 

socket for a single transtibial prosthesis user using 

secondary Magnetic Resonance Imaging (MRI) data. 

METHODOLOGY 

From MRI data to 3D STL Models 

MRI images of one person with unilateral transtibial 

amputation were retrieved from a secondary dataset to use 

in this study (Figure 1).26 The MRI data used was randomly 

selected from 12 potential participants. All data had been 

previously anonymised, and hence ethical approval was not 

required. Two MRI datasets were used from the same 

participant; one of the participant’s residual limb while 

wearing a hands-on cast interface and one while wearing a 

hands-off cast interface. The MRI parameters used were as 

follows; field intensity 3 T, repetition time 6.9 s, time of echo 

1.5 s, inversion time 500 ms, Bandwidth 31.25 KHz, flip 

angle 12 deg, matrix 256 × 256, slice thickness 1.2 mm, 

voxel dimensions 1.17 × 1.17 × 0.6 mm, and a 1-signal 

average.26 The residual limb was fixed in position during the 

scanning procedure by placing the patellar in a knee-cap 

receptacle and harnessing the thigh using pads and 

strapping.  

The MRI data was imported into 3D slicer 5.2.2 medical 

image processing software.27 The following anatomical 

structures were segmented and extracted from the MRI 

datasets: 

•Soft Tissue                    •Meniscus and Patellar Tendon 

•Femur                            •Patella 

•Tibia                               •Fibula  

https://doi.org/10.33137/cpoj.v6i1.42196


 

3 

Arnstein T, Buis A. Methodology to investigate effect of prosthetic interface design on residual limb soft tissue deformation. Canadian Prosthetics & Orthotics 
Journal. 2023; Volume 6, Issue 1, No.7. https://doi.org/10.33137/cpoj.v6i1.42196 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X EFFECT OF PROSTHETIC INTERFACE DESIGN ON RESIDUAL LIMB SOFT TISSUE DEFORMATION  
Arnstein T, and Buis A, 2023 

 

Figure 1: MRI Image in coronal plane of participants residual limb 

showing femur, tibia, and soft tissues. 

Figure 2: STL model of participants residual limb. Hard tissue 

surface is shown in green. Skin surface is shown in orange. 

Segmentation was performed semi-automatically using the 

‘grow from seeds’ tool and then manually cleaned. The soft 

tissue segmentation included the skin, muscles, adipose, 

and connective tissues of the residual limb. The meniscus 

and patellar tendon were not included in the soft tissue 

structure as these are taken to be internal bodies that 

should be included in the hard tissue structure. The 

meniscus and patellar tendon were segmented together 

because of the challenge of processing individually. The 

other bony structures were segmented separately. Models 

were exported as stereolithography (STL) surface models.  

For each scan, the bone structures and meniscus/patellar 

tendon assembly were compiled into one STL file using 

Gmsh© model meshing software.28 This structure is hereby 

referred to as the hard tissue surface. This structure formed 

the surface for the nearest distance to the skin surface to be 

calculated from. The skin surface, being the outer surface 

of the soft tissue segmentation, was kept as a separate 

model (Figure 2).  

The internal bone surface model was trimmed 50mm 

proximally to the most distal point on the femoral condyles. 

This represented a distance more proximal than the most 

proximal point on the socket brim across both interface 

types, ensuring all tissue encapsulated by an interface was 

included. The trim command was repeated for the skin 

surface using the same trim plane with reference to the 

global coordinate system. 

CloudCompare software was used to calculate the 

distances between the STL vertices on paired surfaces 

using the nearest neighbour distance approach. For the first 

method of analysis, for each vertex on the internal bony 

surface, the corresponding nearest vertex on the skin 

surface is found and distance computed. For the second 

method of analysis, the hands-on and hands-off skin 

surfaces are registered and then distances between 

surfaces calculated. A description of each method is 

provided below: 

Internal bony surface to skin surface nearest distance; 

comparison between interface types. 

For each socket type, the distance from every vertex on the 

internal bony surface to the nearest vertex on the skin 

surface is computed. A histogram of the distribution of 

surface-to-surface distances is retrieved from 

CloudCompare with the nearest distances split into 100 

intervals. This process is repeated for both socket types. 

The number of nearest distance measurements for each 

socket type is then normalised to correct for discrepancies 

in the number of vertices of each STL file. The histogram for 

the hands-on and hands-off sockets are then combined into 

one graph. 

Hands-on interface vs. hands-off interface; skin surface 

visual comparison. 

Using Gmsh© software, a new STL file is created for both 

socket types that contains the skin surface and tibia surface 

only. These are loaded onto the CloudCompare interface. 

Next, the skin surface is separated from the tibia surface 

using the segment tool. Once complete, the tibia models are 

registered by aligning 10 manually selected equivalent point 

pairs. To ensure good registration, points are selected at 

key anatomical features that are easy to identify, and also 

at the extremities of the bone models. Finally, the tibia 

models are finely registered using CloudCompare’s inbuilt 

fine registration tool. The quality of registration is quantified 

by calculating the absolute and average Hausdorff 

https://doi.org/10.33137/cpoj.v6i1.42196


 

4 

Arnstein T, Buis A. Methodology to investigate effect of prosthetic interface design on residual limb soft tissue deformation. Canadian Prosthetics & Orthotics 
Journal. 2023; Volume 6, Issue 1, No.7. https://doi.org/10.33137/cpoj.v6i1.42196 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X EFFECT OF PROSTHETIC INTERFACE DESIGN ON RESIDUAL LIMB SOFT TISSUE DEFORMATION  
Arnstein T, and Buis A, 2023 

distances, a measure of similarity between shapes. The 

skin surfaces are then reinstated, and the nearest 

neighbour method is used to calculate the distance between 

both skin surfaces. The results are displayed as a heat map 

on the original skin surface. This process is then repeated 

with the other interface type as the reference surface and 

heat map inverted. The skin surfaces from both interface 

types are overlaid to allow the difference in surface topology 

to be visualised. 

RESULTS 

Internal bony surface to skin surface nearest distance; 

comparison between interface types (Figure 3). 

The nearest distance between the internal bony surface and 

skin surface, for every surface vertex, was calculated for 

both interface types: while wearing a hands-on interface 

and while wearing a hands-off interface. For the hands-on 

and hands-off interfaces, the maximum nearest distances 

between the internal hard tissue structure and skin surface 

were similar at around 60mm. The smallest nearest 

distances between the internal hard tissue structure and 

skin surfaces were in the order of 1mm for both sockets. For 

the hands-on socket, 4.4% of the skin surface was between 

7.8mm and 8.4mm from the internal bony surface, 

representing the most common distance for this condition. 

For the hands-off socket, 3.2% of the skin surface was 

between 9mm and 8.6mm from the internal hard tissue 

structure, representing the most common distance for this 

condition. When comparing the hands-on interface to the 

hands-off interface, the hands-on interface has a higher 

peak that is positioned further left along the x-axis. In 

contrast, the hands-off interface has a lower peak that is 

positioned further right along the x-axis. A greater 

proportion of the hands-off interface skin surface is found to 

be further away from the internal bony surface as seen at 

the right extremity of the x-axis (Figure 3).  

Hands-on interface vs. hands-off interface; skin surface 

visual comparison (Figure 4). 

After registration of the tibia models, the absolute 

bidirectional Hausdorff distance was 2.81mm and the 

average bidirectional Hausdorff distance was 0.43mm.  

The resulting skin surface geometries for the hands-on and 

hands-off interface types were compared. Areas highlighted 

in red show where the hands-on interface has a more 

compressive fit than the hands-off interface. Areas 

highlighted in blue show where the hands-off interface has 

a more compressive fit than the hands-on interface. The 

hands-on interface has a more compressive fit at the distal 

end of the residual limb, across the patellar tendon, above 

the medial and lateral femoral epicondyles. The hands-off 

interface has a more compressive fit more proximally on the 

residual limb, specifically on the anterior aspect. 

 

 

 

 

 

 

 

 

Figure 3: This graph shows percentages of the skin surface that 

are within a certain distance from the bone surface. The hands-off 

socket is shown in black/blue, and the hands-on socket is shown in 

gray/red. 

DISCUSSION 

The methods proposed in this report indicate deformation of 

residual limb soft tissues. The first method of analysis can 

be used to help understand how uniformly an interface 

design deforms residual limb soft tissue. The second 

method of analysis can be used to visualise where on the 

residual limb a socket design is more compressive and 

where the fit is more relaxed. This information can be used 

as a further tool to improve interface fit by providing a better 

understanding of how interface designs affect the soft 

tissues of the residual limb. 

Internal bony surface to skin surface nearest distance; 

comparison between interface types. 

The histogram profile is suggestive of interface fit. While 

wearing the hands-on interface, the higher peak of the 

histogram, positioned further left along the x-axis, points to 

higher levels of deformation, and hence strain, being 

induced in a larger volume of the residual limb than 

compared to the hands-off interface. In contrast, for the 

hands-off interface, the lower peak positioned further right 

along the x-axis suggests that this interface delivers a more 

uniformly compressive fit.  

A shorter distance between the internal bony surface and 

skin surface describes a smaller depth of soft tissue. At 

these smaller distances, less absolute deformation is 

required to induce higher, possibly dangerous, levels of 

tissue strain. There is a greater volume of residual limb in 

the first three intervals of the histogram (<1.8mm soft tissue 

depth) for the hands-on condition than for the hands-off 

condition. While a comparison to the no-socket condition 

cannot be made for this study, the more compressive fit over 

areas of shallow tissue depth for the hands-on condition 

indicates that high tissue strain levels will be generated.  

 

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Hands-on interface

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) 

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5 

Arnstein T, Buis A. Methodology to investigate effect of prosthetic interface design on residual limb soft tissue deformation. Canadian Prosthetics & Orthotics 
Journal. 2023; Volume 6, Issue 1, No.7. https://doi.org/10.33137/cpoj.v6i1.42196 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X EFFECT OF PROSTHETIC INTERFACE DESIGN ON RESIDUAL LIMB SOFT TISSUE DEFORMATION  
Arnstein T, and Buis A, 2023 

Hands-on interface vs. hands-off interface; skin surface 

visual comparison. 

Much of what is shown in Figure 4 agrees with hands-on and 

hands-off interface fit that has been reported in the 

literature. The classic features of the hands-on PTB socket, 

such as the patellar tendon bar, popliteal depression, and 

medial and lateral supracondylar depressions can be easily 

identified.29 The longer residual limb length while wearing 

the hands-off cast is also in agreement with previously 

reported literature.26 This suggests that the participants 

residual limb, and hands-on and hands-off casts, were fairly 

typical. Surprisingly there is no observable difference in 

socket geometry over the fibular head, a sensitive feature of 

the residual limb where offloading is commonly included as 

part of hands-on design.30 However, due to the small tissue 

depth over the fibular head, whether this methodology is 

sensitive enough to pick up any difference should be 

questioned. Interface pressure is commonly visualised 

using heatmaps31,32 but deformation or topology, as 

reported here, is less common with few examples.29 

Considerations and Future Work 

The nearest distance between the internal bony surface and 

skin surface, and skin surface to skin surface comparison 

between interface types, indicates deformation of residual 

limb soft tissues. However, the distribution of strain within 

residual limb tissues cannot be ascertained. Furthermore, 

whether a structure is at higher risk of tissue damage is not 

taken into consideration. Different tissues have different 

mechanical properties, discomfort or damage thresholds, 

and the makeup of different tissue types in an area of 

residual limb is not considered.18 There are also amputation 

specific factors that aren’t included such as the presence of 

scarring33 or an already compromised vascular system. 

The process of converting the MRI scans into STL models 

requires multiple steps, during which, some geometric 

accuracy is likely lost. This is especially pertinent when 

investigating structures with smaller soft tissue depths, 

nearing the resolution of the MRI data, where a loss in 

accuracy will have a big impact on the resulting error. High 

definition MRI data allows for more accurate segmentation. 

For future studies, what counts as sufficiently high-

resolution MRI data, must be defined. This should be noted 

as a significant limitation in this pilot study as the quality of 

the secondary MRI data was poor. 

During ambulation, prostheses are loaded dynamically and 

movement of the residual limb bones with respect to the 

socket wall occurs.34 The methodology presented in this 

report only looks at a static loading condition. Using this 

methodology to compare different levels of static loading 

while wearing the same interface would go some way to 

understanding how different interface designs influence 

residual limb soft tissue deformation during prostheses use.  

Comparing the geometry of the residual limb while wearing 

prosthetic devices against wearing no device would be of 

interest. Unfortunately, MRI images of the participant’s 

residual limb with no interface donned were not available for 

this study. Collecting MRI data of the residual limb without 

significant distortion of the tissues due to gravity is 

challenging. For this reason, imaging the residual limb while 

wearing only a liner to reduce sagging might be better suited 

as a baseline condition for comparison.  

This pilot study only reports on a single participant and 

therefore the results cannot be generalised to a wider 

 

 

 

Figure 4: Comparison of skin surface while wearing hands-on and hands-off interface using method 2. Areas where hands-on interface 

provides a more compressive fit when compared to the hands-off interface are shown in red. Areas where hands-off interface provides a more 

compressive fit when compared to the hands-on interface are shown in blue. 

 

Hands-Off 

Hands-On 

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6 

Arnstein T, Buis A. Methodology to investigate effect of prosthetic interface design on residual limb soft tissue deformation. Canadian Prosthetics & Orthotics 
Journal. 2023; Volume 6, Issue 1, No.7. https://doi.org/10.33137/cpoj.v6i1.42196 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X EFFECT OF PROSTHETIC INTERFACE DESIGN ON RESIDUAL LIMB SOFT TISSUE DEFORMATION  
Arnstein T, and Buis A, 2023 

population. Future work should focus on validating this 

methodology by comparing results to a range of other 

measures, for a larger study population to look for patterns 

in tissue deformation caused by interface fit, and including 

the liner-only condition. 

CONCLUSION 

The methodology presented in this report may give 

researchers a further tool to better understand how interface 

designs effect the soft tissues of the residual limb. When 

used to compare the residual limb of a single participant 

while wearing a hands-on and hands-off interface, 

differences in the distribution of nearest internal bony 

surface to skin surface distances were observed. A further 

study comparing interface designs to no prosthesis or liner 

only condition should be completed, upon which it will be 

possible to have more confidence in this technique. 

Attaining a complete understanding of the biomechanics of 

the residual limb and its interaction with prosthetic devices 

remains an unsolved challenge that limits the advancement 

of prosthetic interface design. 

ACKNOWLEDGEMENTS 

The authors would like to acknowledge 3D Slicer (www.slicer.org)27 

and Gmsh (https://gmsh.info/).28 The authors would also like to 

thank the EPSRC Centre for Doctoral Training in Prosthetics & 

Orthotics for its support. 

DECLARATION OF CONFLICTING INTERESTS 

The authors report that there are no conflicts of interest to declare. 

AUTHORS CONTRIBUTION 

Thomas Arnstein conceived the idea, conducted the research, 

and drafted the manuscript, while Arjan Buis provided supervision. 

Both authors actively participated in the discussion of results and 

contributed to the manuscript's revisions. 

 

SOURCES OF SUPPORT 

EPSRC GRANT NUMBER: EP/S02249X/1 

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