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71 (); 269-274
doi:
10.1016/j.jor.2025.08.050

Comparison of postoperative balance and function between primary and revision total knee arthroplasty

, ,
a Afyonkarahisar Health Sciences University, Faculty of Health Sciences, Physiotherapy and Rehabilitation, Afyonkarahisar, Turkey
b Dokuz Eylul University, Faculty of Physical Therapy and Rehabilitation, Orthopedic Physical Therapy, Turkey
c Dokuz Eylul University, Faculty of Medicine, Orthopedics and Traumatology, Turkey

⁎Corresponding author: Serpil Kalkan. serpil.kalkan@afsu.edu.tr

Received: , Accepted: ,
Professor P K Surendran Memorial Education Foundation
Disclaimer:
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Abstract

This study aimed to compare postural balance, functional performance, and patient-reported outcomes between primary total knee arthroplasty (pTKA) and revision total knee arthroplasty (rTKA) patients.

A cross-sectional analysis was conducted on 37 patients (57 knees: 30 pTKA, 27 rTKA) who were at least one-year post-surgery. Balance was evaluated using the Biodex Biosway system (postural stability, limits of stability, sensory interaction), while functional mobility was assessed with the 2-Minute Walk Test (2MWT), Timed Up and Go Test (TUGT), and 30-Second Chair Stand Test (30CST). Patient-reported outcomes included the Hospital for Special Surgery knee scale, Lower Extremity Functional Scale, Activities-specific Balance Confidence Scale, and SF-12 health survey. The Benjamini-Hochberg correction was applied for multiple comparisons.

The rTKA group was significantly older compared to the pTKA group (p < 0.01). The rTKA group demonstrated significantly worse postural stability with higher scores on the Anteroposterior Stability Index (p = 0.01) and Overall Stability Index (p = 0.007). In functional performance, the pTKA group significantly outperformed the rTKA group on the 2MWT (p = 0.003), TUGT (p = 0.03), and 30CST (p = 0.03). However, there were no significant differences in most patient-reported outcomes, except for a higher SF-12 Mental Component score in the rTKA group (p = 0.036).

rTKA patients exhibit significantly worse objective postural balance and functional performance compared to pTKA patients, despite achieving similar pain and functional scale scores. These findings, while influenced by the rTKA group's older age, highlight the need for tailored rehabilitation protocols that specifically address balance deficits and proprioception in this patient population.

Keywords

Total knee arthroplasty
Revision total knee arthroplasty
Balance
Functional outcomes
1

1 Introduction

Osteoarthritis (OA) is one of the most prevalent degenerative joint disorders worldwide, strongly associated with aging, obesity, and mechanical joint stress.1 Total knee arthroplasty (TKA) is widely recognized as an effective intervention to relieve pain and improve function and quality of life in individuals with end-stage OA.2,3 As the global population ages, the demand for surgical management of advanced knee OA has risen sharply. In the United States, the number of primary TKA (pTKA) procedures is projected to increase by more than 600 % by 2030, accompanied by a substantial rise in revision TKA (rTKA) procedures due to implant failure, increased patient longevity, and expanded surgical indications.3–5

While the pain-relieving and functional benefits of TKA are well documented, its effects on postural control and proprioception remain debated. Proprioceptive deficits are common in OA due to capsuloligamentous degeneration, and surgical intervention does not necessarily restore sensorimotor function.6 Some studies have reported improvements in balance and joint position sense after TKA with structured rehabilitation,7–9 whereas others have found no improvement or even deterioration in these parameters.10–12

These concerns are more pronounced in rTKA, where greater surgical complexity, prolonged recovery, and higher complication rates may further impair balance and mobility.13 Despite this, studies focusing on rTKA outcomes have primarily emphasized implant survival and complication rates, rather than neuromuscular performance or rehabilitation targets. There is a noticeable gap in the literature regarding comprehensive assessment of objective balance parameters and functional outcomes in rTKA patients, especially in comparison to primary TKA recipients.

Several studies have assessed balance or functional recovery after pTKA,14,15 and some have explored proprioception and fall risk in patients with knee OA.16 Despite this, no prior research has directly compared these two patient populations using an objective, instrument-based postural balance assessment. This highlights a significant gap in the literature, since the accurate quantification of postural control is crucial for assessing mobility limitations and fall risk in this patient population.

While some studies have compared pTKA and rTKA groups in terms of performance-based mobility tests, patient-reported functional outcomes, and quality of life, the results remain inconsistent.17–20 Certain investigations have reported clinically meaningful advantages favoring pTKA,17,18 whereas others have found no statistically significant differences between the two procedures.18–20 These conflicting findings highlight the need for a multidimensional assessment that integrates objective biomechanical measures with patient-reported perspectives to more accurately characterize postoperative recovery.

In the present study, we aimed to address this gap by conducting a comprehensive assessment of patients undergoing both pTKA and rTKA, incorporating instrumented postural balance testing with the Biodex Balance System, standardized functional performance measures, and validated patient-reported outcome instruments, including assessments of fear of falling and quality of life. This integrative approach provides a holistic understanding of recovery across physical and psychosocial domains and offers clinically relevant insights to inform rehabilitation strategies and guide postoperative expectations.

2

2 Method

2.1

2.1 Study design and participants

This descriptive, cross-sectional study was conducted between February and August 2017 at University hospital, Department of Physical Medicine and Rehabilitation and Orthopedics and Traumatology. Patients who had undergone pTKA or rTKA performed by a single orthopedic surgeon (VK) were identified from hospital records. To minimize variability in surgical expertise, operative techniques, and postoperative rehabilitation protocols, we selected patients treated by a single surgeon. While this approach limits the generalizability of our findings, it ensures greater consistency across both groups regarding factors that influence recovery and rehabilitation outcomes.

Sample size was calculated using G∗Power 3.1, based on a pilot study of 10 knees per group. The minimum required sample was 26 patients per group (effect size = 0.8, power = 80 %, α = 0.05). However, due to time constraints, the planned target number could not be reached. A subsequent post hoc power analysis indicated that the statistical power was limited to 63 %, which may increase the risk of a Type II error. This limitation has been noted in the discussion section.

Inclusion criteria were as follows: (1) undergoing pTKA or rTKA at least one year prior to assessment, (2) age≥40 years, and (3) regular follow-up at the study hospital. Exclusion criteria included: (1) cognitive or language barriers that impaired informed consent or instruction following, (2) moderate-to-severe knee pain at rest or during assessment (VAS≥50 mm), (3) comorbid conditions (orthopedic, neurological, systemic) interfering with balance or mobility, and (4) significant uncorrected vision or hearing impairments.

Despite the application of similar rehabilitation protocols to both groups, the progression of recovery in the postoperative period differed. The recovery process in rTKA patients did not show a linear trajectory; instead, it progressed more slowly than in the other group, making it more challenging to reach the targeted parameters. The inclusion criterion of having undergone surgery at least one-year prior was based on evidence that recovery in both populations progressively improves up to one year postoperatively, after which it plateaus with minimal further improvement.21–23

The study was approved by the Non-Interventional Research Ethics Committee of University, and all participants provided written informed consent.

2.2

2.2 Outcome measures

2.2.1

2.2.1 Demographics and clinical data

Demographic characteristics (age, gender, BMI, chronic disease, operated extremity, and follow-up time) were recorded. Pain levels before and after assessment were rated using the Visual Analog Scale (VAS). Participants also reported their exercise habits and history of falls.

2.2.2

2.2.2 Muscle strength

Quadriceps femoris and hamstring muscle strength were measured using a handheld dynamometer (Model 01163, Lafayette Instrument Company, USA). Strength measurements were performed on both limbs with standardized positioning.

2.2.3

2.2.3 Functional performance tests

Three validated performance-based assessments were used:

2-Minute Walk Test (2MWT): Participants walked back and forth along a 15-m corridor for 2 min. Assistive devices were allowed if needed. This test demonstrates good reliability in older adults and TKA populations.24

Timed Up and Go Test (TUGT): Participants stood up from a seated position, walked 3 m, turned, and sat back down. The test is a reliable indicator of mobility and fall risk.24,25

30-Second Chair Stand Test (30CST): Participants performed as many sit-to-stand repetitions as possible within 30 s. The test is recommended for assessing lower limb strength and predicting fall risk in older adults.26

All tests were standardized and demonstrated high test-retest reliability in TKA patients (ICC values of 0.97, 0.98, and 0.92, respectively).24,26

2.2.4

2.2.4 Patient-reported outcome measures

Hospital for Special Surgery (HSS) Knee Scale: Assesses pain, range of motion, and function. The Turkish version has demonstrated strong psychometric properties (ICC = 0.98).27

Lower Extremity Functional Scale (LEFS): A validated questionnaire to assess physical function in lower limb musculoskeletal conditions (Turkish ICC = 0.92).28

Activities-specific Balance Confidence (ABC) Scale: Measures confidence in performing balance-related activities. The Turkish version is validated in older adults and knee OA patients.29,30

Short Form-12 (SF-12): A widely used instrument for assessing health-related quality of life, encompassing both physical and mental health components. The Turkish version has demonstrated validity and reliability in musculoskeletal populations.31

2.2.5

2.2.5 Objective balance assessment

Balance was assessed using the Biodex Biosway Portable Balance System (Model 950-460, Biodex Medical Systems, USA), which includes:

Postural Stability (PS) Test: Measures the ability to maintain balance by assessing sway in anterior-posterior (A–P), medial-lateral (M–L), and overall directions. Lower values indicate better stability.

Limits of Stability (LOS) Test: Assesses the maximum distance a person can shift their center of gravity without losing balance. We used the “easy” difficulty level for all participants, as recommended for clinical populations.32

Modified Clinical Test of Sensory Interaction in Balance (mCTSIB): Assesses sensory contributions (vision, vestibular, somatosensory) to balance across four conditions.

The PS and LOS tests have demonstrated moderate to excellent intra- and inter-rater reliability (ICC range: 0.74–0.94) in older adults and clinical populations.33,34

2.3

2.3 Statistical analysis

All statistical analyses were conducted using SPSS v20.0 (IBM Corp, Armonk, NY). The significance level was set at p < 0.05. Due to the non-normal distribution of the data, Mann-Whitney U tests were used for group comparisons of continuous variables, while Chi-square tests were performed for categorical data.

For the Mann-Whitney U tests, the effect size (r) was calculated to measure the magnitude of the difference between groups. The r values were interpreted according to the widely accepted standards proposed by Cohen (1988): r = 0.10 indicates a small effect, r = 0.30 a medium effect, and r = 0.50 a large effect.

To control the Type I error rate resulting from multiple comparisons, the Benjamini-Hochberg correction was applied to all dependent variables. The corrected p-values are presented in the respective tables.

3

3 Results

3.1

3.1 Patient demographics and characteristics

A total of 153 patients registered under a single surgeon in the system were contacted (eight rTKA patients had passed away). However, some patients declined to attend follow-up visits, while others chose not to participate in the study. Data from two patients were excluded from the analysis after the X-ray assessment because one knee had a pTKA while the other had a rTKA. Thus, a total of 57 knees (30 pTKA and 27 rTKA) were analyzed.

Fifteen knees underwent rTKA after the initial surgery (pTKA with revision components), 11 knees underwent rTKA after the second surgery, and one knee underwent re-revision surgery. The surgeon's surgical technique for revision surgery was quadricepsplasty and quadriceps snip. rTKA was performed for six knees due to infection, six knees due to implant failure, four knees due to malalignment, seven knees due to ligament failure, and four knees due to insufficient bone stock.

The demographic characteristics of the patients showed no significant differences between the pTKA and rTKA groups for gender distribution (p = 0.11), operated extremity (p = 0.94), or postoperative exercise compliance (p = 0.23).

Analysis of patient demographics revealed significant differences in age and follow-up time. The mean age of patients in the rTKA group was significantly higher (71.00 ± 10.89 years) compared to the pTKA group (62.30 ± 8.56 years), a notable difference with a moderate effect size (p < 0.01, r = 0.42). Conversely, the pTKA group had a longer mean follow-up time (2.82 ± 0.62 years) than the rTKA group (2.27 ± 0.57 years), which was also statistically significant (p < 0.01, r = 0.46). All other variables -including height, weight, BMI, chronic diseases, postoperative falls, pain scores, and muscle strength-were comparable between the two groups (Table 1).

Table 1 Descriptive statistics of the groups (Continuous variables).
Variables pTKA rTKA p
Age 62,30 ± 8,56 71,00 ± 10,89 0,001 a
Height (m2) 1,60 ± 0,08 1,59 ± 0,07 0,80
Weight (kg) 84,50 ± 10,34 86,26 ± 19,69 0,58
BMI (kg/m2) 32,96 ± 3,27 33,02 ± 5,82 0,53
Follow-up time (year) 2,82 ± 0,62 2,27 ± 0,57 0,001 a
Number of chronic diseases 1,53 ± 1,04 1,56 ± 1,05 0.93
Number of falls (Postoperative) 0.43 ± 0,62 0,67 ± 1,51 0,54
Pain-Before assessment (VAS) 0,73 ± 1,6 0,52 ± 1,50 0,40
Pain-After assessment (VAS) 0,93 ± 1,7 0,52 ± 1,50 0,05
QF muscle strength (R) (kg) 14,73 ± 3,07 12,51 ± 4,30 0,07
QF muscle strength (L) (kg) 13,69 ± 2,94 12,44 ± 4,31 0,41
Hamstring muscle strength (R) (kg) 11,60 ± 4,41 10,93 ± 3,85 0,68
Hamstring muscle strength (L) (kg) 11,02 ± 3,79 12,14 ± 5,06 0,93
a p < 0.01, X: Mean, SD: Standard deviation, pTKA: Primary total knee arthroplasty, rTKA: Revision total knee arthroplasty, BMI: Body mass index, VAS: Visual Analog Scale, QF: Quadriceps Femoris.
3.2

3.2 Balance assessment

Balance assessment revealed significant differences between the groups, as detailed in Tables 2 and 3. The rTKA group demonstrated significantly worse postural stability, as indicated by higher scores on the Anteroposterior Stability Index (APSI) (adjusted p = 0.01) and the Overall Stability Index (OSI) (adjusted p = 0.007). Both of these findings were supported by a moderate effect size (r = 0.37). The Mediolateral Stability Index (MLSI) was also higher in the rTKA group, but the difference was not statistically significant. No significant differences were observed in LoS test score and duration or mCTSIB scores.

Table 2 Postural stability test.
Variables pTKA rTKA r p Adjusted p
APSI 0,98 ± 0,49 1,93 ± 1,41 0.37 0.005 b 0.01 a
MLSI 0,75 ± 0,47 1,29 ± 0,87 0.26 0.05 0.05
OSI 0,47 ± 0,30 1,07 ± 1,40 0.37 0.005 b 0.007 b
Table 3 Limit of stability test and modified clinical test of sensory interaction in balance.
Variables pTKA rTKA p Adjusted p
LoS Test Duration (seconds) 0,78 ± 0,46 1,03 ± 0,54 0.05 0.30
Total LoS score 37,07 ± 11,22 33,45 ± 10,74 0.33 0.49
SI score (Condition 1) 0,69 ± 0,28 0,83 ± 0,47 0.18 0.54
SI score (Condition 2) 0,97 ± 0,52 1,09 ± 0,56 0.46 0.55
SI score (Condition 3) 1,50 ± 0,59 1,71 ± 0,59 0.18 0.36
SI score (Condition 4) 2,96 ± 1,55 2,79 ± 0,95 0.54 0.54
3.3

3.3 Functional performance and patient-reported outcomes

In functional performance tests, the pTKA group consistently outperformed the rTKA group, as shown in Table 4. This was evidenced by a significantly greater distance covered in the 2MWT (adjusted p = 0.003), with a moderate effect size (r = 0.44). The pTKA group also performed significantly better on both the TUGT and the 30SCST (adjusted p = 0.03 for both), though these had a small effect size.

Table 4 Performance measurements.
Variables pTKA rTKA r p Adjusted p
2MWT (meters) 143,25 ± 42,57 102,70 ± 40,11 0.44 0,001 b 0.003 b
TUGT (seconds) 8,52 ± 1,46 10,13 ± 2,90 0.28 0,0 3 a 0 .03 a
30CST (number of repetition) 11,54 ± 2,32 10,04 ± 2,7 0.32 0,0 2 a 0.03 a

Regarding patient-reported outcomes, a notable difference was found in the SF-12 Mental component score, which was significantly higher in the rTKA group (adjusted p = 0.036) (Table 5). This finding, indicating better mental health in the rTKA group, had a moderate effect size (r = 0.36). No significant differences were found in the other patient-reported measures, including HSS scores, LEFS, ABC Scale, and the SF-12 Physical component score.

Table 5 Patient-reported outcome measurements and quality of life.
Variables pTKA rTKA p Adjusted p
HSS Knee Scale (R) 79,77 ± 9,18 76,33 ± 14,46 0.25 0.37
HSS Knee Scale (L) 79,03 ± 9,50 77,37 ± 14,76 0.82 0.82
LEFS 47,07 ± 11,89 47,56 ± 16,69 0.81 0.82
ABC Scale 77,64 ± 15,05 63,57 ± 25,69 0.05 0.15
SF-12 (Physical) 32,50 ± 9,73 36,16 ± 7,77 0.21 0.37
SF-12 (Mental) 33,06 ± 11,45 41,26 ± 8,09 0.006 b 0 .036 a
4

4 Discussion

The primary objective of this study was to conduct a comprehensive comparison of postural balance, functional performance, and patient-reported outcomes between patients who underwent pTKA and rTKA. To the best of our knowledge, this is the first study to use an objective, instrument-based assessment of postural control to directly compare these two patient populations. Our findings indicate that, despite achieving similar pain scores and muscle strength, rTKA patients exhibit significantly worse postural stability and functional performance compared to their pTKA counterparts.

A key finding of our study is the significantly worse postural stability in the rTKA group, as evidenced by higher scores on the APSI and OSI of the Biodex Balance System. This aligns with prior literature suggesting that proprioceptive deficits and altered neuromuscular control are more pronounced in rTKA patients due to greater surgical disruption of the joint capsule and surrounding tissues.9

The surgical complexity and anatomical changes associated with rTKA, such as potential bone loss and ligamentous instability, can further compromise the sensory information needed for effective postural control.13,35 While previous studies have shown mixed results regarding balance improvement after pTKA,6–9 and some have found no improvement or even deterioration,10–12 our direct comparison highlights a clear and substantial disparity in objective balance capabilities between the two groups.

It is crucial to note that no significant differences were found in the mCTSIB, suggesting that the rTKA group's balance deficit is not solely due to a specific sensory system (e.g., vision) but may be related to more complex sensorimotor integration issues.6–9 The high prevalence of balance disorders in the general elderly population further underscores the importance of this finding.36

The interpretation of these results, however, must consider the significant differences in age and follow-up time between the two groups, which act as potential confounding factors. The rTKA group was significantly older, and as advanced age is a known determinant of poorer balance, this demographic disparity likely contributes to the observed stability deficits.36,37 While both groups were assessed at least one year postoperatively, the rTKA group had a shorter mean follow-up period. This shorter duration may also play a role, as full recovery often follows a non-linear trajectory and the rTKA group may not have reached the same level of functional plateau as their pTKA counterparts, further complicating the direct comparison of balance outcomes.13,21–23

In terms of functional performance, our results show that the pTKA group consistently outperformed the rTKA group on all three tests: the 2MWT, TUGT and 30SCST. The significant difference in the 2MWT, with a moderate effect size, indicates a clinically meaningful difference in walking endurance and mobility.38 The poorer performance of rTKA patients on the TUGT and 30SCST, albeit with smaller effect sizes, further supports the conclusion that rTKA patients have greater limitations in dynamic balance, lower limb strength, and overall mobility.39–41 These findings are consistent with some prior research that has reported clinically meaningful advantages favoring pTKA in performance-based tests.18

However, these observed differences may have also been influenced by the confounding effects of age and follow-up time, which were not statistically controlled for in our analysis. Age is a well-established determinant of physical function, with older individuals consistently demonstrating poorer performance on mobility and strength tests like the TUGT, 2MWT and 30SCST.42–44

Patient-reported functional outcomes are controversial in the literature.17–20 In this study, no significant difference was found between the groups in parameters such as HSS, LEFS and ABC Scale. However, the rTKA group's significantly higher score on the SF-12 Mental Component score is noteworthy. This finding suggests that despite having poorer results on balance and mobility tests, the mental dimension of quality of life for rTKA patients is higher.

The higher SF-12 mental parameter may be consistent with studies on life satisfaction and general quality of life. For example, some research suggests that health-related quality of life is at its highest level in the 65–75 age range.45,46 This may partially explain the higher mental scores observed in our older rTKA group. While some studies show a decline in quality of life with advancing age, this relationship is not linear and unidirectional.47,48 However, age is not the sole determinant of health-related quality of life. Instead, it is a complex construct influenced by a multitude of factors, including gender, lifestyle, and individual beliefs. Thus, to support and improve health-related quality of life, a comprehensive assessment and a multidimensional approach are crucial.45,46 The fact that rTKA patients have gone through a longer and more complex surgical process13 may have increased their mental resilience and led them to appreciate even small improvements more.49 This finding once again emphasizes the complexity of recovery and the importance of a multidimensional assessment.37

4.1

4.1 Limitations and future directions

This study, while providing valuable insights, has several limitations that inform key directions for future research.

The most significant limitation of this study is its cross-sectional design, which prevents us from establishing causality or tracking the dynamic process of recovery over time. It is unclear if the observed deficits in the rTKA group are a result of the revision procedure itself or represent a persistent state from pre-existing conditions. To address this, future research should employ prospective or longitudinal designs to track how balance and function evolve in both patient populations and to determine if specific rehabilitation interventions could alter these trajectories.

A crucial methodological limitation was the lack of statistical controls for potential confounding factors. While we identified significant differences in age and follow-up time, our analysis did not include multivariate methods like multivariate regression or analysis of covariance to statistically account for their effects. Future studies must incorporate such analyses to more precisely determine the independent impact of the surgical procedure.

The single-surgeon, single-center design also restricts the generalizability of our findings. While this approach minimized variability in surgical technique and rehabilitation protocols, the specific revision techniques and implant choices may not be representative of broader clinical practice.50 To improve the external validity of these findings, future research should be conducted across multiple centers and involve diverse surgical approaches.

Our post hoc power analysis indicated that the study may have been underpowered to detect smaller, yet potentially clinically meaningful, differences. The low patient participation rate may have also introduced selection bias. Future research should aim for larger, multicenter cohorts to increase statistical power and mitigate this bias.

These limitations highlight several important avenues for future research and clinical practice. The clear deficits in postural stability and functional performance observed in rTKA patients suggest a need for more intensive, tailored rehabilitation strategies specifically targeted at improving balance and proprioception. The disconnect between the rTKA group's objective physical deficits and their higher self-reported mental health scores emphasizes the need to integrate both objective performance measures and subjective patient-reported outcomes to accurately assess recovery and screen for fall risk. Future studies could also explore the factors contributing to the higher mental health scores in rTKA patients and how this resilience can be leveraged to improve overall recovery.

5

5 Conclusion

This study provides a comprehensive comparison of patients who have undergone pTKA and rTKA, revealing significant differences in objective balance and functional performance. By utilizing an instrument-based postural stability assessment with the Biodex Balance System, we found that rTKA patients exhibited significantly worse postural control compared to their pTKA counterparts, as indicated by higher APSI and OSI scores.

In line with these balance deficits, the pTKA group consistently outperformed the rTKA group on all functional tests, including the 2MWT, TUGT, and 30CST. It is important to acknowledge that the rTKA group was significantly older and had a shorter mean follow-up time. These factors are well-known to influence balance and functional performance, and they may partially account for the observed disparities.

We found no significant differences in functional scales like the HSS or LEFS. However, the SF-12 Mental Component score was significantly higher in the rTKA group, a finding consistent with existing literature that highlights the complex relationship between age, health status, and quality of life.

These findings suggest that the clear physical deficits in the rTKA population underscore the need for specialized, intensive rehabilitation protocols that specifically target balance, proprioception, and dynamic stability. While the cross-sectional design and the confounding effects of age and follow-up time are limitations, this research sets the stage for future prospective studies to better track the recovery trajectory of these two distinct patient populations.

Author statement

Serpil Kalkan → Conceptualization, Methodology, Formal analysis, Investigation, Data Curation, Writing – Original Draft, Writing – Review & Editing, Visualization, Project Administration, Bayram Unver → Conceptualization, Methodology, Resources, Supervision, Project Administration, Vasfi Karatosun → Conceptualization, Methodology, Resources, Supervision.

Guardian patients consent

Written informed consent was obtained from all individual participants and/or their legal guardians involved in the study.

Ethical statement

Ethical approval for this study was obtained from the relevant ethics committee (Approval No. EK-7).

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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