Abstract
Objective:
This study aimed to investigate the relationship between spinopelvic parameters and radiographic foot axes and to examine whether these associations differ across age groups.
Methods:
This retrospective radiographic study analyzed imaging from patients treated at a university medical center for degenerative or traumatic conditions. Cases with weight-bearing, 2-view foot radiographs and standing lumbar spine radiographs, including the femoral heads, were included. Spinopelvic parameters (lumbar lordosis, pelvic tilt, sacral slope, and pelvic incidence) and radiographic foot axes (including hallux valgus angle, tibiotalar angle, and metatarsal declination angle) were measured, and correlation analyses were performed with age-based subgroup comparisons.
Results:
A total of 46 Caucasian patients (33 females, 13 males) were included (mean age 55.6 ± 18.5 years). Lumbar lordosis showed a significant negative correlation with hallux valgus angle (r = −0.29, P = .015). Sacral slope was negatively correlated with the hallux valgus angle (r = −0.42, P < .001). Pelvic tilt correlated positively with tibiotalar angle (r = 0.34, P = .004) and metatarsal declination angle (r = 0.25, P = .042). Age-stratified analyses demonstrated age-related differences in correlation patterns.
Conclusion:
Spinopelvic alignment demonstrates measurable associations with radiographic foot alignment, supporting the concept of the spine–pelvis–lower-limb unit as a biomechanically integrated system. Clinically, these findings suggest that integrated, chain-oriented assessment and management strategies (considering both spinal and foot alignment, particularly with aging) may be relevant when evaluating patients with coexisting spine and foot disorders.
Levels of Evidence:
Level IV, Prognostic Study.
Keywords: Axes, Correlation, Foot, Parameters, Pelvis, Relation, Spine
Highlights
Radiologic correlations between spinopelvic parameters and foot axes.
Age-related variations in correlation patterns across parameters.
Potential for targeted interventions in key anatomical regions.
Introduction
Modern medicine is increasingly specialized, and cross-disciplinary relationships are often insufficiently examined.1,2 In trauma and orthopedic surgery, spinal and foot surgeries are clearly separated; this may contribute to the lack of data on whether spinal axial alignment is associated with foot alignment and angles. Only a few studies have addressed the relationship between spinal pain or spinopelvic parameters and hallux valgus. Incel et al3 investigated the relationship between a hallux valgus deformity and lumbar lordosis in 20 patients with hallux valgus and 20 healthy controls. Their findings demonstrated a weak correlation between hallux valgus and hyperlordosis. Similarly, Hsu et al4 conducted a clinical study of 1000 patients with hallux valgus and 1000 patients without the condition. They identified an association between hallux valgus and complaints or deformities in the lumbar spine. Beyond these, no prior studies have addressed this topic; therefore, this is the first radiographic investigation to comprehensively correlate spinopelvic and foot parameters across age groups.
A clearer understanding of spinopelvic–foot interactions is clinically important, as changes in alignment within 1 segment of the axial–appendicular chain can provoke compensatory adjustments in others.5 Understanding these relationships may help refine clinical decision-making by enhancing preoperative planning in both spine and foot surgery, reducing postoperative imbalance and adjacent-joint overload, guiding the choice of treatment sequence (e.g., “spine first” versus “foot first”), and informing more targeted rehabilitation strategies.6
A comprehensive analytical investigation into whether there is a relationship between spinopelvic parameters and radiological foot axes has yet to be conducted. Such a relationship could have significant clinical implications. If associations between spinal and foot deformities can indeed be demonstrated, therapeutic approaches for 1 region may need to be evaluated for their effects on the other. This could potentially lead to novel treatment strategies, particularly in the realm of conservative therapies.
Materials and methods
Study cohort
In this radiographic study, the radiographic data of patients treated at a university medical center for degenerative or traumatic reasons from 2018 to 2024 were retrospectively analyzed. Datasets were required to include weight-bearing foot radiographs (unilateral or bilateral) obtained in 2 standard views (anteroposterior and lateral), as well as an upright, weight-bearing lateral lumbar spine radiograph that included the femoral head projection. The time interval between the spinal radiograph and the foot radiograph for the same patient could not exceed 2 years. The exclusion criteria were 1) idiopathic, congenital, neuromuscular scoliosis; and 2) advanced degenerative changes (spondylolisthesis > Meyerding Type 1), fractures, posttraumatic osteoarthritis, Charcot neuroarthropathy, and any tumors, metastases, infections, or other pathologies of the lumbar spine, pelvis, or foot skeleton that affected spinopelvic parameters or foot axes and angles of the patients (e.g., an undisplaced toe fracture would have been included). The study was approved by the Ethics Committee of the University Medical Center Göttingen (Approval No: 8/11/24 Date: 25 November 2024) . Patient-related data (age and sex) and reasons for presentation were recorded.
Spinopelvic parameters and foot axes
Spinopelvic parameters were measured radiographically as follows7: Lumbar lordosis (LL) as the angle between the superior endplates of L1 and S1, sacral slope (SS) as the angle between the S1 endplate and the horizontal reference line, pelvic tilt (PT) as the angle between the line from the femoral head center to the midpoint of S1 and the vertical reference line, and pelvic incidence (PI) as the angle between a line orthogonal to the S1 endplate and a line drawn from the midpoint of the superior endplate of S1 to the bicoxofemoral axis. Since PI is equal to the sum of SS and PT (PI = SS + PT), PI was calculated accordingly.7 Spinopelvic parameters depend on patient posture. For example, PT is greater in a relaxed, seated position than in a standing position, whereas SS decreases. In a deep-seated position with lumbar spine inclination, the values approximate those of standing.8,9 All imaging of the lumbar spine in this study was conducted in an upright standing position.
Foot axes were measured radiographically, in accordance with Lamm et al.10 The tibiotalar angle (TTA) is the angle between the tibial axis and the talar neck axis. The calcaneal inclination angle (CIA) is the angle between the weight-bearing surface and the plantar calcaneal line. The lateral Meary’s angle (LMA) is the angle between the talar neck axis and the first metatarsal axis. The metatarsal declination angle (MDA) is defined by the intersection of the weight-bearing surface and the first metatarsal axis. Navicular height (NH) is the vertical distance from the plantar medial navicular to the weight-bearing surface. To normalize NH (nNH), it was divided by the osseous foot length, which was measured as the distance between the vertical tangential lines drawn at the most posterior and most anterior osseous points of the foot. The hallux valgus angle (HVA) is formed by the intersection of a line bisecting the proximal phalanx of the hallux and another line bisecting the shaft of the first metatarsal (Figure 1).
Figure 1.
Measurements of spinopelvic parameters and foot axes. CIA, calcaneal inclination angle; HVA, hallux valgus angle; IMA, first intermetatarsal angle; LL, lumbar lordosis; LMA, lateral Meary’s angle; MDA, metatarsal declination angle; nNH, normalized navicular height; PI, pelvic incidence; PT, pelvic tilt; SS, sacral slope; TTA, tibiotalar angle.
When radiographs of both feet were available, left and right foot parameters were averaged to generate a single patient-level value. This approach was chosen to avoid violating the assumption of independence in the correlation analyses. All radiographic parameters were measured twice by a single investigator, with a 3-month interval between assessments. The radiograph assessor was not blinded to patient age. If there was more than a 20% difference between the 2 measurements, a third calculation was performed. In such cases, the 2 closest values were used for analysis. The final values were determined as the means of the 2 selected measurements. This process ensured high intrarater reliability, with a 2-way mixed intraclass correlation coefficient (ICC) > 0.9 indicating absolute agreement.11
Statistics
Data collection and organization were performed using Excel v16.16.25 (Microsoft, Redmond, WA, USA). Statistical analysis was conducted using GraphPad Prism 9.5.1 (GraphPad Software, San Diego, CA, USA). Data normality was assessed using the Shapiro–Wilk test prior to conducting parametric analyses. The Pearson correlation coefficient (r) was employed to assess the relationship between the spinopelvic parameters and foot axes. Correlation strength was categorized based on the r-value: 0.00-0.25 indicated no correlation, 0.25-0.50 represented a weak correlation, 0.50-0.75 denoted a strong correlation, and 0.75-1.00 signified a very strong or excellent correlation. Negative r-values reflected an inverse correlation. Statistical significance was defined as P < .05. A trend threshold of P < .1 was applied to reduce type 2 errors in this exploratory analysis, although it is acknowledged that such findings are not statistically significant and must be interpreted with caution. Subgroup correlations were not adjusted for multiple comparisons because the analysis was exploratory; strict correction would have increased type 2 errors and potentially obscured relevant associations. Data are displayed in terms of means and SDs.
Results
Cohort characteristics
A total of 46 Caucasian patients (33 females and 13 males) were included in the study. The overall mean age was 55.6 ± 18.5 years, with no significant age difference between the sexes ( P = .106). Reasons for presentation related to foot complaints were as follows: unspecified foot pain in 18 cases (39.1%), hallux valgus in 11 cases (23.9%), pes planovalgus in 9 cases (19.6%), osteoarthritis in 4 cases (8.7%), toe deformities in 3 cases (6.9%), persistent pain after ankle sprains in 2 cases (4.3%), metatarsalgia in 2 cases (4.3%), rheumatoid arthritis in 2 cases (4.3%), toe fracture in 1 case (2.2%), psoriatic arthritis in 1 case (2.2%), plantar fasciitis in 1 case (2.2%), and heel spur in 1 case (2.2%). For spine issues, the reasons for presentation were unspecified back pain in 28 cases (60.9%), degenerative scoliosis in 8 cases (17.4%), degenerative lumbar spine syndrome in 8 cases (17.4%), osteochondrosis in 6 cases (13.0%), spondylolisthesis Meyerding Type 1 in 4 cases (8.7%), spinal stenosis in 2 cases (4.3%), and follow-up after a fall onto the back in 2 cases (4.3%). X-rays were available for both feet in 23 patients, while only the right foot was examined in 12 patients, and only the left foot in 11 patients. The values for the spinopelvic parameters and foot axes are presented in Table 1.
Table 1.
Patient characteristics, spinopelvic parameters, and foot axes
| Parameter | Mean (±SD) | 95% CI |
|---|---|---|
| Age (years) | 53.8 (±19.8) | 49.0-58.4 |
| TTA | 62.8 (±8.9) | 60.7-64.9 |
| CIA | 20.1 (±7.1) | 18.4-21.8 |
| nNH (N) | 0.2 (±0.0) | 0.1-0.2 |
| LMA | −4.8 (±11.0) | −7.4 to 2.1 |
| MDA | 23.0 (±6.1) | 21.5-24.5 |
| IMA | 10.3 (±3.7) | 9.4-11.2 |
| HVA | 19.3 (±11.4) | 16.6-22.1 |
| LL | 54.8 (±17.3) | 50.7-58.7 |
| PT | 16.5 (±8.8) | 14.3-18.6 |
| SS | 37.6 (±11.3) | 34.9-40.4 |
| PI | 54.1 (±12.6) | 51.1-57.1 |
CIA, calcaneal inclination angle; HVA, hallux valgus angle; IMA, first intermetatarsal angle; LL, lumbar lordosis; LMA, lateral Meary’s angle; MDA, metatarsal declination angle; nNH, normalized navicular height; PI, pelvic incidence; PT, pelvic tilt; SS, sacral slope; TTA, tibiotalar angle.
Correlation analyses
Correlation analyses demonstrated weak but statistically significant negative associations between SS and HVA, and LL and HVA. Significant positive but weak correlations were observed between PT and TTA and between PT and MDA. In addition, significant correlations were found between PI and normalized navicular height and between PI and MDA. Figure 2 illustrates the associations between the spinopelvic parameters and foot axes.
Figure 2.
Overview of significant relationships between spinopelvic parameters and foot axes. Significant positive correlations were observed between PI and nNH, and PI and the MD, as well as between PT and TTA, and PT and the MD. Positive correlations are indicated by a “+” and negative correlations by a “−.”
Trends were observed for correlations between PT and LMA (positive), between PT and HVA (positive), between SS and IMA (negative), between PI and LMA (positive), between PI and IMA (negative), and between PI and HVA (negative).
With regard to the foot axes only, an excellent correlation was observed between MDA and LMA. Strong correlations were found between nNH and LMA and between nNH and MDA. Analysis of the spinopelvic parameters alone revealed a strong correlation between PI and SS. All correlations between foot and spine parameters are presented in Figure 3.
Figure 3.
Heat map of correlations. The upper italicized value in each heat map cell denotes the corresponding P-value, whereas the value displayed beneath it indicates the respective correlation coefficient (r). CIA, calcaneal inclination angle; HVA, hallux valgus angle; IMA, first intermetatarsal angle; LL, lumbar lordosis; LMA, lateral Meary’s angle; MDA, metatarsal declination angle; nNH, normalized navicular height; PI, pelvic incidence; PT, pelvic tilt; SS, sacral slope; TTA, tibiotalar angle.
To account for age-related changes, correlation analyses were conducted between age and spinopelvic parameters, as well as between age and foot axes. The results revealed a significant positive correlation between age and PT and a significant negative correlation between age and SS.
Furthermore, an analysis of the foot axes over time revealed that TTA, HVA, CIA, MDA, and LMA initially increased from early to middle age, followed by a slight decline. In older individuals, TTA, CIA, and HVA in particular exhibited a subsequent increase. Regarding spinopelvic parameters, LL decreased progressively over the lifespan, while SS demonstrated a gradual increase. Pelvic tilt remained stable until middle age, after which it declined in later years. Pelvic incidence, however, reached its peak during middle age (Figure 4).
Figure 4.
Foot axes and spinopelvic parameters for age groups. Changes in foot axes and spinopelvic parameters across different age groups are presented by third-order polynomial trendlines. CIA, calcaneal inclination angle; HVA, hallux valgus angle; IMA, first intermetatarsal angle; LL, lumbar lordosis; LMA, lateral Meary’s angle; MDA, metatarsal declination angle; nNH, normalized navicular height; PI, pelvic incidence; PT, pelvic tilt; SS, sacral slope; TTA, tibiotalar angle.
To account for age-related changes in the correlation analyses, the cohort was divided into 4 age-based subgroups using percentile ranges: the first group was 11-45 years (below the 25th percentile), the second group was 46-56 years (25th-50th percentile), the third group was 57-63 years (50th-75th percentile), and the fourth group was 64-88 years (above the 75th percentile). Age groups were defined using quartiles to ensure data-driven, equally sized subgroups and to avoid arbitrary age thresholds. This approach enhances statistical balance, reduces bias from uneven group sizes, and allows clearer assessment of age-related trends.12 Correlation analyses were then conducted separately for each subgroup (Figure 5).
Figure 5.
Heat maps of correlations by age group. The heat maps display the strength of correlations between parameters, with varying intensities of blue indicating the strength of positive correlations and varying intensities of red representing the strength of negative correlations. The upper italicized value in each heat map cell denotes the corresponding P-value, whereas the value displayed beneath it indicates the respective correlation coefficient (r). A: 11-45 years (first quartile); B: 46-56 years (second quartile); C: 57-63 years (third quartile); D: 64-88 years (fourth quartile). CIA, calcaneal inclination angle; HVA, hallux valgus angle; IMA, first intermetatarsal angle; LL, lumbar lordosis; LMA, lateral Meary’s angle; MDA, metatarsal declination angle; nNH, normalized navicular height; PI, pelvic incidence; PT, pelvic tilt; SS, sacral slope; TTA, tibiotalar angle.
The 4 groups exhibited distinct differences in the observed correlations. In the first group, a strong negative correlation was identified between LL and HVA. Significant strong positive correlations were observed between PT and TTA, PT and nNH, PT and LMA, PT and MDA, PI and nNH, and PI and LMA. In the second group, all significant correlations were negative. Among these, a significant excellent negative correlation was observed between PT and nNH. In addition, significant strong negative correlations were found between LL and nNH, PT and LMA, and PT and MDA. In the third group, all significant correlations were positive. Among these, significant strong correlations were observed between LL and IMA, PT and LMA, PT and MDA, SS and nNH, PI and nNH, and PI and MDA. In the fourth group, significant strong negative correlations were observed between LL and HVA, and SS and HVA. A significant strong positive correlation was identified between PT and HVA.
Discussion
Specializations in modern medicine may lead to insufficient exploration of the interrelationships between different systems.1,2 This has resulted in a knowledge gap regarding whether axial alignment of the spine is associated with foot axes. These findings demonstrate significant correlations between spinopelvic parameters and foot axes. Specifically, LL increased as HVA decreased, while PT rose with increasing TTA or MDA, and vice versa. Marked age-related variations in these relationships were also observed.
Incel et al3 conducted a radiographic comparison of 20 patients with hallux valgus and 20 healthy controls, focusing on spinopelvic parameters. They identified a significant difference in HVA between the 2 groups but found no statistical differences in the metatarsus primus varus angle, metatarsus omnis varus angle, IMA, second metatarsal angle, or hallux interphalangeal angle. These findings raise questions about the study cohorts or possibly the severity of the included hallux valgus deformities, as hallux valgus is typically analyzed using HVA, the distal metatarsal articular angle, and IMA.13 Notably, only HVA showed a weak correlation with coexisting hyperlordosis. This was contradicted by the findings of this study, which show a negative correlation between LL and HVA. It has been demonstrated that LL decreases with advancing age,14 while hallux valgus typically manifests in the later decades of life.15 These age-related changes led to the negative correlations observed in this study. From a clinical perspective, Hsu et al4 examined 1000 patients with hallux valgus and 1000 without the condition, identifying an association between hallux valgus and lumbar spine complaints or deformities. This finding aligns with the hypothesis that decreasing LL contributes to age-related issues, paralleling the progression of hallux valgus.
The analysis conducted in this study also revealed a negative correlation between SS and HVA. Similar to LL, the data indicated a decrease in SS with age, consistent with the findings reported by Mac-Thiong et al,16 who performed a radiographic analysis on 709 adults. A reduction in SS over time may account for its negative correlation with increasing HVA. Furthermore, positive correlations were identified between PT and TTA, as well as between PT and MDA. The data of the study showed an age-related increase in PT, which aligns with the current literature.16 An increasing PT, coupled with a decreasing LL, contributes to pelvic retroversion. This retroversion could alter the alignment of the lower limbs, potentially leading to increases in TTA and MDA. This aligns with Yazdani et al17 findings. Using biomechanical kinematic analysis, they demonstrated that hyperpronated feet result in anterior pelvic inclination. Pelvic incidence does not exhibit an age-related association,16 which may be attributed to its definition as the sum of SS and PT—2 parameters that exhibit opposing trends with age. Nevertheless, positive correlations were observed between PI and MDA, as well as between PI and the nNH. These relationships may be linked to changes in leg and foot axes resulting from age-related pelvic retroversion,16,17 while PI itself remains stable over time.
Subgroup analyses revealed nuanced age-related variations in correlation patterns across multiple parameters. Three prominent observations emerged from the current comprehensive investigation: 1) LL–HVA correlations showed a complex age dependency: a strong negative association in the first quartile weakened in the second quartile, shifted to a positive correlation in the third quartile, and returned to a negative correlation in the fourth quartile; 2) PT displayed similarly dynamic patterns, with strong positive correlations to nNH, LMA, and IMA in the first quartile, strong negative correlations in the second quartile, renewed positive correlations in the third quartile, and no significant associations in the fourth quartile; and 3) PI also demonstrated alternating trends, with positive correlations to nNH, LMA, and MDA in the first quartile, negative correlations in the second quartile, and positive correlations again in the third and fourth quartiles. These age-associated morphometric variations likely reflect complex biomechanical adaptations, potentially arising from muscular and skeletal developmental processes in early life stages and subsequent degenerative changes in later decades. As previously noted, LL decreases, and the pelvis undergoes retroversion with advancing age.16 In contrast, hyperpronation is associated with anterior pelvic inclination.17 It can therefore be hypothesized that increased pelvic retroversion results in supination of the foot, which may manifest as an increase in nNH, LMA, and MDA. However, the interpretative power of these findings is constrained by the limited sample size within each subgroup.
Regarding a kinematic approach of the spine–pelvis–lower-limb chain, age-related spinal changes, particularly disc degeneration, can reduce LL and flatten the lumbar spine, prompting compensatory pelvic retroversion to maintain global balance. This aligns with the findings of decreasing LL and decreasing PT with age. Pelvic retroversion itself further diminishes LL and shifts the center of gravity posteriorly over the femoral heads, altering femoral rotation and increasing the mechanical demand on the hip-stabilizing musculature.18-20 In parallel, the aging of the lower limbs involves diminished muscle power, particularly of the ankle plantar flexors. This may cause the lower limbs to interact with spinal malalignment. Synergistic internal femoral rotation arising from pelvic retroversion and foot hyperpronation can increase joint torque and modify load distribution across the hip, knee, and ankle.21,22 Consequently, lower-extremity compensation may include subtle chronic hip and knee flexion to keep the gravity line centered over the ankles. Consistent with this model, positive correlations between PT and TTA (knee flexion), as well as between PT and MDA (hyperpronation), were observed. Hyperpronation itself reflects collapse of the medial arch during weight-bearing23 and can heighten torque, alter ankle range of motion, and increase susceptibility to osteoarthritis, patellofemoral pain, or ligamentous injury.24,25 Interestingly, LL was not associated with hyperpronation or increased knee flexion in the present cohort but only with HVA; this concurs with findings by Duval, Lam, and Sanderson,26 who conducted a randomized controlled trial and found that experimentally induced foot pronation does not meaningfully increase LL. Therapeutically, evidence suggests that interventions should address the entire spine–pelvis–lower-limb chain, whether applied distally with effects extending upward27,28 or proximally with effects descending along the limb.29,30 The findings of this study support this integrative concept by demonstrating age-related associations between spinopelvic alignment and foot parameters. However, it must generally be considered that standing-only evaluation may overlook important functional changes, whereas combined standing and sitting imaging can help identify spinopelvic mobility abnormalities that may meaningfully influence surgical planning and outcomes (e.g., instability or dislocation risk).31
The foot axes measured in this study are largely consistent with the values reported in the literature.10 Minor deviations were observed for LMA, for which smaller values were recorded in this study. However, Lamm et al10 noted that radiographs in their study were obtained from a radiology department, without consideration of clinical indications or patient history. It is therefore possible that their cohort differs from ours, which exclusively includes patients treated for foot and back problems. Similarly, the spinopelvic parameters measured in this study align closely with the current literature.7 Nonetheless, LL was slightly lower and PT slightly higher compared to the values reported by Roussouly et al.7 A potential explanation for this discrepancy is that Roussouly et al7 focused exclusively on healthy participants, whereas this cohort included patients with clinical conditions.
This study has several limitations. First, the overall and subgroup sample sizes were small, largely because a combination of weight-bearing foot radiographs in 2 projections and lumbar spine imaging, including the femoral heads, is rarely available. Second, all participants were patients with foot or spine disorders, limiting the study’s generalizability to healthy populations. Third, hip–spine interactions and prior hip arthroplasty might have influenced spinopelvic parameters and their correlations with foot alignment; however, excluding these patients did not materially change the results. In addition, body mass index and lower-extremity alignment were not assessed and may represent further confounding factors. Finally, multiple subgroup analyses were performed without adjustment for multiplicity, increasing the risk of Type 1 errors; these results should therefore be considered exploratory.
Understanding spine–foot correlations may contribute to more comprehensive postural assessments and targeted rehabilitation strategies. While correlations between spinopelvic parameters and foot axes were weak in the overall cohort, subgroup analyses demonstrated pronounced age-dependent effects. Age-related changes, such as pelvic retroversion, may influence foot alignment, and vice versa. From a therapeutic standpoint, the results reinforce the rationale for chain-oriented therapeutic strategies that target the spine–pelvis–lower-limb unit as an interconnected system.
Funding Statement
The authors declared that this study has received no financial support.
Footnotes
Ethics Committee Approval: Ethics Committee of the University Medical Center Göttingen (Approval No: 8/11/24 Date: 25 November 2024).
Informed Consent: N/A
Peer-review: Externally peer-reviewed.
Acknowledgments: The authors would like to thank the University Medical Center Göttingenfor the institutional support contributed to data acquisition.
Author Contributions: Concept – F.E.R., F.K., K.J., M.P.M., H.S., W.L., R.P., P.J.R.; Design – F.E.R., F.K., K.J., M.P.M., H.S., W.L., R.P., P.J.R.; Supervision – F.E.R., F.K., K.J., M.P.M., H.S., W.L., R.P., P.J.R.; Resources – F.E.R., F.K., K.J., M.P.M., H.S., W.L., R.P., P.J.R.; Materials – F.E.R., F.K., K.J., M.P.M., H.S., W.L., R.P., P.J.R.; Data Collection and/or Processing – F.E.R., F.K., K.J., M.P.M., H.S., W.L., R.P., P.J.R.; Analysis and/or Interpretation – F.E.R., F.K., K.J., M.P.M., H.S., W.L., R.P., P.J.R.; Literature Search – F.E.R., F.K., K.J., M.P.M., H.S., W.L., R.P., P.J.R.; Writing Manuscript – F.E.R., F.K., K.J., M.P.M., H.S., W.L., R.P., P.J.R.; Critical Review – F.E.R., F.K., K.J., M.P.M., H.S., W.L., R.P., P.J.R.
Declaration of Interests: The authors have no conflict of interest to declare.
Data Availability Statement:
The data that support the findings of this study are available on request from the corresponding author.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author.

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