|Year : 2012 | Volume
| Issue : 2 | Page : 83-90
Comparative study between Moss-Miami pedicle screw system and Hartshill rectangle for lumbar spondylolisthesis
Ajit Swamy1, Amit Swamy2, Vikram Jaisoliya1
1 Department of Orthopedics, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune, Maharashtra, India
2 MIMER Medical College, Talegaon, Pune, Maharashtra, India
|Date of Web Publication||3-Apr-2013|
Department of Orthopedics, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Many different treatment modalities have been advocated by different authors from time to time for lumbar spondylolisthesis. The principle underlying surgery includes stabilization of the slipping vertebrae. Various operative methods encompassing this principle include posterior interbody fusion, posterior stabilization, facet joint fusion, posterolateral fusion, excision of loose segment, and anterior interbody fusion. The objective of this study was to compare Moss-Miami pedicle screw system with Hartshill rectangle in the management of isthmic and degenerative lumbar spondylolisthesis.
Materials and Methods: A prospective study was carried out to compare clinical and radiological outcomes between Moss-Miami pedicle screw fixation with facet joint fusion and Hartshill rectangle fixation with facet joint fusion after adequate decompression for Isthmic and Degenerative Lumbar spondylolisthesis. All patients of spondylolisthesis as per inclusion criteria admitted undergoing decompression, posterior stabilization, and facet fusion during the period 2009-2011 in D.Y. Patil Medical College, Pimpri, Pune were included in the study.
Results: A total of twenty patients were included with mean age 47.15 years. Fifteen were females and five males. Seven females and three males underwent Moss-Miami pedicular fixation and eight females and two males underwent Hartshill fixation. Oswestry disability scoring (ODS) scores of the two groups was 4.25 and 4.23 respectively at the end of 12 months. Patients in both the groups improved significantly as assessed by the ODS system.
Conclusions: Our results show that both the Moss-Miami Pedicle screw fixation and Hartshill rectangle fixation were of similar benefit as regards the stabilization of the lumbar spine.
Keywords: Hartshill rectangle, pedicular screw fixation, spondylolisthesis
|How to cite this article:|
Swamy A, Swamy A, Jaisoliya V. Comparative study between Moss-Miami pedicle screw system and Hartshill rectangle for lumbar spondylolisthesis. Arch Int Surg 2012;2:83-90
|How to cite this URL:|
Swamy A, Swamy A, Jaisoliya V. Comparative study between Moss-Miami pedicle screw system and Hartshill rectangle for lumbar spondylolisthesis. Arch Int Surg [serial online] 2012 [cited 2021 Apr 15];2:83-90. Available from: https://www.archintsurg.org/text.asp?2012/2/2/83/110031
| Introduction|| |
Spondylolisthesis is one of the major structural changes in the spine, which occasionally gives rise to back pain. Although, the condition presents a dramatic X-ray picture it may remain asymptomatic. However, when the lesion itself is thought to produce symptoms the pathogenesis of symptoms must be established before embarking upon definitive treatment.
Many different treatment modalities have been advocated by different authors from time to time. These include steffi plates and screws, Harrington rod fixation, Luque rods, Hartshill rectangle, and sublaminar wiring. In many cases, the condition can be treated conservatively. However, when the symptoms persist, surgery needs to be performed. The principle underlying surgery includes stabilization of the slipping vertebrae. Various operative methods encompassing this principle include posterior interbody fusion, posterior stabilization, facet joint fusion, posterolateral fusion, excision of loose segment, anterior, and interbody fusion. ,,,
Interbody fusion techniques have been developed to provide solid fixation of spinal segments while maintaining load bearing capacity and proper disc height. The developmental evolution of posterior spinal segment instrumentation is derived from the pathologies of deformity correction and fracture fixation. ,,,
Surgery is not always necessary in spondylolisthesis, often an adequate course of spinal and abdominal rehabilitation, restriction of activities and other conservative measures will be sufficient. However, persistent pain in lower back, buttocks and thigh, sciatica or neurological deficit are sometimes severe enough to warrant fusion. There are many different fusion techniques and opinions vary as to the proper operation in spondylolisthesis. Posterior rather than anterior fusions are preferred by most because its technique is more flexible; it permits exploration of defects, nerve root and intervetebral discs.
In recent years, there has been increasing popularity in the use of implants, especially, Moss-Miami pedicle screw system in patients who undergo spinal fusion. Furthermore, there is a role of Hartshill rectangle providing good posterior stability. The main aim is to have rigid fixation to bony elements in the area and hopefully to improve fusion rates and eventual outcomes. No such similar study has been carried out previously and this was a pioneered study.
The purpose of the study is to compare the results between Moss-Miami Pedicle screw fixation group and Hartshill fixation group in terms of functional recovery of patients and clinical and radiological fusion and stability achieved.
| Materils and Methods|| |
Source of data
Twenty patients between the age groups of 20 years and 70 years with isthmic or degenerative spondylolisthesis underwent adequate trial (period of 6 month) of conservative management without significant relief of symptoms.
All patients of spondylolisthesis as per inclusion criteria were admitted for decompression, posterior stabilization, and facet fusion during the period 2009-2011 in D. Y. Patil Medical College, Pimpri, Pune were prospectively studied.
The patients were devided in to two groups. Group A included 10 patients undergoing decompression and Moss-Miami fixation with facet fusion and Group B included 10 patients undergoing decompression and Hartshill Rectangle fixation with facet fusion.
- Patient between age group 20 years and 70 years with symptomatic spondylolisthesis not relieved by conservative treatment.
- Spondylolisthesis between grade I and III (myerding classification). ,
- Only patients with Isthmic or degenerative spondylolisthesis were included.
- Patients with severe spondylolisthesis grade IV.
- Patients with associated scoliosis.
- Patients with failed previous lumbar surgery.
- American Association of Anesthesiologists grade 4 and above.
- Acute traumatic spondylolisthesis.
- Roentgenograms: Anteroposterior and standing lateral views of lumbo - sacral spine [Figure 1] were done. Furthermore, flexion extension views [Figure 2] of lumbo - sacral spine and oblique view to assess facet joint were recorded to note the instability.
The percentage of slip was measured as follow: 
% slip = ab × 100/ac
where ab is a line drawn from the L5 vertebra postero-inferior corner that is perpendicular to the S1 vertebra endplate; and ac =100.
Lumbar index represents the degree of trapezoidal deformity of the vertebra
Lumbar index = x/y × 100
Slip angle (α) is angular relationship between L5 and S1. This angle is formed by a line drawn perpendicular to the posterior aspect of first sacral body and a line drawn parallel to inferior aspect of fifth lumbar vertebral body. It is the best predictor of instability or progression of spondylolisthesis deformity.
- MRI - to evaluate site of nerve root compression, spinal canal diameters and status of disc and disc space height.
- Functional status of each patient was determined using Oswestry disability scoring system.
- Complete neurological evaluation of each patient in terms of root compression sign by straight leg raising sign (SLRT), sensation, power and reflexes.
After giving general anesthesia the patient is placed prone on a suitable spine frame or table with the hips in maximum extension, helping to maintain lumbar lordosis, this position affords partial reduction of an isthmic or degenerative spondylolisthesis, when present. The whole of the back is painted keeping the iliac crest exposed.
A standard midline approach is used; Internervous plane developed between paraspinal muscle; Paraspinal muscle is detached subpriostealy as a unit from bone using dissector to expose spinous processes, the facet joints, and lamina both side.
Moss-Miami pedicle screw fixation
The C-arm is angled until the round cortical margins of the pedicle are clear and true A.P image is seen. The tip of the burr is positioned in the center of the pedicle, at the junction of the pars interarticularis and the transverse process, and a starting point is made with the burr. A 3.2 mm drill bit is aligned down the axis of the pedicle using fluoroscopy so that a "bulls-eye" image is obtained. The drill bit orientation is maintained while the C-arm is brought to a lateral and under direct fluoroscopic vision, the drill bit is advanced into the pedicle with a mallet. After an approximate depth of 15 millimeters is reached, a retractor in the wound is used to maintain a reference for the orientation of the pedicle, and the drill bit is removed. Using this reference guide for orientation, the pedicle is tapped for the appropriate size screw, using periodic lateral fluoroscopic images to confirm positioning. An instrument, such as a depth gauge, is used to probe for bone in all four quadrants of pedicle. The pedicle screw (MOSS-MIAMI SYSTEM) is inserted at the appropriate level and these steps are repeated for the remaining three pedicles. The rod is contour to match the natural lordosis. Rod is engaged between multi axial screwhead and cut 0.5-1 cm. longer. After securing the rod and inserting locking screw distraction applied and locking screw tighten [Figure 3]. Hemostasis achieved throughout procedure. The dura is covered with an autologous fat graft and gel foam and the wound is closed over suction drain.
Hartshill rectangle fixation
Once the midline posterior exposure was complete lateral up to the transverse processes, the sublaminar spaces are created by cutting the interspinous ligaments and midline ligamentum flavum. This is a key step. Once the sublaminar spaces are exposed in the entire levels to be instrumented, 20 gauge stainless steel double looped wires are passed at each level (in caudal to cephalad direction). The size of loop rectangle required is then measured and adequately contoured. Wires are tied onto the loop rectangle with cephalad wire ends inside the loop rectangle and caudal wire ends outside the loop rectangle [Figure 4].Post-operative X-rays are shown in [Figure 5] and [Figure 6].
Post-operatively the I.V. antibiotics are continued for 5 days followed by oral antibiotics for a period of 10 days. Regular wound check is done with the drain being removed on 2 nd post-operative day and the sutures removed an average of 13 days.
Physical therapy post surgery starts immediately. Ankle toe movements and deep breathing exercises started on the same day to prevent circulatory and respiratory complications.
By the 1 st day post-surgery patient is turn to side and active lower limb movements started with care to keep hip flexion <90°. Recruitment of core muscles pelvic floor muscles and adductors also form an important part of rehab in first few days. If pain persists beyond 5 days, soft-tissue mobilization or modalities like Interferential therapy are started.
The patient is propped up starting at 30° on the 2 nd day and bed side sitting is achieved with brace on by day 4 or 5. Walking is started on the same day as bed side sitting if patient is comfortable. Once patient starts walking exercises to improve balance and proprioception are started.
Neural tissue mobilization is started by the end of 1 st week if radiating pain persists. Patient is discharged between 8 th and 10 th day post-operative with the home program. Brace is to be continued for 3 months post-operatively. Once brace is discontinued dynamic exercises for the trunk and gym ball exercises are started.
If patient has neurodeficit, rehabilitation will depend on pattern of weakness of the muscles and orthotic support may be required.
Patients were assessed radiographically and clinically pre-operatively and at 3, 6, and 12 month post-operatively.
Clinical and functional outcome were measured with the ODS system applied on each individual patient and by SLRT. Furthermore, the complication rates were recorded.
Fusion and stability outcomes were assessed radiographically using AP and lateral and oblique radiographs. Lateral standing flexion-extension films were obtained beginning in 3 months.
Fusion was judged based on following criteria
- Solid fusion across both facet joints
- Partial fusion across one and solid fusion across other facet joints
- Partial fusion across both facet joints
- No fusion
Statistical analysis was carried out by GraphpadInstat-3 software.
| Results|| |
This prospective study included 20 patients, mean patient age 47.15 years. Mean patient age in group A was 47.2 years and in group B 47.1 years [Table 1], P value (>0.05) there were total 15 Female (75%) and 5 Male (25%). Group A included 7 Female (35%) and 3 Male (15%), group B included 8 Female (40%) and 2 Male (10%) [Table 2]. P value (>0.05) according to Fisher's Exact test.
Eight patients had neurological involvement. Others were operated due to progressively worsening backache. P value (>0.05) according to Fisher's Exact Test. In 13 (65%) patients spondylolisthesis located at spinal level L5-S1 [Table 3]. Majority of the patients (65%) had degenerative spondylolisthesis [Table 4].
No. of patients as per the grade of spondylolisthesis
Nine patients had grade I spondylolisthesis (45%) while nine patients had grade II spondylolisthesis (45%) and two patients had grade III spondylolisthesis (10%). In group A, five patients had grade I spondylolisthesis (25%) while four patients had grade II Spondylolisthesis (20%) and one patient had grade III spondylolisthesis (5%). In group B, four patients had grade I spondylolisthesis (20%) while five patients had grade II spondylolisthesis (25%) and one patient had grade III spondylolisthesis (5%). P value (>0.05) according to Mann Whiteny test.
The functional improvement to the patients is shown in [Table 5]. No significance difference between two groups.Further, all included patients were satisfied with the outcome of the surgery. Straight leg raising test was carried out to check nerve root stretching, which was free bilaterally at the end of 12-month duration in both groups.Mean duration of surgery in group A was 247 min and in group B it was 202.1 min.
Radiological evaluation at most recent follow-up
Lumbar radiographs with anteroposterior, lateral and lateral standing flexion-extension films and oblique view were obtained beginning with the 3 rd month, 6 th month, 12 th month, and when available, the 24 th month films also, as stability checked.
The fusion status was judged based on the criteria listed before, an evaluation done by an independent observer not included in the study.
All the patients included in the study showed satisfactory bony fusion as judged by solid fusion at both facet joint. Radiological fusion was seen earliest on 3 rd month check X-ray. None of them showed movement on the flexion and extension views.
One patient had superficial skin infection. However, it did not require any further operative procedure and got healed on its own following local wound care. No other complications were observed.
| Discussion|| |
The ideal surgical treatment for spondylolisthesis patients remains controversial. Moller  reported a prospective randomized study with 111 patients with isthmic spondylolisthesis and with a follow-up of 2 years. Patients were submitted to conservative treatment or a postero-lateral surgical approach with or without placement of pedicle screws. They concluded that surgery provided better clinical outcome and pain improvement.
Gibson  published a meta-analysis comparing the various methods of treatment of lumbar spondylolisthesis. The study concluded that there was no evidence that surgical decompression or fusion were superior superior to the natural history, placebo, or conservative management.
Apel  found high rates of pseudoarthrosis (43%) in patients submitted to a simple posterior fusion procedure, without good clinical outcomes. Herkowitz and Kurz  studied prospectively 50 patients with degenerative spondylolisthesis that were equally divided into two groups. Patients were submitted to isolated surgical decompression or decompression with postero-lateral fusion. Follow-up period was 3 years. Patients submitted to decompression and fusion presented better results than decompression alone (96% vs. 44%). Pseudoarthrosis rate in the decompression alone group was 36%, but it had no influence in clinical results.
Fishgrund  published a prospective randomized study with three different groups of patients with degenerative spondylolisthesis, submitted to different surgeries; Decompressive laminectomy, fusion without instrumentation, and fusion with instrumentation. Patients submitted to fusion and the instrumentation presented better fusion rate, but it did not improve the clinical outcome.
Kornblum  reviewed the study of Herkovitz and Kurtz and followed the patients for 7 years. They found the pseudoarthrosis rate influenced the final results. In patient with solid fusion, 86% presented good or excellent results, and the patients with pseudoarthrodis had only 56% of good or excellent results. The authors recommend then the use of instrumentation with pedicle screws in patients submitted to fusion.
Yuan,  in a multi-centric study with 2684 patients lumbar spondylolisthesis, compared 2177 patients submitted to fusion with pedicle screws with 507 patients submitted to decompression without pedicle screws. The complications of both procedures were analyzed. They noted 1% screw fracture. Per-operative dural tears were present in 7.3% patients in the pedicle screws group, and in 5.7% in the decompression without fusion group. CSF fistula was found in 0.5% in the fusion group, and in 0.7% in the decompression group. Re-operation rate was 17.6%, and 15%, respectively, for the fusion with pedicle screw group, and decompression alone group. They conclude the benefits of pedicle screws over its risks.
Madan  compared 23 patients with lumbar spondylolisthesis submitted to a posterior fusion procedure with 21 patients submitted to a posterior fusion procedure and interbody fixation. Three patients in the first group lost surgical correction of the spondylolisthesis, while no patient in the second group presented such complication.
However, the overall complication rate was not statistically significant between the two groups. Some authors consider the PLIF procedure difficult due to the increased bleeding, prolonged operation time, and more extensive dissection. , The reported complications associated with the PLIF procedure include: permanent neurological deficit in 0.4-1.7%; CSF leak in 0.4-0.5%; radicular pain in 1.1-2,5%; posterior displacement of the cage in 0.8-0.9%; deep wound infection in 0.6-5.0%. Suk  compared two groups of patients with lumbar spondylolisthesis. Group I comprised 40 patients submitted to decompression and fusion with pedicle screws. Group II comprised 31 patients submitted to decompression, postero-lateral fusion, and a PLIF with the placement of discal space grafts. The pseudoarthrosis rate in group I was 7.5% with 20% recurrence of deformity and lost of reduction in more than 50% of the cases. They recommend the posterior fusion associated with interbody grafting (PLIF), since anterior support presents lost of reduction achieved in surgery.
Schnee et al. studied outcome analysis for 52 adults with spondylolisthesis treated with posterolateral fusion and transpedicular screw fixation in 1997 and concluded that autologous posterolateral arthrodesis combined with pedicle screw fixation resulted in a high fusion rate, and contributed to successful outcomes in the treatment of certain subgroups of adults with spondylolisthesis.
Booth et al. assessed 36 patients with degenerative spondylolisthesis with a minimum follow-up of 5 years following treatment with decompression, autogenous bone grafting, and instrumented posterior fusion. Eighty-three percent of patients were extremely or somewhat satisfied with the results of surgery after a follow-up period of 5-14 years.
In our study, degenerative spondylolisthesis patients were more common (65%) than isthmic (35%) and both were more common in female patients. Grade 1/2/3 spondylolisthesis patients were 25%/20%/5% in group A whereas in group B it was 20%/25%/5%, which shows that grade 1 more common in group A and grade 2 in group B, but statistically not significant.
The literature shows concerns with life quality in spondylolisthesis patients. Madan  used the Oswestry questionnaire, among other tools, to evaluate the final outcomes of patients with lumbar spondylolisthesis submitted to a posterior fusion procedure.
Oswestry index of 69% was reported in the posterior fusion group, and an 81% index was reported in the PLIF group. PLIF patients retained correction and presented better fusion.
Our study shows marked improvement in Oswestry Disability score post-operatively with good to excellent results in both groups patients with improvement of SLR, which shows that both procedures are equally good.
Mean duration of surgery in group A was 247 min and in group B 202.1 min, which is not statistically significant. However, technique wise Hartshill fixation procedure is easier to carry out than Moss-Miami pedicle screw fixation, which requires good image control because of this time surgery took less time in Hartshill group than MossMiami group.
We achieved good solid radiological fusion earliest on 3 rd month check X-ray in both groups with good stability checked on flexon-extension X-ray.
One patient in group B got superficial skin infection, which got healed on regular dressing. No other complications related to biomechanics were noticed.
| Conclusion|| |
- Based on the present series, we conclude that if there is spondylolisthesis with or without instability and nerve root compression symptoms, decompression with the Facet joint fusions with instrumentation by Moss-Miami pedicle screws or Hartshill rectangle provide a solid mechanical construct and solid fusion.
- Both surgical procedures are effective, when functional recovery and duration of surgery were considered.
- Technically, Hartshill fixation procedure is easier to carry out than Moss-Miami pedicle screw fixation, which require good image control, because of this time duration was less in Hartshill group compared to Moss-Miami group.
- There were no complications noticed related to spinal biomechanics in both groups. Clinical and functional outcome in both groups were similar, no significant statistical difference found, however, all patients were satisfied with the both procedure.
- This preliminary study of 20 patients shows that Spinal decompression and facet joint fusion with posterior instrumentation (Moss-Miami pedicle screw, Hartshill) appears to be a safe and effective procedure, provides good solid fusion and biomechanic construction in a symptomatic stable or unstable spondylolisthetic patients.
| References|| |
|1.||Kumar A, Kozak JA, Doherty BJ, Dickson JH. Interspace distraction and graft subsidence after anterior lumbar fusion with femoral strut allograft. Spine (Phila Pa 1976) 1993;18:2393-400. |
|2.||Zlotolow DA, Vaccaro AR, Salamon ML, Albert TJ. The role of human bone morphogenetic proteins in spinal fusion. J Am Acad Orthop Surg 2000;8:3-9. |
|3.||Zucherman JF, Zdeblick TA, Bailey SA, Mahvi D, Hsu KY, Kohrs D. Instrumented laparoscopic spinal fusion. Preliminary Results. Spine (Phila Pa 1976) 1995;20:2029-34. |
|4.||Alden TD, Pittman DD, Beres EJ, Hankins GR, Kallmes DF, Wisotsky BM, et al. Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy. J Neurosurg 1999;90:109-14. |
|5.||Bridwell KH, O'Brien MF, Lenke LG, Baldus C, Blanke K. Posterior spinal fusion supplemented with only allograft bone in paralytic scoliosis. Does it work? Spine (Phila Pa 1976) 1994;19:2658-66. |
|6.||Esses SI, Natout N, Kip P. Posterior interbody arthrodesis with a fibular strut graft in spondylolisthesis. J Bone Joint Surg Am 1995;77:172-6. |
|7.||Fujimaki A, Crock HV, Bedbrook GM. The results of 150 anterior lumbar interbody fusion operations performed by two surgeons in Australia. Clin Orthop Relat Res 1982;165:164-7. |
|8.||Grob D, Scheier HJ, Dvorak J, Siegrist H, Rubeli M, Joller R. Circumferential fusion of the lumbar and lumbosacral spine. Arch Orthop Trauma Surg 1991;111:20-5. |
|9.||Meyerding HW. Spondylolisthesis. Surg Gynecol Obstet 1932;54:371-379. |
|10.||Beadon K, Johnston JD, Siggers K, Itshayek E, Cripton PA. A repeatable ex vivo model of spondylolysis and spondylolisthesis. Spine (Phila Pa 1976) 2008;33:2387-93. |
|11.||Bourassa-Moreau E, Mac-Thiong JM, Labelle H. Redefining the technique for the radiologic measurement of slip in spondylolisthesis. Spine (Phila Pa 1976) 2010;35:1401-5. |
|12.||Möller H, Hedlund R. Surgery versus conservative management in adult isthmic spondylolisthesis - A prospective randomized study: Part 1. Spine (Phila Pa 1976) 2000;25:1711-5. |
|13.||Gibson JNA, Waddell G, Grant IC. Surgery for degenerative lumbar spondylosis (Cochrane Review). In: The Cochrane Library Issue 2002;1:1-24. |
|14.||Apel DM, Lorenz MA, Zindrick MR. Symptomatic spondylolisthesis in adults: Four decades later. Spine (Phila Pa 1976) 1989;14:345-8. |
|15.||Herkowitz HN, Kurz LT. Degenerative lumbar spondylolisthesis with spinal stenosis A prospective study comparing decompression with decompression and intertransverse process arthrodesis. J Bone Joint Surg Am 1991;73:802-8. |
|16.||Fischgrund JS, Mackay M, Herkowitz HN, Brower R, Montgomery DM, Kurz LT. 1997 Volvo Award winner in clinical studies. Degenerative lumbar spondylolisthesis with spinal stenosis: A prospective, randomized study comparing decompressive laminectomy and arthrodesis with and without spinal instrumentation. Spine (Phila Pa 1976) 1997;22:2807-12. |
|17.||Kornblum MB, Fischgrund JS, Herkowitz HN, Abraham DA, Berkower DL, Ditkoff JS. Degenerative lumbar spondylolisthesis with spinal stenosis: A prospective long-term study comparing fusion and pseudarthrosis. Spine (Phila Pa 1976) 2004;29:726-33. |
|18.||Yuan HA, Garfin SR, Dickman CA, Mardjetko SM. A Historical cohort study of pedicle screw fixation in thoracic, lumbar, and sacral spinal fusions. Spine (Phila Pa 1976) 1994;19:2279S-96. |
|19.||Madan S, Boeree NR. Outcome of posterior lumbar interbody fusion versus posterolateral fusion for spondylolytic spondylolisthesis. Spine (Phila Pa 1976) 2002;27:1536-42. |
|20.||Suk SI, Lee CK, Kim WJ, Lee JH, Cho KJ, Kim HG. Adding posterior lumbar interbody fusion to pedicle screw fixation and posterolateral fusion after decompression in spondylolytic spondylolisthesis. Spine (Phila Pa 1976) 1997;22:210-9. |
|21.||Booth KC, Bridwell KH, Eisenberg BA, Baldus CR, Lenke LG. Minimum 5-year results of degenerative spondylolisthesis treated with decompression and instrumented posterior fusion. Spine (Phila Pa 1976) 1999;24:1721-7. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]