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Sarvesh Kutty
  1. Department of Neurosurgery, Leeds General Infirmary, Leeds, United Kingdom.

Correspondence Address:
Sarvesh Kutty, Department of Neurosurgery, Leeds General Infirmary, Leeds, United Kingdom.

DOI:10.25259/SNI_731_2022

Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Sarvesh Kutty. A summary of common grading systems used in neurosurgical practice. 28-Oct-2022;13:497

How to cite this URL: Sarvesh Kutty. A summary of common grading systems used in neurosurgical practice. 28-Oct-2022;13:497. Available from: https://surgicalneurologyint.com/surgicalint-articles/11957/

Date of Submission
13-Aug-2022

Date of Acceptance
12-Oct-2022

Date of Web Publication
28-Oct-2022

Abstract

Background: Grading and scoring systems are routinely used across various specialties in medicine and surgery. They help us assess the severity of disease and often guide management as well. In addition, grading systems allow us to prognosticate and gauge outcomes. Neurosurgeons also utilize an array of scores and grading systems. This article aims to collate some of the common grading systems used in neurosurgical practice to be utilized as an easy reference especially for junior doctors and other health-care providers working in this field.

Methods: An initial literature search was carried out to look at the grading systems in use. These were then distilled down to the ones that are frequently used in clinical neurosurgical practice based on my own experience as a doctor working in a tertiary neurosurgical unit. Neuro-oncology scoring systems were excluded from the study.

Results: Grading systems are grouped based on the area of neurosurgical practice they fall into such as cranial, vascular, spinal, and miscellaneous. A brief description of each grading system is provided and the conditions when they can be used in a tabular format. Discussion on the advantages and disadvantages of each grading system is not included in the study.

Conclusion: The list of grading systems in this article is not exhaustive. To the best of my knowledge, there seems to be no recent article, which summarizes them concisely. I hope that this summary will benefit the neurosurgical community and wider audience.

Keywords: Grading systems, Neurosurgery, Scores

INTRODUCTION

There are numerous grading systems used in neurosurgery. This article aims to give a brief summary of some of the commonly encountered grading systems in practice. For ease of use, tables are provided for each of them. Although there are various articles on the individual grading systems listed below, I believe that this concise tabular format will benefit clinicians working in neurosurgery. The grading systems have been classified into the subspecialty of neurosurgical practice they fall into. Neuro-oncology scoring systems were excluded from this study due to the complexity of the current guidelines.

CRANIAL NEUROSURGERY

Glasgow coma scale (GCS)

Professor Teasdale and Jennett first published the GCS in 1974 in the Lancet.[ 41 ] It is used worldwide not only in neurosurgery but also in many other fields of medicine to assess a patient’s conscious level and coma. Moreover, it serves as a practical tool for doctors and nurses to document neurological status regularly. The GCS has three components to assess; eye opening – which can be graded from 1 point to 4 points, verbal response from 1 point to 5 points, and motor responsiveness from 1 point to 6 points. The sum of each component is used to calculate an overall score. A minimum score is 3 and a maximum score is 15 [ Table 1 ]. In neurosurgical practice, the most important component is the motor score. When documenting GCS, it is helpful to document the individual breakdown for each component as well as the overall score, that is, E4, V5, M6, and GCS 15. If the patient is unable to verbalize, for example, due to endotracheal intubation or tracheostomy, then this should be specified when documenting the GCS. This is often abbreviated in the verbal score as V-T (for endotracheal tube or tracheostomy). Similarly, if the patient is dysphasic, then this is written as V-D.


Table 1:

Glasgow Coma Scale.

 

Pediatric GCS

The pediatric GCS [ Table 2 ] is slightly different to the adult version but assesses the same three components as above. This scale is used in children below the age of 2 years. Standard GCS scale can be used for those above the age of 2.[ 8 , 25 ]


Table 2:

Pediatric Glasgow Coma Scale.

 

Endoscopic third ventriculostomy (ETV) success score

An ETV is a procedure done mainly for obstructive hydrocephalus (noncommunicating). However, its use is not limited to this condition. The procedure involves making a hole in the floor of the third ventricle to allow cerebrospinal fluid to flow.[ 13 ] ETV success score was proposed by Kulkarni et al.[ 28 ] and was aimed to estimate the likelihood of ETV success at 6-month postoperatively. The score takes into account three components, namely, age of the patient; etiology; and history of a previous shunt and assigns percentage points based on this. The points are then added. A score >80% suggests a high likelihood of success, 50–70% suggests moderate likelihood of success, and <40% suggests a low likelihood of success[ 28 ] [ Table 3 ].


Table 3:

Endoscopic third ventriculostomy success score.

 

House-Brackmann classification for facial nerve palsy

This is a scoring system proposed by Dr. House and Brackmann in 1985. The purpose of this is to assess the severity of facial nerve palsy.[ 23 ] It consists of six grades, as shown in Table 4 . In neurosurgical procedures involving major vestibular schwannomas, avoidance of facial nerve injury is crucial. This grading system can be utilized to assess and track the patient’s facial nerve recovery.[ 40 ]


Table 4:

House-Brackmann classification for facial nerve palsy.

 

Frisen scale for papilledema

The Frisen and modified Frisen scale describes the grade of optic disk swelling in conditions with raised intracranial pressure.[ 17 ] These include conditions such as hydrocephalus and idiopathic intracranial hypertension.[ 15 ] It is particularly useful in both acute and chronic settings and is one of the indicators of severity of the above named conditions. It is also helpful in monitoring disease progression and treatment outcome[ 12 ] [ Table 5 ].


Table 5:

Frisen scale for papilledema.

 

Grading for diffuse axonal injury (DAI)

Adams et al. described in 1989 a grading system for DAI based on histology of anatomic distribution of cerebral hemorrhage.[ 2 ] There are three stages, 1–3, with worse outcome associated with higher grade. MRI classification proposed by Gentry[ 20 ] is shown in Table 6 .


Table 6:

MRI grading system for DAI.

 

The Glasgow outcome scale (GOS)

The GOS aims to assess outcome after head injury.[ 26 ] It consists of five grades. This may assist in assessing the patient’s requirements, such as rehabilitation needs post brain injury. An extended scale called the ‘GOS extended’ also exists. The GOS scale is shown in Table 7 .


Table 7:

Glasgow outcome scale.

 

VASCULAR NEUROSURGERY

Grading systems for subarachnoid hemorrhage (SAH)

There are three main grading systems used for aneurysmal SAH. The Hunt and Hess classification quantifies the severity of SAH to predict mortality.[ 24 ] It is based solely on clinical examination findings. The second grading system is the World Federation of Neurological Surgeons system, which is based on GCS and the presence or absence of neurologic deficits and aims to predict outcome based on this.[ 14 ] The third system is the Fisher grade and modified Fisher grade, which looks at the distribution and volume of blood on CT brain scan images and aims to predict the occurrence of cerebral vasospasm.[ 16 , 18 ] The three grading systems are highlighted in Table 8 .


Table 8:

Grading systems for aneurysmal SAH.

 

Spetzler-Martin grade for arteriovenous malformation (AVM)

The Spetzler-Martin grading system [ Table 9 ] aids in estimating the risk of surgical resection of cerebral AVMs.[ 38 ] This is based on three areas, eloquence of surrounding brain, presence of deep venous drainage, and the size of the nidus. Each area is given a score. The sum of the allocated points forms the grade. Higher grades (Grades 4 and 5) are generally unsuitable for surgical management.


Table 9:

Spetzler-Martin grade for arteriovenous malformation.

 

Alberta stroke program early CT score (ASPECTS)

The ASPECTS is a scoring system based on 10 points and is used to predict outcome of middle cerebral artery stroke.[ 6 ] A baseline score of 10 is assigned and points are deducted by 1 point for each of the following areas affected: caudate, putamen, internal capsule, and insular cortex, M1-M6 territories (1 point assigned to each of the M1-M6 territories). Lower scores are associated with worse outcome.

The intracerebral hemorrhage score (ICH)

The ICH score is used to help grade patients with ICH.[ 21 ] The scale takes into account the patients’ GCS, ICH volume, and intraventricular hemorrhage (IVH), whether or not the origin of the ICH is infratentorial and the age of the patient. Higher scores are associated with an increase in 30-day mortality. The score is graded 0–6 points. This is shown in Table 10 .


Table 10:

The ICH score.

 

Papile-Burstein classification for IVH

Another useful and commonly used grading system in neurosurgical patients is a grading system used for IVH proposed by Papile et al.[ 33 ] This is known as the PapileBurstein classification for IVH. It consists of four grades, with higher grades associated with a worse prognosis. It is based on CT scan findings. Table 11 shows this.


Table 11:

Papile-Burstein classification for IVH.

 

Classification systems for dural arteriovenous fistula (DAVF)

Borden et al. classification for DAVF was proposed in 1995.[ 7 ] It describes different types of DAVF which are grouped into three types. They are grouped based on their cortical venous drainage and their location. Types 2 and 3 tend to have a high risk of bleeding and causing problems such as neurologic deficit,[ 44 ] whereas Type 1 DAVF generally behave less aggressively.[ 39 ] The Cognard classification system was proposed in 2016 and has five grades and importantly takes into account the presence of venous ectasia and the direction of blood flow.[ 10 ] Both grading systems are depicted in Table 12 .


Table 12:

Classification systems for dural arteriovenous fistula.

 

NIH stroke scale/score (NIHSS)

The NIHSS aims to describe the severity of ischemic stroke, with a score of 0–42 being assigned to patients. Higher scores are associated with greater stroke severity.[ 29 ] It is also useful for predicting outcome after ischemic stroke. For every increase in 1 point, the likelihood of excellent outcome was decreased at 7 days by 24% and by 17% at 3 months.[ 1 ] A score of 1–4 is classified as a minor stroke and 5–15 is a moderate stroke. Scores above 21 are classified as a severe stroke. The scoring system is highlighted in Table 13 .


Table 13:

NIH stroke scale/score.

 

SPINAL NEUROSURGERY AND MISCELLANEOUS

American spinal injury association (ASIA) impairment scale and grade in spinal cord injury

This is a grading system consisting of five grades, allowing clinicians to assess the severity of spinal cord injury.[ 5 ] It also aids in determining rehabilitation requirements and potential for recovery/prognosis. It involves conducting a series of sensory and motor function tests based on a chart proposed by the ASIA.[ 4 ] After completing the chart, points are totaled. A maximum of 112 points can be given. The grading system is shown in Table 14 .[ 5 ] Complete ASIA spinal cord injury chart is not included in this article.


Table 14:

ASIA impairment scale for spinal cord injury.

 

Medical research council grading system for muscle strength

This is a commonly used grading system in neurosurgical practice to assess patient’s muscle strength. Much like the GCS, it serves as a reliable tool for nurses and doctors to utilize and regularly document the clinical status of the patient. In addition, it can guide treatment, assess response to treatment, and aid in prognostication. It consists of six grades (0–5), as depicted in Table 15 .[ 11 ]


Table 15:

Medical Research Council grading for muscle strength.

 

Karnofsky clinical performance status

The Karnofsky clinical performance status is useful in assessing patient’s functional status and suitability for treatment such as chemotherapy.[ 27 ] It also aids in determining prognosis and response to treatment, especially in chronic disease.[ 27 , 31 ] Patients are given a score between 0 and 100, 100 being the best possible score and 0 being the worst [ Table 16 ].


Table 16:

Karnofsky clinical performance status.

 

Modified Rankin scale

The modified Rankin scale is used to assess outcome after stroke. It is also useful to assess rehabilitation requirements[ 34 , 42 ] [ Table 17 ]. Over the years, the mRS has evolved as the primary outcome measure for nearly all acute stroke trials, even though it is considered as a single-item handicap scale. Neurosurgical diagnoses are complex and single-item scales might not be able to capture the depth of the clinical problem. Likewise, such scales are notorious for multiple and variable interpretations based on the person attempting the scoring in diverse settings. Appropriate statistical tests to analyze the scale results are important if study results using this scale are to be implemented in practice guidelines.[ 35 ]


Table 17:

Modified Rankin score.

 

Simpson grade of meningioma resection

The Simpson grade for meningioma resection aims to correlate the degree of surgical resection with the likelihood of meningioma recurrence.[ 32 , 37 ] There are also other factors, which play a role in determining risk of recurrence. Table 18 gives the grades of resection. The Simpson grade for meningioma was previously considered as the gold standard for defining the surgical extent of resection for the WHO Grade 1 meningioma.[ 9 ] The grade is based on intraoperative “eyeballing” of resection, which cannot be considered accurate. This has unearthed many controversies including rendering many previous outcome studies based on this grading system redundant. The technological advancements in the field of neurosurgery have diminished the value of this scale for prognostication of recurrence after meningioma resection. Many recent articles have urged to abandon this system in clinical practice but preserve its original message.[ 9 ]


Table 18:

Simpson grade of meningioma resection.

 

Anderson and D’Alonzo classification of odontoid process fracture

Anderson and D’Alonzo described an important and commonly used classification system for odontoid process fractures.[ 3 ] This classification is shown in Table 19 . There are three types of fractures, and this helps guide management of these fractures. Type 2 fractures have a higher a rate of nonunion and are usually unstable.[ 3 ]


Table 19:

Anderson and D’Alonzo classification of odontoid process fracture.

 

Galassi classification of arachnoid cyst

Galassi et al. described a classification system for middle cranial fossa arachnoid cysts in 1982.[ 19 ] It consists of three types of cysts based on radiological criteria. The classification is utilized to guide surgical management of these cysts. They are highlighted in Table 20 .


Table 20:

Galassi classification of arachnoid cyst.

 

DISCUSSION

There are a vast number of common and obscure grading systems in clinical and research practice. Sifting out the most relevant one for the clinical scenario is not an easy task for clinicians. Only by incorporating them into routine practice that one realizes that there is no single “gold standard” scale, rather many scales albeit with different properties. Based on your clinical requirement, one should choose the most appropriate grading system. The grading system should have the ability to be incorporated seamlessly into routine clinical use. Moreover, it should be reliable, repeatable, and provide a valid measurement for the specific outcome.

Over the past two decades, there has been an explosion of psychometric methods using statistical techniques in an attempt to provide strength to the measurements obtained from grading systems.[ 36 ] Measurements or scores obtained from scales are dependent on the scale itself as well as the subjects. These nonlinear variables can be transformed into interval measures, which give a more objective result, negating many problems such as underestimation.

Tremendous amount of work and expertise have gone into the creation of grading systems over the years and this article is an attempt to acknowledge these contributions to health measurements. In the process, I would like to draw the attention of clinicians to the nuances, limitations, and benefits of such systems, as pointed out by Massof[ 30 ] about two decades ago. The cardinal point to remember when we use these systems is to understand that “observations are always ordinal: measurements, however, must be interval” as aptly titled in their article by Wright and Linacre.[ 43 ]

CONCLUSION

Conclusions drawn from the various measurements used in grading systems dictate patient care. Some of them such as GCS scoring have immediate outcomes, whereas many disability ratings have significant long-term impact including health-care expenditure, clinical guidelines, and even policy-making. Therefore, it is crucial that those of us using them are aware of the validity and quality of the rating scales used in clinical settings. Many variables such as patient perspectives and quality of life indices studies do need stringent measurement criteria as they can change some clinical practices. These facts have been pointed out by studies of rating scales in the field of neurology, where the choice of rating scales had affected the clinical course of diseases such as multiple sclerosis.[ 22 ] Rigorous statistical analyses of the outcomes from grading systems are not a solution for the inherent issues with the scale itself. The above listed grading systems are some of the most commonly used in neurosurgical practice. As mentioned before, there are many other useful grading systems used in various areas of neurosurgery not included in this article. I hope that this summary will benefit the neurosurgical community and wider audience and serve as a handy reference tool.

Declaration of patient consent

Patient’s consent not required as there are no patients in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

References

1. Adams HP, Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR. Baseline NIH stroke scale score strongly predicts outcome after stroke: A report of the trial of org 10172 in acute stroke treatment (TOAST). Neurology. 1999. 53: 126-31

2. Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR. Diffuse axonal injury in head injury: Definition, diagnosis and grading. Histopathology. 1989. 15: 49-59

3. Anderson LD, D’Alonzo RT. Fractures of the odontoid process of the axis. J Bone Joint Surg Am. 1974. 56: 1663-74

4. ASIA and ISCoS International Standards Committ. The 2019 revision of the international standards for neurological classification of spinal cord injury (ISNCSCI)-what’s new?. Spinal Cord. 2019. 57: 815-7

5. Association American Spinal Inju, editors. Standards for Neurological Classification of Spinal Injury Patients. Chicago, IL: American Spinal Injury Association; 1982. p.

6. Barber PA, Demchuk AM, Zhang J, Buchan AM. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS study group. Alberta stroke programme early CT score. Lancet. 2000. 355: 1670-4

7. Borden JA, Wu JK, Shucart WA. A proposed classification for spinal and cranial dural arteriovenous fistulous malformations and implications for treatment. J Neurosurg. 1995. 82: 166-79

8. Borgialli DA, Mahajan P, Hoyle JD, Powell EC, Nadel FM, Tunik MG. Performance of the pediatric glasgow coma scale score in the evaluation of children with blunt head trauma. Acad Emerg Med. 2016. 23: 878-84

9. Chotai S, Schwartz TH. The simpson grading: Is it still valid?. Cancers (Basel). 2022. 14: 2007

10. Cognard C, Gobin YP, Pierot L, Bailly AL, Houdart E, Casasco A. Cerebral dural arteriovenous fistulas: Clinical and angiographic correlation with a revised classification of venous drainage. Radiology. 1995. 194: 671-80

11. Compston A. Aids to the investigation of peripheral nerve injuries. Medical research council: Nerve injuries research committee, His majesty’s stationery office: 1942; p. 48 (iii) and 74 figures and 7 diagrams; with aids to the examination of the peripheral nervous system. By michael O’brien for the guarantors of brain. Saunders Elsevier: 2010; pp. [8] 64 and 94 figures. Brain. 2010. 133: 2838-44

12. Das S, Montemurro N, Ashfaq M, Ghosh D, Sarker AC, Khan AH. Resolution of papilledema following ventriculoperitoneal shunt or endoscopic third ventriculostomy for obstructive hydrocephalus: A pilot study. Medicina (Kaunas). 2022. 58: 281

13. Demerdash A, Rocque BG, Johnston J, Rozzelle CJ, Yalcin B, Oskouian R. Endoscopic third ventriculostomy: A historical review. Br J Neurosurg. 2017. 31: 28-32

14. Drake CG, Hunt WE, Sano K, Kassell N, Teasdale G, Pertuiset B. Report of world federation of neurological surgeons committee on a universal subarachnoid haemorrhage grading scale. J Neurosurg. 1988. 68: 985-6

15. Dunn LT. Raised intracranial pressure. J Neurol Neurosurg Psychiatry. 2002. 73: i23-7

16. Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid haemorrhage visualized by computerized tomographic scanning. Neurosurgery. 1980. 6: 1-9

17. Frisén L. Swelling of the optic nerve head: A staging scheme. J Neurol Neurosurg Psychiatry. 1982. 45: 13-8

18. Frontera JA, Claassen J, Schmidt JM, Wartenberg KE, Temes R, Connolly ES. Prediction of symptomatic vasospasm after subarachnoid haemorrhage: The modified fisher scale. Neurosurgery. 2006. 59: 21-7

19. Galassi E, Tognetti F, Gaist G, Fagioli L, Frank F, Frank G. CT scan and metrizamide CT cisternography in arachnoid cysts of the middle cranial fossa: Classification and pathophysiological aspects. Surg Neurol. 1982. 17: 363-9

20. Gentry LR. Imaging of closed head injury. Radiology. 1994. 191: 1-17

21. Hemphill JC, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: A simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001. 32: 891-7

22. Hobart J. Rating scales for neurologists. J Neurol Neurosurg Psychiatry. 2003. 74: iv22-6

23. House JW, Brackmann DE. Facial nerve grading system. Otolaryngol Head Neck Surg. 1985. 93: 146-7

24. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg. 1968. 28: 14-20

25. James HE. Neurologic evaluation and support in the child with an acute brain insult. Pediatr Ann. 1986. 15: 16-22

26. Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet. 1975. 1: 480-4

27. Karnofsky DA, Burchenal JH, MacLeod CM, editors. The clinical evaluation of chemotherapeutic agents in cancer. Evaluation of Chemotherapeutic Agents. New York: Columbia University Press; 1949. p. 196-196

28. Kulkarni AV, Drake JM, Mallucci CL, Sgouros S, Roth J, Constantini S. Endoscopic third ventriculostomy in the treatment of childhood hydrocephalus. J Paediatr. 2009. 155: 254-9.e1

29. Lyden P, Brott T, Tilley B, Welch KM, Mascha EJ, Levine S. Improved reliability of the NIH stroke scale using video training. NINDS TPA stroke study group. Stroke. 1994. 25: 2220-6

30. Massof RW. The measurement of vision disability. Optom Vis Sci. 2002. 79: 516-52

31. O’Toole DM, Golden AM. Evaluating cancer patients for rehabilitation potential. West J Med. 1991. 155: 384-7

32. Oya S, Kawai K, Nakatomi H, Saito N. Significance of Simpson grading system in modern meningioma surgery: Integration of the grade with MIB-1 labeling index as a key to predict the recurrence of WHO Grade I meningiomas. J Neurosurg. 2012. 117: 121-8

33. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1,500 gm. J Pediatr. 1978. 92: 529-34

34. Quinn TJ, Dawson J, Walters M. Dr John Rankin; His life, legacy and the 50th anniversary of the Rankin stroke scale. Scott Med J. 2008. 53: 44-7

35. Quinn TJ, Dawson J, Walters MR, Lees KR. Reliability of the modified Rankin scale: A systematic review. Stroke. 2009. 40: 3393-5

36. Rasch G, editors. Probabilistic Models for Some Intelligence and Attainment Tests. Chicago: University of Chicago Press; 1960. p.

37. Simpson D. The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatr. 1957. 20: 22-39

38. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg. 1986. 65: 476-83

39. Strom RG, Botros JA, Refai D, Moran CJ, Cross DT, Chicoine MR. Cranial dural arteriovenous fistulae: Asymptomatic cortical venous drainage portends less aggressive clinical course. Neurosurgery. 2009. 64: 241-7

40. Sun MZ, Oh MC, Safaee M, Kaur G, Parsa AT. Neuroanatomical correlation of the House-Brackmann grading system in the microsurgical treatment of vestibular schwannoma. Neurosurg Focus. 2012. 33: E7

41. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974. 2: 81-4

42. Van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988. 19: 604-7

43. Wright BD, Linacre JM. Observations are always ordinal: Measurements, however, must be interval. Arch Phys Med Rehabil. 1989. 70: 857-60

44. Zipfel GJ, Shah MN, Refai D, Dacey RG, Derdeyn CP. Cranial dural arteriovenous fistulas: Modification of angiographic classification scales based on new natural history data. Neurosurg Focus. 2009. 26: E14

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