Вы находитесь на странице: 1из 12

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and

Home

January 22, 2013

Functional Electrical Stimulation Programs for People with SCI


Clinician and the Consumer Perspectives for Clinic and Home
APTA Combined Sections Meeting 2013 San Diego, CA January 22, 2013, 8:00-10:00am
Moderator: Jennifer French, MBA, Neurotech Network Speakers: !!Therese E. Johnston, PT, PhD, MBA, Jefferson School of Health Professions !!Candy Tefertiller, PT, DPT, ATP, NCS, Craig Hospital !!Lisa Lombardo, PT, MPT, Cleveland FES Center

Course Objectives
1.! Discuss the current evidence for the use of FES for people with SCI 2.! Discuss FES parameter applications and modifications to achieve optimal outcomes in individuals with neurologic disabilities 3.! Discuss the opportunities and challenges of implementing FES in the clinical setting. 4.! Understand multiple uses of FES from the perspectives of the consumer and clinician. 5.! Assess practical applications for successful implementation in the clinic and the home environment for FES 6.! Discuss lower cost alternatives to commercially available FES technologies and the financial implications of FES programs and technologies 7.! Explore current technology surrounding implantable FES systems and current functional applications for implantable FES systems

Course Agenda
! ! ! ! ! !

Priorities of Individuals with SCI

Introductions Parameters and Evidence for Common FES Applications: Therese Johnston Implementing a Clinical Program for FES: Candy Tefertiller Short Session Break Implantable FES Systems: Lisa Lombardo Consumer & Clinical Perspectives: Panel Question & Answer
Anderson, K.D. (2004) J. Neurotrauma, 21: 1371-1383.

Parameters used in Clinical FES FES Parameters and Evidence for FES in SCI
Therese E. Johnston, PT, PhD, MBA Thomas Jefferson University Philadelphia, PA ! Important to understand parameters
! To understand how units differ ! To make best decisions for the intervention

! Read the booklets that come with the equipment!

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and Home

January 22, 2013

Current (I)
! Rate of movement of charged particles in a conductor ! Involves transfer of energy that causes physiological change ! Directly related to the voltage ! Measured in amperes ! Our applications: milliamps (mA) ! On e-stim machines, often is the intensity dial

Resistance
! Defines the ease of ! Ohms Law I = V/R movement within V=IxR the conductor ! Measured in Ohms
! Therefore, as R increases, V needs to increase to maintain a constant I

Resistance in our Applications


! Use of gels, sponges, & wet gauze decrease the resistance ! Lotions, oils, dry skin, & callus increase resistance

Alternating Current
! Uninterrupted bidirectional flow of particles ! Polarity reverses as electrons move in one direction & then reverse

+ -

+ -

Pulsed Current
! Each pulse is an isolated electrical event

Pulse & Pulse duration


! Pulse = isolated electrical event ! Can be uni or bidirectional ! Pulse duration = time to complete one pulse ! Our applications: usually in microseconds (sec)
Pulse duration

+ -

+ -

+ -

+ -

Biphasic Pulsed Current

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and Home

January 22, 2013

Other Terms
! *Interpulse interval = time between pulses ! *Period = pulse duration + interpulse interval duration
Interpulse interval

*Frequency
! The number of pulses each second ! Important in fatigue
+ + + 1 sec 0 + + -

+ -

+ -

Period

+ -

This would represent 3 pulses per second (pps)

*Balance of Charge
! A waveform is balanced when: The area under the negative phase = the area under the positive phase
Balanced

Amplitude Characteristics
! Peak Amplitude ! Peak to peak amp
Peak amp Peak to peak amp

Unbalanced

! RMS amp: takes the shape of waveform into account. Is about 70% of peak amp for a true sinusoidal wave

This unbalanced waveform gives you a net positive charge for the pulse

*Ramp Up & Ramp Down Times


! Ramp Up: Time across successive pulses to reach peak amplitude (usually in seconds) ! Ramp Down: Returning to baseline
+ + + -

Clinical Stimulators
! Primary Parameters
! Pulse duration: usually less than 400 sec ! Amplitude: up to 100 mA ! Frequency: up to 100 pps

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

+ -

+ -

! These 3 parameters together are all important in how strong the electrical stimulus is & what effects it can create

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and Home

January 22, 2013

! Amplitude

Effects of Increasing Parameters

FES Applications
! This talk will include
! Walking ! Cycling

! Increases force production

! Pulse Duration
! Increases force production (& pain over 400sec)

! Frequency
! Increases firing rate ! Increases force ! Increases fatigue

FES as a Dorsiflexion Assist during Gait


! Electrodes are typically placed on the anterior tibialis and the peroneal nerve ! Triggered by a foot switch or external trigger ! Considered an orthotic substitute

Parameters from the Literature


! Pulse duration:
! 200-400 sec

! Frequency:
! To obtain tetany

! Amplitude:
! To create a 3- to 3+/5
(Diagram: Robinson, Snyder-Mackler pg 178)

! On/off time:
! Times with persons gait ! Need a control source

Possible Stimulators
! Portable stimulator that can use a trigger
! Foot/heel switch ! Hand trigger

Portable Stimulator
! Programmable parameters
! Pre-set ! Custom allows wide range

! Single application devices on the market


! WalkAid ! Bioness ! Odstock (UK only)

! Remote heel switch

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and Home

January 22, 2013

WalkAid
! One-channel stimulator ! Uses a Tilt or Heel Sensor to control stimulation ! Parameters
! 25-300 !sec ! 16.7- 33 pps ! Up to 200 mA ! Up to 3 sec on time (for exercise)

Bioness L300
! Gait Sensor
! In shoe and attached to shoe ! Detects speed & surface changes

! Parameters
! 200 !sec ! 30 pps ! 30-35 mA

Parastep Walking System


! Muscles stimulated by surface stim
! quadriceps, peroneal reflex for stepping, and the gluteal muscles

! Parameters: 24Hz, pulse width 150 !sec, & intensity up to 300mA ! The user can chose from
! sit/stand, stand/sit, right step & left step, and can increase or decrease the stim intensity while walking

Evidence for Walking with FES

Parastep, Sigmedics, Fairborn, OH

Parastep
! Series of 5 papers from Miami Project published on its effects (1997, Arch Phys Med Rehabil)
! 16 subjects, trained 32 sessions ! Outcomes
! ! ! ! ! ! " walking distance, standing duration, & pace " thigh and calf girth No change in BMD ! self-concept and " depression ! blood flow " time to fatigue, " workload, " VO2 during UE ergometry

FES: Incomplete SCI


! Field-Fote et al. 2011
! FES to peroneal nerve ! " walking speed & distance across groups (FES/OG, TM/manual A, TM/FES, TM/robotics) ! Distance " greatest in OG group who used FES

! Ladouceur et al. 2000


! FES for peroneal nerve (swing) & quadriceps (stance) ! With FES, saw ! " functional mobility ! " maximal overground walking speed

Papers by Guest et al., Jacobs et al., Klose et al., Nash et al, Needham-Shropshire et al.

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and Home

January 22, 2013

FES: Incomplete SCI


! Kim et al. 2004
! FES: surface peroneal nerve stimulator ! Results: Gait speed best with FES/hinged AFO combo, Best foot clearance with FES

FES Cycling

! Postans et al. 2004


! Acute SCI: FES to many muscles on TM ! Greater " in overground walking distance after FES and TM training ! No difference in walking speed gains

Parameters of FES Cycles


! Ergys
! 0-140 mA; 400-1000 !sec; 30, 40, 50, 60 pps

Common Intervention Times


! From the literature
! Most studies have subjects cycle for 30 mins 3x/week ! More recent studies have made changes to this
! Some increased duration to 1 hour ! Some increased frequency to 5x/week

! RT300
! 0-140mA, 100-1000 !sec, 10-100 pps

! Motomed/Hasomed
! 0-126 mA, 20-500 !sec, up to 180 pps (using doublets)

! In practice
! See 30-60 minutes 3-5x/week

Evidence for FES Cycling


! Bone
! Lauer et al. 2011 (peds): hip BMD ! more than in kids without SCI ! Lai et al. 2010 (acute): " loss of bone in distal femur ! Bloomfield et al., 1996: Bone ! only if cycling at >18W ! Chen et al. 2005: " in distal femur, proximal tibia ! Frotzler et al. 2008 (higher intensity): " in trabecular & total BMD and CSA in distal femoral epiphysis

Evidence for FES Cycling


! Muscle
! Demchak et al. 2005 (acute): less muscle loss ! Johnston et al., 2011 (peds): ! quadriceps volume & stimulated strength ! Scremin et al. 1999 (chronic): ! CSA of quadriceps, adductor magnus,!muscle to adipose ratio ! Duffell et al. 2008 (chronic): !stimulated quadriceps torque,!quadriceps fatigue resistance

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and Home

January 22, 2013

Evidence for FES Cycling


! Cardiorespiratory
! Hettinga, et al., 2008 (review): average VO2 increase of 1.05L/min (n=264) while cycling ! Johnston et al., 2011 (peds): " greater than kids with typical development ! Janssen et al., 2008 (chronic): Modified FES: ! VO2, HR, cardiac output, blood lactate ! Zgobar et al., 2008 (chronic): ! small artery compliance ! Berry et al., 2008 (chronic): ! peak power output, ! peak VO2

Conclusions
! Understand parameters needed and rationale for decision making ! Some evidence exists for the use of FES applications in SCI

Implementing a Clinical Program of Functional Electrical Stimulation


Candy Tefertiller, PT, DPT, ATP, NCS
Director of Physical Therapy at Craig Hospital

Intensive Activity Based Therapy


! Focus on recovery vs. compensation ! Retraining the neuromuscular system below the LOI for task execution ! Development and implementation of new technologies and interventions to facilitate repetition and task specificity ! Improvement in neuromuscular function seen even years after neurologic injury

FES Research
Electrical Stimulation and FES may offer an important avenue to facilitate movement in an injured musculoskeletal system and facilitate improved function via. **Neuroplasticity and/or **Improved Compensation
! ! ! ! ! ! ! ! ! ! Daly 2011: ! gait coordination; effects X 6 months Kesar 2011: ! AGRF, trailing limb angle, knee flexion (swing) Kesar 2010: !muscle performance with VFTs vs. CFTs Forssberg et al. 1977: phase dependent modulation Fung et al 1994: ! H-Reflex Perez et al 2003: " spasticity Bajd et al 1997: ! vertical swing Barbeau et al 2002: Therapeutic Effect Field-Fote et al 2005, 2011 (RCTs): ! OG speed Thompson 2012: SCI ! CST activity with 30 min PNS

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and Home

January 22, 2013

FES in the Clinic/Home


! Available Technologies:
! Foot Drop Systems
! Bioness L300 ! Walkaide

FES Cycling Classes:


! Inpatient and Wellness Classes
! 4-5 clients/hour ! 1PT; 1 Tech; 1-2 Volunteers ! Creates competitive and motivating environment ! Peer Support ! Transition to upright posture when appropriate

! Foot/Thigh Control
! Bioness L300 Plus

! FES Cycles
! Restorative Therapies (UE and LE cycles) ! Motomed (UE and LE cycles) ! Ergys

! FES Elliptical
! Restorative Therapies

ABT Program: Cycling #Elliptical

Neuroprosthetics
Nerve stimulation devices designed to replace or improve function of an impaired nervous system

Evaluate:
!Spasticity !Isolated Movement !Trunk Control

Transition:
!FES Bike#RT600 Commercially available for home and clinical use

FES in the Clinic:


! Combined with OG training
! ! ! ! ! ! ! ! Common Peroneal/TA Gastroc/soleus Hip flexors/extensors Trunk extensors Knee flexors/extensors Foot sensors reversed to control stance vs. swing phase Strength training (TA vs. Gastroc/soleus) for clonic activity Initiate stepping prior voluntary initiation

FES in the Clinic


! Developmental Sequencing ! Over ground training ! Core Strengthening

! Combined with developmental sequencing ! Combined with manually assisted BWS LTing

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and Home

January 22, 2013

FES Training Algorithm

FES in the Clinic

1.! 2.!

Assess unilaterally for all tasks As patient continues to progress, discharge FES unilaterally when standard is met.

AIS C and D, BI or CVA

Assess Over Ground Manual Treadmill

Over Ground Training

Manual Treadmill Training

Step Without assist

Step Requires assist

Step Requires Assist and/or Clonus in stance

Step without assist and no Clonus in stance Spasticity SCATS or MA unilateral

Spasticity SCATS or MA unilateral

FES

FES

! 1 on all 3 Synergy patterns Or ! 2 on MA

>1 on any Synergy patterns Or >2 on MA

! 1 on all 3 Synergy patterns Or ! 2 on MA

>1 on any Synergy pattern Or >2 on MA

No FES

FES

No FES

FES

FES and Locomotor Training


! Easily combined ! Manual Assist ! Over ground ! Reduces staff fatigue ! May reduce clonic activity ! May allow training at higher speeds including running ! Spinal Cord Assessment Tool for Spasticity (SCATS) ! Modified Ashworth

Conclusion Clinical Decision Making is the Key


! Lots of wonderful new technology in rehab to enhance our treatment plans ! They are simply the Tools.. we need to determine when, how and with whom to improve long term outcomes ! No one modality will work for everyone ! Use EBM to guide clinical decision making

Learning Objectives Implantable FES Systems


Applications of FES for SCI
! Discuss implanted FES research applications for spinal cord injury ! Provide benefits and limitations for each of the applications ! Discuss recommendations for the future

Lisa Lombardo, MPT


Cleveland FES Center

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and Home

January 22, 2013

Cleveland FES Center


Advancing Technology, Enhancing Life

Enabling technology
! Implanted StimulatorTelemeter (IST) Pacemaker for the body
! 12 - 16 stimulus channels ! up to 2 biosignal sensing (EMG) channels

Developing technology that improves the quality of life of individuals with disabilities through the use of Functional Electrical Stimulation and enabling the transfer of the technology into clinical deployment.
Functional Electrical Stimulation (FES) is the application of electrical stimulation to restore function. FES can be applied for therapeutic purposes or for replacement of lost function. Neural Prosthesis: A device that connects directly with the nervous system and uses FES to replace or supplement function.

www.FEScenter.org Email: Info@FEScenter.org

! Intramuscular electrode ! Multicontact spiral cuffs ! Universal External Control Unit (UECU)

Clinical Applications for SCI


! Trunk Control & Posture
! Pressure Sore Prevention ! Wheelchair Propulsion

FES Lower Extremity Research


! Inclusion
! ! ! ! ! ! ! ! C6-T12 SCI > 6 months post-injury Intact lower motor neurons Absence of psychiatric problems No untreated orthopaedic problems No acute medical problems Adequate social support Willingness to comply w/ followup procedures

! Exclusion
! ! ! ! ! ! ! Pacemaker Cardiac arrythmia Pregnancy Contractures Seizure disorder Obesity Untreated substance abuse ! Immunodeficiency ! Frequent UTIs ! Pressure sores

! Standing
! Transfers ! Balance

! Stepping

Trunk Control & Posture


Pressure Sore Prevention

Trunk Control & Posture


Wheelchair Propulsion

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

10

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and Home

January 22, 2013

Standing System
Transfer & Balance

Stepping System

Lower Extremity FES Summary


! Controlling posture and balance may be feasible and clinically relevant ! Implanted systems for standing after SCI are clinically viable ! Nerve cuffs can improve system performance ! Standing balance can be addressed in new ways ! FES with EMG control can enhance walking ability after incomplete SCI

Cleveland FES Center Programs


Spinal Cord Injury ! Hand Grasp ! Arm & Shoulder Movement ! Pressure Sore Prevention ! Trunk Control & Posture ! Restoration of Cough ! Urology/Pelvic Health ! Pain & Spasticity ! Standing & Transfer ! Walking Stroke ! Shoulder Pain Reduction ! Pain & Spasticity ! Mental Image/Upper Body ! Hand, Implanted System ! Hand, Functional Control ! Foot Drop ! Walking Stability ! Swallowing Assistance

Acknowledgements
Website: www.fescenter.org
Department of Veterans Affairs; Rehabilitation Research and Development Service National Institutes of Health: National Institute on Child Health and Human Development, National Center for Medical Rehabilitation Research, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and BioEngineering, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Deafness and Other Communication Disorders, National Institute on Disability and Rehabilitation Research U.S. Department of Education State of Ohio: Third Frontier Program Department of Defense: Army, Telemedicine and Advanced Technology Research Center (TATRC) Craig H. Neilsen Foundation, Davis Phinney Foundation, Lincy Foundation, Medtronic Foundation, Michael J. Fox Foundation, NDI Medical Inc, Case Western Reserve University, Cleveland Clinic Foundation, Paralyzed Veterans of America, SPR Therapeutics, Thomas Jefferson University, Wallace H. Coulter Foundation, Wiegand Family Foundation

Consumer & Clinician Perspectives Panel Question & Answer

ALL RESEARCH VOLUNTEERS & THEIR FAMILIES

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

11

Functional Electrical Stimulation Programs for People with SCI: Clinician and Consumer Perspectives for Clinic and Home

January 22, 2013

Considerations to Participating in any FES program


! Not all programs are appropriate for all populations ! Implanted vs. external ! Commitments of self, family/caregiver ! Time ! Out of pocket cost and/or reimbursement ! Potentially dangerous if not used properly use ! Peripheral nerve damage or skin damage ! Infections ! Over-stress or fatigue the stimulated muscles

Resources to Learn More for you and your clients


! Electrotherapeutic Terminology in Physical Therapy: APTA Section on Clinical Electrophysiology. Published in 2000. Available through the APTA on line store ! International Functional Electrical Stimulation Society Education Section. Website: http://www.ifess.org/cedu_consumereducation ! Neurotech Network Spinal Cord Injury Fact Sheet. Website: http://www.neurotechnetwork.org/educate_spinal_cord_injury.htm ! Also available on Spinal Cord Central: http://www.spinalcord.org ! Cleveland FES Center: http://www.fescenter.org

References
1.! Behrman AL, Harkema SJ. Physical rehabilitation as an agent for recovery after spinal cord injury. Phys Med Rehabil Clin N Am. May 2007;18(2):183-202, v. 2.! Beekhuizen KS, Field-Fote EC. Sensory stimulation augments the effects of massed practice training in persons with tetraplegia. Arch Phys Med Rehabil. Apr 2008;89(4):602-608. 3.! Hoffman JR, Ratamess NA, Cooper JJ, Kang J, Chilakos A, Faigenbaum AD. Comparison of loaded and unloaded jump squat training on strength/power performance in college football players. J Strength Cond Res. Nov 2005;19(4):810-815. 4.! Dobkin B, Apple D, Barbeau H, et al. Weight-supported treadmill vs over-ground training for walking after acute incomplete SCI. Neurology. Feb 28 2006;66(4):484-493. 5.! Field-Fote EC, Lindley SD, Sherman AL. Locomotor training approaches for individuals with spinal cord injury: a preliminary report of walking-related outcomes. J Neurol Phys Ther. Sep 2005;29(3):127-137. 6.! Lam T, Eng J, Wolfe D, Hsieh J, Whattaker M. A systematic review of the Efficacy of Gait Rehabilitation Strategies for spinal cord injury. Topics in Spinal Cord. Injury Rehabilitation: Apr 2007 13(1):32-57. 7.! Backus D, Tefertiller C. Incorporating manual and robotic locomotor training into clinical practice: Suggestions for Clinical Decision Making. Topics in Spinal Cord. Injury Rehabilitation: 2008 14(1):23-33. 8.! Benz EN, Hornby TG, Bode RK, Scheidt RA, Schmit BD. A physiologically based clinical measure for spastic reflexes in spinal cord injury. Arch Phys Med Rehabil. Jan 2005;86(1): 52-59.

References
9.! Barbeau H, Ladouceur M, Mirbagheri MM, Kearney RE. The effect of locomotor training combined with functional electrical stimulation in chronic spinal cord injured subjects: walking and reflex studies. Brain Res Brain Res Rev. Oct 2002;40(1-3):274-291. 10.! Fung J, Barbeau H. Effects of conditioning cutaneomuscular stimulation on the soleus Hreflex in normal and spastic paretic subjects during walking and standing. J Neurophysiol. Nov 1994;72(5):2090-2104. 11.! Perez M, Field-Fote C. Impaired posture-dependent modulation of disynaptic reciprocal Ia inhibition in individuals with incomplete spinal cord injury. Neuroscience Letters. 341 (2003): 225-228. 12.! Field-Fote EC. Electrical stimulation modifies spinal and cortical neural circuitry. Exerc Sport Sci Rev. Oct 2004;32(4):155-160. 13.! Musselman KE. Clinical significant testing in rehabilitation research: what, why and how? Phys Ther Rev. 2007; 12: 287-296 14.! Baily, SN, Hardin EC, Kobetic R, Boggs LM, Pinault G, Triolo, RJ. Neurotherapeutic and neuroprosthetic effects of implanted functional electrical stimulation for ambulation after incomplete spinal cord injury. J Rehabil Res Dev. 2010; 47(1): 7-16. PMD: 20437323 15.! Dutta A, Kobetic R, Triolo RJ. Gait initiation with electromyographically triggered electrical stimulation in people with partial paralysis. J Biomech Eng. 2009 Aug 131(8):081002. PubMed PMID: 19604014.

References
16.! Lambrecht JM, Audu ML, Triolo RJ, Kirsch RF. Musculoskeletal model of trunk and hips for development of seated-posture-control neuroprosthesis. J Rehabil Res Dev. 2009;46(4): 515-28. PubMed PMID: 19882486. 17.! Johnson T, G. Nemunaitis, J. Nagy, M. Boulet, L. Boggs, M. Miller, J. Anderson, H. Hoyen, M. Keith, K. Nicolackis, L. Murray, R. Triolo Trunk muscle neuromuscular stimulation: A case study of the effects on spinal alignment and respiratory function in a tetraplegic, American Spinal Injury Association (ASIA) meeting, June 19-22, 2008. 18.! Nataraj R, Audu ML, Kirsch RF, Triolo RJ. Comprehensive joint feedback control for standing by functional neuromuscular stimulation-a simulation study. IEEE Trans Neural Syst Rehabil Eng. 2010 Dec;18(6):646-57. Epub 2010 Oct 4. PMID: 20923741 19.! Triolo RJ, Boggs L, Miller ME, Nemunaitis G, Nagy J, Bailey SN. Implanted electrical stimulation of the trunk for seated postural stability and function after cervical spinal cord injury: a single case study. Arch Phys Med Rehabil. 2009 Feb;90(2):340-7. PubMed PMID: 19236990; PubMed Central PMCID: PMC2648134. 20.! Boninger M, French J, Abbas J, Nagy L, Ferguson-Pell M, Taylor SJ, Rodgers M, Saunders N, Peckham H, Marshall R, Sherwood A. Technology for mobility in SCI 10 years from now. Spinal Cord. 2012 Jan 17. doi 10.1038/SC. PubMed PMID: 22249329

Property of French, Johnston, Lombardo & Tefertiller, not to be copied without permission

12