Caring for Wounded Warriors with Vision
and Hearing Impairment
Overview of the Vision Research Program
Robert Read, MBA
CDMRP Program Manager
April 17, 2015
Congressionally Directed Medical
Research Programs (CDMRP)
DEPARTMENT
OF DEFENSE
DEPARTMENT
OF THE ARMY
ARMY
MEDICAL
COMMAND
MEDICAL
RESEARCH
AND
MATERIEL
COMMAND
CONGRESSIONALLY
DIRECTED MEDICAL
RESEARCH PROGRAMS
Congressionally Directed Medical
Research Programs (CDMRP)
The CDMRP…
● Targets research as directed by Congress
● Employs a flexible science management model to accommodate rapid change
● Recruits and integrates consumer participation at all levels
● Uses an Institute of Medicine-recommended two tier review for technical merit
and mission relevance
● Supports the Office of the Assistant Secretary of Defense Health Affairs
(OASD[HA]), Defense Health Program (DHP), Defense Medical Research and
Development Program (DMRDP)
Since 1992, the CDMRP has…
● Administered over $8.7 billion in congressional
appropriations
● Processed more than 80,000 applications
● Provided over 12,400 grants to institutions world-wide
● Focused efforts on over 30 different research programs
U.S. Army Medical Research and Materiel Command
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Congressionally Directed Medical
Research Programs (CDMRP)
• Unique public/private
partnership
encompassing the
military, scientists,
disease survivors,
advocates, consumers,
and policy makers
• Support execution and
management of DHP
military medical
research
• Fund high-impact,
innovative medical
research to find cures,
reduce the incidence
of disease and injury,
improve survival, and
enhance the quality of
life for those affected
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Defense Medical R&D*
Peer Reviewed Orthopedic
Reconstructive Transplant*
Orthotics/Prosthetics Outcomes
Alcohol and Substance Abuse
Psychological Health/Traumatic Brain Injury*
Breast Cancer
Prostate Cancer
• Joint Warfighter*
Peer Reviewed Cancer
• Military Burn
Tuberous Sclerosis Complex
• Spinal Cord Injury
Amyotrophic Lateral Sclerosis
• Gulf War Illness
Bone Marrow Failure
• Vision
Peer Reviewed Medical
• Ovarian Cancer
Duchenne Muscular Dystrophy
• Lung Cancer
• Autism
• Alzheimer’s
• Parkinson’s
• Multiple Sclerosis
• Neurofibromatosis
U.S. Army Medical *CDMRP
Research
and Materiel Command
is assisting with the execution of a specified portion of these appropriation(s)
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VRP Funding Synopsis
Congressional
Appropriations
FY 09-12
FY15
$10M
? Applications
Anticipate 18 Awards
FY13/14
$25M
$25M
147 Applications
34 Awards
94 Applications
33 Awards
U.S. Army Medical Research and Materiel Command
5
Sensory Clinical Capability Gaps
Visual Capability Gaps
•
Mitigation and treatment of traumatic
injuries, war-related injures, and diseases
to ocular structures and the visual system
Hearing and Balance Capability
Gaps
•
Hearing Restoration
•
Mitigation and treatment of visual
dysfunction and associated with TBI
•
Treatment of hearing loss
•
Prevention and/or treatment of tinnitus
•
Ocular and visual systems diagnostic
capabilities and assessment strategies
•
Epidemiology and measurement tools
for hearing loss
•
Eye protection and vision loss prevention
strategies
•
Prevention and Treatment of
vestibular dysfunction
•
Vision rehabilitation strategies and
quality of life measures
•
Epidemiological studies of military eye
trauma and TBI-related vision dysfunction
•
Vision restoration
•
Vision care education, training and
simulation
•
War fighter vision readiness and
enhancement
U.S. Army Medical Research and Materiel Command
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2009/10 Peer Reviewed VRP
 One program announcement – Maximum $2M per award
 120 Pre-proposals Received
 51
Selected for Full Proposal Submission
 49
Submitted Full Proposals
 $11,014,931
12
Investigators Selected for Funding
 10
Mitigation and treatment of visual dysfunction
associated with traumatic brain injury (TBI)
 1
Mitigation and treatment of traumatic injuries, warrelated injuries, and diseases to ocular structures and the
visual system
 1
Vision restoration
U.S. Army Medical Research and Materiel Command
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2011/12 Peer Reviewed VRP
 Two program announcements – II $1M, HD $250K
 151 Pre-proposals Received
 48
Selected for Full Proposal Submission
 45
Submitted Full Proposals
 $13,766,396
21 Investigators Selected for Funding
 7
Mitigation and treatment of traumatic injuries, warrelated injuries, and diseases to ocular structures and the
visual system
 8
Mitigation and treatment of visual dysfunction
associated with traumatic brain injury (TBI)
 5
Vision restoration
 1
Ocular and visual systems diagnostic capabilities and
assessment strategies
U.S. Army Medical Research and Materiel Command
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2013/14 Peer Reviewed VRP
 Two program announcements – TR $1M, HD $250K
 275 Pre-proposals Received
 151 Selected for Full Proposal Submission
 147 Submitted Full Proposals
 $24,868,891
34 Investigators Selected for Funding
 22
Mitigation and treatment of visual dysfunction
associated with traumatic brain injury (TBI)

5 Mitigation and treatment of traumatic injuries, warrelated injuries, and diseases to ocular structures and the
visual system

1 Rehabilitation strategies and quality of life measures

5 Vision restoration
U.S. Army Medical Research and Materiel Command
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Projects in Regards to Gaps
Gaps
VRP1 VRP2
VRP3
Total
One
1
8
22
31
Two
10
7
5
22
Three
1
Five
Seven
1
5
Total
12
21
U.S. Army Medical Research and Materiel Command
1
1
1
6
12
34
67
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Program Cycle
Release of
Program Announcement
~ May 2015
Office of the
Assistant
Secretary of
Defense
(Health Affairs)
Approval
Pre-Application
Receipt
Award
Negotiations
~ January 2016
Pre-Application
Screening
By 30 September 2016
Award Management
~ July 2015
NSRAA Panels
Programmatic
Review
Peer
Review
~ November 2015
Application
Receipt
~ October 2015
U.S. Army Medical Research and Materiel Command
Invitation
to Submit
~ August 2015
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Mechanism Focus
Supports both applied (preclinical) research and clinical trials addressing
specific focus areas:
Applied research is defined as work that refines concepts and ideas into
potential solutions with a view toward evaluating technical feasibility of
diagnostic and therapeutic techniques, clinical guidance, emerging
approaches and technologies, promising new products, and/or
pharmacologic agents.
A clinical trial is defined as a prospective accrual of human subjects where an
intervention (e.g., device, drug, biologic, surgical procedure, rehabilitative
modality, behavioral intervention, or other) is tested on a human subject for a
measurable outcome with respect to exploratory information, safety,
effectiveness, and/or efficacy. This outcome represents a direct effect on the
human subject of that intervention or interaction.
U.S. Army Medical Research and Materiel Command
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Goal of Two-Tier Review Process
To find scientifically meritorious proposals and
fund those that best fulfill program goals
Peer Review
Panels
Partnership
• Criterion-based evaluation of full
proposal
• Determination of “absolute”
scientific merit
• Outcome: Written critique and
scores for individual criteria and
overall merit
 No standing peer review panels
 No contact between reviewers and
Programmatic
Review Panels
• Comparison among proposals of high
scientific merit
• Determination of adherence to intent
and program relevance
• Outcome: Funding recommendations
applicants
U.S. Army Medical Research and Materiel Command
 No “pay line” (portfolio balance)
 Funds obligated up front; no out-year
budget commitments (but
milestones imposed)
 No continuation funding
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Thermo-Responsive Reversibly Attachable
Patch for Temporary Intervention in Ocular Trauma
Mark Humayun, MD PhD
University of Southern California
Study/Product Aim(s)
Catheter tip
• A biocompatible, reversibly adhesive patch fabricated
from pNIPAM-on-parylene stubstrates that meets the most
significant safety and efficacy concerns for treatment of
combat-related ocular trauma.
• Device key features that would be useful in combat
scenario:
(1) Easily reversible upon cooling without damaging the
healing tissue.
(2) Ease-of-use, allowing sutureless wound closure
enabling treatment in lower tiered (2o or lower) care
centers.
Approach
Key challenges at this stage of development are:
1) sterilization effects on adhesion,
2) environmental effects (temperature during transport) on
adhesion,
3) in vitro adhesion performance characterization and
4) preliminary biocompatibility.
These four areas will be investigated in a stop-gate
approach to assess whether this technology is viable to
continue to sustained biocompatibility testing.
1cc syringe
Loading port
Reaction chamber
Accomplishments this quarter:
• 18 animals have completed the in vivo sclerotomy study using our
injector tool (left) and an interim statistical analysis of IOP results has
begun(right).
• 5 Animals have completed in vivo peritomy study and additional animals
are being scheduled for the rest of this study.
• Enucleated eyes are being prepared for histological analysis to evaluate
healing progression and tissue response to hydrogel material.
Goals/Milestones
CY12 Q4 Goal: – Fabrication, Quality Characterization, Exposure Test
 Fabricate pNIPAM-parylene of different thicknesses (h=100nm, 400nm, 800m)
 Perform baseline characterization (contact angle vs. T and FTIR)
 Sterilize patches using either ETO sterilization or autoclave sterilization protocol
 Extreme Thermal Exposure of Patches (120oF or -50oF for 168hrs)
 Post-exposure characterization (Contact Angle vs. T and FTIR)
CY13 Goal – Performance Evaluation
 Evaluate effect of sterilization and temperature protocols on adhesion
characteristics; Evaluate ease of use of patches
 Initiate in vivo studies for scleral penetration closure and peritomy scarring
prevention.
CY14 Goal – Biocompatibility Assessment
 Complete in vivo studies and analyze data for summary report
U.S. Army Medical Research and Materiel Command
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Objective Methods to Test Visual Dysfunction in
the Presence of Cognitive Impairment
Randy Kardon, MD PhD
University of Iowa
Problem, Hypothesis and Military Relevance
• Addresses vision gap two: Models for Visual
Dysfunction Following Blast and Concussive Trauma.
• Specific areas of the visual pathway in the eye and brain can be
interrogated by a battery of visual stimuli designed to provide a
broad inventory of system-wide functioning after traumatic brain
injury.
• By applying these tests and validating them against standard
vision testing, patients and military personnel with visual
dysfunction can then be better diagnosed and characterized to
improve outcomes of therapeutic interventions.
Smart Eye (head and eye movement
tracking system
Hand held puplilometer – resulting in a
new chromatic stimulus and pupil test
Proposed Solution
• Objective is to use objective reflexes of the visual system to
diagnose vision deficits and ensure effective monitoring of their
treatment, when indicated.
• Aims: 1) In normal eyes, define range of values for pupil light
reflexes, evoked potentials and eye movements to targets
changing in resolution. 2) In eyes with damage to the retina or optic
nerve, define range of values for pupil light reflexes, evoked
potentials and eye movements to targets changing in resolution.
3) In eyes with damage to primary visual cortex (V1), define range
of values for perimetric pupil light reflexes, evoked potentials and
eye movements to targets changing in resolution.
• The successful outcome of this study will allow application of
objective tests to assess patients over a wider range of impaired
consciousness and cognitive dysfunction.
Activities
FY
Implementation of novel product-ready
hardware solutions
Testing in normal eyes
11
12
XXX
XXX
Testing in eyes with retinal or optic nerve
damage
XX
Testing in eyes with damage to primary
visual cortex
XX
Optimize hardware systems and vision
testing protocols
XXX
U.S. Army Medical Research and Materiel Command
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XX
XXX
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Wearable Visual Aid as Treatment for
TBI Associated Visual Dysfunction
James Weiland, PhD
University of Southern California
Problem, Hypothesis and Military Relevance
• Addresses vision gap seven: Regeneration and
Reconstruction of the Components of the Visual System
and Ocular Adnexa.
• A wearable system with advanced image sensors and
computer vision algorithms can provide the desired and
relevant information to individuals with TBI related injuries.
• The system will address major challenges encountered by
the blind, including detecting changes in elevation, guiding
safe street crossing, recognizing desired objects, and
orienting the user while navigating.
Proposed Solution
• Optimize a simultaneous localization and mapping (SLAM)
algorithm for use in obstacle detection for visually impaired
individuals during ambulation;
• Further develop neurally-inspired attention algorithms that
detect important objects in an environment for use by visually
impaired individuals during search tasks;
• Implement a highly miniaturized prototype wide field-of-view,
wide-dynamic range camera for image capture in indoor and
outdoor environments;
• Develop an algorithm for overall system control and integration,
including functionality for a user interface and adaptation to
different tasks and environments, and integrate the camera and
all algorithms into a wearable system.
• Test the portable system on visually impaired human subjects.
Activities
FY
11
12
Optimize SLAM for wearable
system
XXXX
XXXX
XXX
X
Further develop neurallyinspired attention algorithms
XXXX
XXXX
XXX
X
Implement wide field-of-view,
wide-dynamic range camera
XXXX
XXXX
XXX
X
Algorithm for system control
integrated with use interface
XXXX
XXXX
XXX
XXX
Test the portable system on
visually impaired volunteers
XXXX
XXXX
XXX
XXX
U.S. Army Medical Research and Materiel Command
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Other CDMRP Funded Vision
 2001 PRMRP
2 awards
$1.3M
 2002 PRMRP
1 award
$1.6M
 2003 PRMRP
1 award
$3.0M
 2006 PRMRP
8 awards
$7.5M
 2008 PRMRP
6 awards
$5.9M
 2008 DMRDP
4 awards
$6.0M
 2008 TSCRP
1 award
$0.5M
 2009 PH-TBI
2 awards
$4.1M
 2010 DMRDP
7 awards
$9.5M
 2011 AFIRM
1 award
$2.4M
 2011 DMRDP
2 awards
$4.7M
 2012 PRMRP
1 award
$1.4M
 2013 PH-TBI
1 award
$0.3M
37 awards
$48.2M
U.S. Army Medical Research and Materiel Command
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CDMRP & VRP Funded Vision Investigators
2001 PRMRP Gary Martinsen Russell McCally
2002 PRMRP Thomas Johnson
2003 PRMRP Darlene Dartt
2006 PRMRP Joe Rizzo Lu Chen Shelley Fried Kimberly Cockerham Michelle Callegan Balamurali Ambati Randy Kardon
De-Quan Li
2008 PRMRP Dean Li Joseph Sassani Kraig Bower Anthony Johnson Wolfgang Fink Irene Kochevar
2008 DRMRP Irene Kochevar Morgana Trexler Cathryn Sundback Anthony Johnson
2008 TSCRP Stephen Tsang
2009 PH-TBI Gang Luo Richard Hogle
2009/10 VRP Stacey Choi Kenneth Ciuffreda Colin Doherty Thao Nguyen Yury Petrov Uri Polat Richard Regueiro Tonia Rex
Gregory Schultz James Weiland Randy Kardon Nicholas Brecha
2010 DMRDP Richard Carvalho Gregory Liou Brian Lawrence Eli Peli Shigeo Tamiya Christopher Tyler Larry Benowitz
2011/12 VRP Eldon Geisert David Krizaj Mark Humayun Jena Steinle Andrew Hartwick Rajendra Kumar-Singh Cintia de Paiva
Andrew MacKay Shaomei Wang Jeffrey Goldberg Daniel Palanker Philip Troyk Sheila Nirenberg Michael Iuvone
Pavel Iserovich Kevin Park Walter Gray Brittany Coats Joseph Izatt Kenneth Ciuffreda James DeMar
2011 AFIRM Alexander Kiderman
2011 DMRDP Reza Dana Julie Haller
2012 PRMRP Stephen Plugfelder
2013 PH-TBI Alexander Kiderman
2013/14 VRP Joseph Brzezinski Alfredo Martinez Lora Likova Stephen Wong Cheryl Olman Shaochen Chen Kia Washington
William Jia Vijay Gorantla Jon Froehlich Derek Welsbie Samuel Fulcher Katherine Kajjar James Funderburgh
Jeffrey Mumm Douglas Dean James Akula Andrew Pieper Lu Chen Ali Djalilian Sanjoy Bhattachary Ricardo Carvalho
Sunil Chauhan Edward Chaum Joseph Ciolino Gere di Zerega David Kaplan Stephen Macknik Daniel Palanker Matthew Reilly
Lawrence Rizzolo Michael Steketee Morgana Trexler James DeMar
U.S. Army Medical Research and Materiel Command
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Thank You for Your Service!
U.S. Army Medical Research and Materiel Command
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Additional Hearing Slides
U.S. Army Medical Research and Materiel Command
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Clinical & Rehabilitative
Medicine Research Program
To increase understanding of the CRM Vision
Research Portfolio.
 Scope
 The Vision Traumatic Injury Restoration and
Rehabilitation portfolio includes DoD efforts in the
areas of visual dysfunction associated with traumatic
injury, with a view ranging from basic research
through clinical development
 Purpose
 Restore/rehabilitate the vision of Service Members
post-traumatic injury by advancing medical
capabilities (improved methods, drugs, and devices)
through research and development
U.S. Army Medical Research and Materiel Command
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Clinical & Rehabilitative
Medicine Research Program
To increase understanding of the CRM Hearing &
Balance Research Portfolio.
 Scope
 The Hearing and Balance Traumatic Injury Restoration
and Rehabilitation portfolio includes DoD efforts in the
areas of hearing and vestibular dysfunction associated
with traumatic injury, with a view ranging from basic
research through clinical development
 Purpose
 Restore/rehabilitate the hearing and balance of
Service Members post-traumatic injury by advancing
medical capabilities (improved methods, drugs, and
devices) through research and development
U.S. Army Medical Research and Materiel Command
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Sensory System
Investment of Active Projects
U.S. Army Medical Research and Materiel Command
23
Sensory Clinical Capability Gaps
Visual Capability Gaps
•
Mitigation and treatment of traumatic
injuries, war-related injures, and diseases
to ocular structures and the visual system
Hearing and Balance Capability
Gaps
•
Hearing Restoration
•
Mitigation and treatment of visual
dysfunction and associated with TBI
•
Treatment of hearing loss
•
Prevention and/or treatment of tinnitus
•
Ocular and visual systems diagnostic
capabilities and assessment strategies
•
Epidemiology and measurement tools
for hearing loss
•
Eye protection and vision loss prevention
strategies
•
Prevention and Treatment of
vestibular dysfunction
•
Vision rehabilitation strategies and
quality of life measures
•
Epidemiological studies of military eye
trauma and TBI-related vision dysfunction
•
Vision restoration
•
Vision care education, training and
simulation
•
War fighter vision readiness and
enhancement
U.S. Army Medical Research and Materiel Command
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Diagnosis and Treatment of Blast-Induced Hearing Loss
John S. Oghalai, MD
Stanford University, Stanford, CA
Problem, Hypothesis and Military Relevance
• Blast-induced hearing loss is common among active
military personnel.
• It produces a long-term disability that requires chronic
management through the Veterans Administration.
• Current treatments are limited to hearing aids.
• Hypothesis: Improved imaging of the ear and a detailed
understanding of the tissue, cellular, and genetic changes
that occur within the ear after blast injury will permit the
development novel and more effective treatments.
• Project: Rehabilitation; Task: Restoration and
Rehabilitation of Sensory System Traumatic Injury
Proposed Solution
(1) Novel Device to Image the Ear
after Blast Injury at High Resolution
(2) Cellular, Molecular, and Genetic
Characterization Studies to Identify
Novel Therapeutic Agents
Timeline and Cost
Activities
FY
• This proposal is designed to overcome current limitations
Aim 1a: Use our existing OCT device
via two parallel and transformative specific aims.
to characterize the anatomic patterns
• 1) To develop an endoscopic optical coherence
of damage after blast-injury in mice
tomography (OCT) device to image the ear at high
resolution. This aim will result in a safe, non-invasive, and
Aim 1b: Develop endoscopic OCT
portable device ready to be tested in humans.
device for use in humans
• 2) To develop a mouse model of blast injury to
Aim 2: Characterize the cellular,
characterize the cellular damage and changes in gene
molecular, and genetic patterns of
expression that occur after blast injury. This aim is
damage after blast-injury in mice
designed to identify molecular pathways of damage that
can be targeted by novel drugs.
• Collaborative
team:Research
1 clinician-scientist,
2 Command
U.S.research
Army Medical
and Materiel
bioengineers, and 2 neuroscientists.
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11
12
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Assessing the impact of blast-related sensory impairment
on multisensory integration while maneuvering on foot
Douglas Brungart, Ph.D. The Henry M. Jackson Foundation
Study Aim(s)
1: To assess the multisensory integration ability of normal Service Members by
characterizing aurally-aided visual search (AAVS) performance as a function of visual
target acquisition time and auditory localization accuracy while SMs are physically in
stationary or moving conditions.
2: To assess the multisensory integration ability of Service Members with sensory
impairment by characterizing their aurally-aided visual search times in the stationary and
moving conditions and to compare their performance to that of unimpaired Service
Members with similar visual target acquisition times and auditory localization scores.
3. To determine the extent to which the aurally-aided visual search performance of
stationary and moving Service Members with sensory impairment can be predicted from
current clinical measures of neurological, sensory and vestibular function.
4. For those participants who proceed to the second phase of the study, to learn more
about the neurophysiological underpinnings of sensory integration disorder by comparing
results from virtual reality (Computer Assisted Rehabilitation Environment, CAREN) to an
experimental environment (Magnetoencephalography, MEG)
Approach
The study will take an aurally-aided visual search paradigm that has been shown to be
effective for assessing audio-visual integration in stationary environments and port it to
a moving platform that will greatly increase the sensory load and simulate dismounted
combat operations.
Timeline and Cost
Activities
FY
Recruit study personnel; implement spatial sound
array in CAREN; obtain IRB approval
Collect AAVS data on stationary and moving control
subjects
Collect AAVS data on stationary and moving
impaired subjects
Analyze and report results
13
14
The blue dots show the locations of the 64 loudspeakers used in the
experiment. These speakers are mounted on an aluminum scaffold behind the
fabric screen of the CAREN.
Milestones and Goals
15
FY 13 Goals
 Develop, build, and integrate spatial sound array in CAREN system (Done)
 Obtain IRB Approval (Done)
FY14 Goals
 Begin collecting AAVS data on control subjects (2 Completed)
 Begin collecting AAVS data on impaired subjects
FY15 Goal
 Develop a model of visual search time for normal and impaired subjects
 Analyze and report results
Project Status: Green
All projected milestones have been met and current expenditures are under
projected budget.
U.S. Army Medical Research and Materiel Command
Updated: 10/31/2014
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