IMIA Working Group 6 Medical Concept Representation Focus of Meeting: Scientific developments:...

IMIA Working Group 6IMIA Working Group 6Medical Concept RepresentationMedical Concept Representation

Focus of Meeting:Focus of Meeting:

Scientific developments:Scientific developments: foundational issues foundational issues rather than operational questionsrather than operational questions

Scientific developments:Scientific developments: foundational issues foundational issues rather than operational questionsrather than operational questions

New role of ontological research New role of ontological research for new age of biomedical informaticsfor new age of biomedical informatics

New role of ontological research New role of ontological research for new age of biomedical informaticsfor new age of biomedical informatics

Long-term view: Long-term view: ensure development of robustensure development of robustbiomedical ontologies for the futurebiomedical ontologies for the future

Long-term view: Long-term view: ensure development of robustensure development of robustbiomedical ontologies for the futurebiomedical ontologies for the future

The Foundational Role of AnatomyThe Foundational Role of Anatomyfor Biomedical Ontologiesfor Biomedical Ontologies

Cornelius Rosse M.D., D.Sc.S t r u c t u r a l I n f o r m a t i c s G r o u pS t r u c t u r a l I n f o r m a t i c s G r o u p

University of WashingtonUniversity of Washington




What will be the take home message?What will be the take home message?

What are the problems?What are the problems?

If a scienceIf a scienceWhat is its theoretical foundation?What is its theoretical foundation?What is its methodology?What is its methodology?


We have established biomedical informaticsWe have established biomedical informaticsIs it a service?Is it a service?Is it a new biomedical science?Is it a new biomedical science?


Are theory and ontological methodology applied in Are theory and ontological methodology applied in the practice of biomedical informatics?the practice of biomedical informatics?


How do applications of theory and methodology supportHow do applications of theory and methodology support inference about individuals (EHR)?inference about individuals (EHR)?



What are the solutions?What are the solutions?

Theoretical solutionTheoretical solution Propose a theory for biomedical realityPropose a theory for biomedical reality

derived from top-level ontologiesderived from top-level ontologies

Methodological solutionMethodological solutionDevelop reference ontologies inDevelop reference ontologies in

domains of empirical basic biomedical domains of empirical basic biomedical sciencescience

using sound methodologyusing sound methodologyReuse reference ontologies in Reuse reference ontologies in

application ontologies designed for application ontologies designed for clinical specialtiesclinical specialtiesbiomedical researchbiomedical researcheducation and trainingeducation and training







Case study: Cardiac CycleCase study: Cardiac Cycle


Atrial pressureAtrial pressure



Left ventricular pressureLeft ventricular pressure


Left ventricular volumeLeft ventricular volume




Aortic pressureAortic pressure


Left ventricular volumeLeft ventricular volume



Task:Generate ontological representation

Resourcesextant terminologies:

UMLS

Cardiac Cycle in UMLSCardiac Cycle in UMLS


Task:

Generate ontological representation of cardiac cycle

Resources

extant terminologies: UMLS

textbooks, literature

re-examination of cardiac cycle from ontological perspective

Diversion!Diversion!

Task:

Generate ontological representation of cardiac cycle

Resources

extant terminologies: UMLS

textbooks, literature

re-examination of cardiac cycle from ontological perspective

Constitutents of Medical ScienceConstitutents of Medical Science

Basic sciences Clinical sciences

Constituents of Medical ScienceConstituents of Medical Science

Basic sciences Clinical sciences

Physiology Internal medicinePathology Pediatrics Microbiology PsychiatryBiochemistry AnesthesiologyAnatomy Surgery

macroscopic general surgerymicroscopic maxillofacial surgeryembryology otolaryngology neuroanatomy neurosurgery

Basic SciencesBasic Sciences

CharacteristicsCharacteristics

Concerned with canonical knowledgeConcerned with canonical knowledgenot data pertaining to individualsnot data pertaining to individuals


Taught/learned duringTaught/learned during first phase of professional trainingfirst phase of professional training


Do not target specialties in clinical medicineDo not target specialties in clinical medicineDo not target specialties in clinical medicineDo not target specialties in clinical medicine

Need to be relearned in context of medical specialtiesNeed to be relearned in context of medical specialtiesNeed to be relearned in context of medical specialtiesNeed to be relearned in context of medical specialties

PurposePurpose

Provide general understanding for Provide general understanding for reasoning and managing datareasoning and managing data

pertaining to individualspertaining to individuals




Changing Environment

1960’s: curricular reform1970’s: new biology


Changing Environment

1960’s: curricular reform1970’s: new biology

Medicine Biomedicine; Biomedical science

Constituents of Constituents of BiomedicalBiomedical Science Science

Basic sciences Clinical sciencesPhysiology Internal medicinePathology Pediatrics Microbiology PsychiatryBiochemistry AnesthesiologyAnatomy Surgery

macroscopic general surgerymicroscopic maxillofacial surgeryembryology otolaryngology neuroanatomy neurosurgery

Traditional disciplines

New biologyNew biology New medicineNew medicine molecular and cell biologymolecular and cell biology molecular medicine molecular medicine genomics, proteomicsgenomics, proteomics regenerative medicine regenerative medicine developmental biologydevelopmental biology translational medicine translational medicine systems biologysystems biology nuclear medicine nuclear medicine

What is Biomedical Informatics?What is Biomedical Informatics?

Basic sciences Clinical sciencesPhysiology Internal medicinePathology Pediatrics Microbiology PsychiatryBiochemistry AnesthesiologyAnatomy Surgery

macroscopic general surgery

microscopic maxillofacial surgery

embryology otolaryngology neuroanatomy neurosurgery

Traditional disciplines

New biologyNew biology New medicineNew medicine molecular and cell biologymolecular and cell biology molecular medicine molecular medicine genomics, proteomicsgenomics, proteomics regenerative medicine regenerative medicine developmental biologydevelopmental biology translational translational medicinemedicine systems biology systems biology nuclear medicine nuclear medicine

Biomedical InformaticsBiomedical Informatics

Attributes of ScienceAttributes of Science

Science hasScience has

a.) theories on basis of which a.) theories on basis of which hypotheses can be formulatedhypotheses can be formulated

b.) methodology which can test the hypothesesb.) methodology which can test the hypotheses

Best hope:Best hope: OntologyOntology

Need for theories and methodologyNeed for theories and methodology

What is ontology ?What is ontology ?

Smith (1996):Smith (1996): ““the science which deals with the nature and organization of reality”the science which deals with the nature and organization of reality”

Grenon, Smith & Goldberg (2004)Grenon, Smith & Goldberg (2004) ““An ontology grasps the entities which exist within a given portion of An ontology grasps the entities which exist within a given portion of the world at a given level of generality. It includes a taxonomy of the the world at a given level of generality. It includes a taxonomy of the types of entities and relations that exist in that portion of the world types of entities and relations that exist in that portion of the world seen from a given perspective.” seen from a given perspective.”

Ontological theoriesOntological theoriesderive from the philosophy of realityderive from the philosophy of reality

Ontological methodologyOntological methodology creates an artifact which depicts a portion of the world creates an artifact which depicts a portion of the world

seen from a given perspectiveseen from a given perspective

Need for theories and methodologyNeed for theories and methodology

What is ontology ?What is ontology ? first meaning:first meaning:

Smith (1996):Smith (1996): ““the science which deals with the nature and organization of realitythe science which deals with the nature and organization of reality

Grenon, Smith & Goldberg (2004)Grenon, Smith & Goldberg (2004) ““An ontology grasps the entities which exist within a given portion of An ontology grasps the entities which exist within a given portion of the world at a given level of generality. It includes a taxonomy of the the world at a given level of generality. It includes a taxonomy of the types of entities and relations that exist in that portion of the world types of entities and relations that exist in that portion of the world seen from a given perspective.” seen from a given perspective.”

second meaning:second meaning:

an artifact an artifact projects to a given domain of reality projects to a given domain of reality created through the application of created through the application of

principles and methods of ontological scienceprinciples and methods of ontological science

AmbiguityAmbiguity- any domain discourse is full with itany domain discourse is full with ithumans are adapt at dealing with ithumans are adapt at dealing with it

- printed page tolerates it- printed page tolerates it- computational inference will becomputational inference will be

crippled by itcrippled by it

Why base an ontology on reality?Why base an ontology on reality?

AmbiguityAmbiguity- any domain discourse is full with itany domain discourse is full with it

- humans are adapt at dealing with ithumans are adapt at dealing with it

- printed page tolerates it- printed page tolerates it

- computational inference will becomputational inference will be

crippled by itcrippled by it

Conclusion:Conclusion:- we have to base ontology on reality- we have to base ontology on reality

- need to take a new look at reality- need to take a new look at reality

Why base an ontology on reality?Why base an ontology on reality?

What kinds of ontologies are there?What kinds of ontologies are there?

1.1. Formal, top-level ontologiesFormal, top-level ontologies

2. Domain reference ontologies2. Domain reference ontologies

3. Terminology-based application ontologies3. Terminology-based application ontologies


1.1. Formal, top-level ontologies:Formal, top-level ontologies: DOLCE, BFODOLCE, BFO

domain-independent theoriesdomain-independent theories framework of axioms and definitionsframework of axioms and definitions

high degree of representational accuracyhigh degree of representational accuracydesigned to be used as controls on other types of ontologiesdesigned to be used as controls on other types of ontologies





2. Domain reference ontologies:2. Domain reference ontologies: FMAFMA

declare a theory about a particular domain of realitydeclare a theory about a particular domain of realitymake use of methods of top-level ontologiesmake use of methods of top-level ontologiesgeneral purpose resourcesgeneral purpose resourcesgeneralize to other domains generalize to other domains

anatomy generalizes to physiology, surgeryanatomy generalizes to physiology, surgery





2. Domain reference ontologies:2. Domain reference ontologies: FMAFMA

declare a theory about a particular domain of realitydeclare a theory about a particular domain of realitymake use of methods of top-level ontologiesmake use of methods of top-level ontologiesgeneral purpose resourcesgeneral purpose resourcesgeneralize to other domains generalize to other domains

anatomy generalizes to physiology, surgeryanatomy generalizes to physiology, surgery

3. Terminology-based application ontologies:3. Terminology-based application ontologies: GO, other OBO, SNOMED, MeSHGO, other OBO, SNOMED, MeSH

systems of termssystems of termspurpose-builtpurpose-builtdesigned to meet particular needsdesigned to meet particular needs

annotating databases, medical dataannotating databases, medical data

Basic Formal OntologyBasic Formal Ontology

Entities Entities

Occurrents Occurrents

ContinuantsContinuants

Distinguishing criterion (differentia): TimeDistinguishing criterion (differentia): Time

Entities Entities

OccurrentsOccurrents - SPAN entities- SPAN entities

Dependent entities which do not endure through time;

unfold themselves in successive temporal phases

(e.g., processes, actions) have temporal partshave temporal parts


Entities Entities

OccurrentsOccurrents - SPAN entities- SPAN entities Dependent entities which do not endure through time;

unfold themselves in successive temporal phases(e.g., processes, actions)

have temporal partshave temporal parts

ContinuantsContinuants - SNAP entities- SNAP entities Entities which endure in toto

in every instant of time at which they exist have spatial parts

Independent continuants objects, components

Dependent continuants

attributes, roles, qualities, functions


END OF DIVERSION

Biological occurrentBiological occurrent

Biological entityBiological entity

Biological continuantBiological continuantis-a

A theory of biomedical realityA theory of biomedical reality


Extra-organismal biological continuant



Biological continuantBiological continuant

Organismalcontinuant


is-a


Independent organismal continuant


Dependent organismal continuant








is-a








Materialanatomical

entity

Materialanatomical

entity

Materialpathological

entity


entity





Anatomical structure Canonical anatomical structure Variant anatomical structurePortion of canonical body substance Portion of blood Portion of cytosol

Pathological structure Neoplasm Inflammatory structure Degenerated structurePortion of pathological body substance Portion of pus Portion of amyloid

is-a








Materialanatomical

entity

Materialanatomical

entity


entity


entity


Immaterialanatomical continuant


Physiological continuant


Immaterialpathological continuant







Anatomical space Cavity of lysosomeAnatomical surface E-face of plasma membraneAnatomical lineAnatomical point

Function Secrete Flex; ExtendPhysiological state Relaxed state Contracted statePhysiological role Antagonist

Pathological space Cavity of abscessPathological surface Boundary of tumorMalfunction Atrial fibrillationPathological state MalnutritionPathological role

is-a








Materialanatomical

entity

Materialanatomical

entity


entity


entity














Function Secrete Flex; ExtendPhysiological state SystolePhysiological role Antagonist


Organismal occurrent


Extra-organismal biological occurrent


is-a








Materialanatomical

entity

Materialanatomical

entity


entity


entity




















Pathologicalprocess

Pathologicalprocess

Physiologicalprocess


Secreting Secreting insulinTranscribing RNA

MutatingMetastasizingNecrosing

is-a








Materialanatomical

entity

Materialanatomical

entity


entity


entity




















Pathologicalprocess

Pathologicalprocess





Ontology of Biomedical Reality (OBR)

is-a

Definition: Material physical anatomical entity which has inherent 3D shape; generated by coordinated expression of the organism's own structural genes;



Materialanatomical

entity

Materialanatomical

entity


entity


entity



Anatomical structure

Theory of biological continuantsTheory of biological continuants

BodyPart

BodyPart

HumanBody

HumanBody

OrganSystem

OrganSystemOrganOrganCellCell Organ

Part

OrganPart

Portionof tissue

Portionof tissue

AnatomicalStructure

AnatomicalStructure

CellPart

CellPart

BiologicalMacromolecule


AcellularAnatomicalStructure



Material Physical Anatomical Entity


BodyPart

BodyPart

HumanBody

HumanBody

OrganSystem


Part

OrganPart

Portionof tissue

Portionof tissue

AnatomicalStructure

AnatomicalStructure

Portion ofbody substance


CellPart

CellPart








BodyPart

BodyPart

HumanBody

HumanBody

OrganSystem


Part

OrganPart

Portionof tissue

Portionof tissue

AnatomicalStructure

AnatomicalStructure



CellPart

CellPart










BodyPart

BodyPart

HumanBody

HumanBody

OrganSystem


Part

OrganPart

Portionof tissue

Portionof tissue

AnatomicalStructure

AnatomicalStructure



CellPart

CellPart







Non-material Physical Anatomical Entity


SpaceSpace SurfaceSurface LineLine






BodyPart

BodyPart

HumanBody

HumanBody

OrganSystem


Part

OrganPart

Portionof tissue

Portionof tissue

AnatomicalStructure

AnatomicalStructure



CellPart

CellPart









SpaceSpace SurfaceSurface LineLine



FMA: created with ontological methods FMA: created with ontological methods

Ontological methodsOntological methods

Somatic cell which has as direct parts of its cytoplasm myofibrils organized in various patterns.

Muscle cell which has as its direct parts myofilaments organized into sarcomeres.

Muscle cell which has as its direct parts myofilaments organized into sarcomeres.

Striated muscle cell which has as its direct parts one or two centrally placed nuclei.

Continuants in Cardiac CycleContinuants in Cardiac Cycle

ParticipantsParticipants

Biatrial partof heart

Biventricular partof heart

Fibrouspericardium

Pericardial cavity

How do we represent pathological continuants?How do we represent pathological continuants?


Will the processes remainnormal?

Can we propose a theory of Can we propose a theory of biological processes?biological processes?

Rationale for theory of continuants:Rationale for theory of continuants:

based on gene expression of dependent continuantsbased on gene expression of dependent continuantscompatible with theory of OBRcompatible with theory of OBR

Rationale for theory of processes:Rationale for theory of processes:

need to formulate a hypothesisneed to formulate a hypothesisevaluate it through instantiation of evaluate it through instantiation of

physiological and pathological processesphysiological and pathological processes

Can we propose a theory of Can we propose a theory of biological processes?biological processes?

A process is an occurrent which is realized through the conversion of physical energy of one kind to another or to a change in structural order.

Start with a hypothesis:Start with a hypothesis:

Theory of biological processesTheory of biological processes


HypothesisHypothesis::

Rationale:Rationale:processes involve processes involve

movement of their participantsmovement of their participantscaused by some forcecaused by some force

generated by dissipation of energygenerated by dissipation of energy

Where is energy generated?

Sarcomere

SarcomereSarcomere

Ca++

Conversion of energy from one kind to anotherConversion of energy from one kind to another

Liberated energy

Conversion of chemical to mechanical energy

Molecular conformational change

Transmission of force by participants in cardiac cycle

Macromolecule

Movie OPERATORS

How do we classify processes?How do we classify processes?

PProcessrocess is is -- an occurrent which is realized through the an occurrent which is realized through the

conversion of physical energy of one kind to conversion of physical energy of one kind to another or another or to a change in structural orderto a change in structural order

- - a transformation of one state of an occurrent a transformation of one state of an occurrent into another state.into another state.

-- a change in the values of the set of attributes a change in the values of the set of attributes that that define a state.define a state.

Definition


PProcessrocess is is -- an occurrent which is realized through the conversion of physical an occurrent which is realized through the conversion of physical energy of one kind to another or to a change in structural order. energy of one kind to another or to a change in structural order.

- - a transformation of one state of an occurrent into another state.a transformation of one state of an occurrent into another state.

-- a change in the values of the set of attributes that define a state a change in the values of the set of attributes that define a state

SStatetate is is a dependent continuant specified by the values of a a dependent continuant specified by the values of a set of attributes.set of attributes.

Definition


PProcessrocess is is -- an occurrent which is realized through the conversion of physical an occurrent which is realized through the conversion of physical energy of one kind to another or to a change in structural order. energy of one kind to another or to a change in structural order.

- - a transformation of one state of an occurrent into another state.a transformation of one state of an occurrent into another state.

-- a change in the values of the set of attributes that define a state a change in the values of the set of attributes that define a state

SStatetate is is a dependent continuant specified by the values of a set of attributesa dependent continuant specified by the values of a set of attributes

A biological process isa process the direct participants of which are one or more

anatomical entities

Definition

Can OBR accommodate constituents of cardiac cycle? Can OBR accommodate constituents of cardiac cycle?






Pathologicalprocess

Pathologicalprocess



Need to deal withNeed to deal with non-biological participantsnon-biological participants

Ca++ Ca++ non-biological processesnon-biological processes

chemical bonding and bond breakingchemical bonding and bond breakingattributes and operatorsattributes and operators

generalize to non-biological domainsgeneralize to non-biological domains Laws of physics and chemistry operate in Laws of physics and chemistry operate in

biological and non-biological domains of realitybiological and non-biological domains of reality

Conflict with OBRConflict with OBR






Pathologicalprocess

Pathologicalprocess



Need to deal withNeed to deal with non-biological participantsnon-biological participants

Ca++ Ca++ non-biological processesnon-biological processes

chemical bonding and bond breakingchemical bonding and bond breakingattributes and operatorsattributes and operators

generalize to non-biological domainsgeneralize to non-biological domains Laws of physics and chemistry operate in Laws of physics and chemistry operate in

biological and non-biological domains of realitybiological and non-biological domains of reality

OBR hypothesis must be modified

Acyclic processAcyclic process


ProcessProcess

Cyclic processCyclic process


Myosin-actinbinding-unbinding


Myosin headflexure-unflexure



ProcessProcess


Calcium-troponinbinding-unbinding


Sliding of myofilaments


Shortening of sarcomere


Contractionmyocyte

myocardial loop

Contractionmyocyte

myocardial loop

Increase in LV blood pressure


Flowing ofLV blood to aorta


Cardiac cyclingCardiac cycling


Chemical-to-chemical

energy

Chemical-to-chemical

energy

Molecular conformational

change

Molecular conformational

changeMyosin-actin

binding-unbinding





ProcessProcess


Chemical-to-mechanical

energy

Chemical-to-mechanical

energy



Mechanical-to-mechanical

energy

Mechanical-to-mechanical

energy





Contractionmyocyte

myocardial loop

Contractionmyocyte

myocardial loop

Mechanical-to-fluid potential

energy

Mechanical-to-fluid potential

energy





Fluid potential-to-fluid kinetic

energy

Fluid potential-to-fluid kinetic

energy

Chemical-to-fluid dynamic

energy

Chemical-to-fluid dynamic

energy

Cardiac cyclingCardiac cycling

Testing the ‘Process’ hypothesisTesting the ‘Process’ hypothesis


HypothesisHypothesis::

Rationale:Rationale:processes involve processes involve

movement of their participantsmovement of their participantscaused by some forcecaused by some force

generated by dissipation of energygenerated by dissipation of energy

Testing of hypothesis:Testing of hypothesis:rooted in non-equilibrium thermodynamics rooted in non-equilibrium thermodynamics first classification trial yields results first classification trial yields results

intuitive at the operational levelintuitive at the operational level

conform to single inheritanceconform to single inheritance

How do we classify non-biological entities?How do we classify non-biological entities?

How do we classify physical attributes?How do we classify physical attributes?

How do we classify operators?How do we classify operators?

Fibrouspericardium

Pericardial cavity

How do we represent pathological pathological processes?How do we represent pathological pathological processes?








Materialanatomical

entity

Materialanatomical

entity


entity


entity




















Pathologicalprocess

Pathologicalprocess





Ontology of Biomedical Reality (OBR)

is-a

Physical occurrentPhysical occurrent

Entity ofPhysical Reality


Physical continuantPhysical continuant

ProcessProcessDimensionalcontinuant

Dimensionalcontinuant

Non-dimensionalcontinuant


Spatio-temporal

worm

Spatio-temporal

worm







Immaterialdimensional continuant


Biological material continuantBiological material continuant

Non-biological material continuantNon-biological material continuant

Materialdimensional continuant


Non-biological immaterial continuantNon-biological immaterial continuant

Biological immaterial continuantBiological immaterial continuant



Spatiotemporal

worm

Spatiotemporal

worm

















AttributeAttribute

OperatorOperator Structural operatorStructural operator

Attribute operatorAttribute operator

Biological operatorBiological operator

Material attributeMaterial attribute

Process attributeProcess attribute

Spatial attributeSpatial attribute

StateState

FunctionFunction

RoleRole

Spatiotemporal

worm

Spatiotemporal

worm





ProcessProcess















AttributeAttribute







StateState

FunctionFunction

RoleRole

Spatio-temporal

worm

Spatio-temporal

worm

Cardiac cyclingKreb’s cycle

Control processMorphogenetic processReplication processDegeneration process

Ontology of Physical Reality (OPR)





ProcessProcess















AttributeAttribute







StateState

FunctionFunction

RoleRole

Spatiotemporal

worm

Spatiotemporal

worm

Cardiac cycleKreb’s cycle

Control processMorphogenetic processReplication processDegeneration process

Ontology of Physical Reality (OPR)

Anatomical Structure

What about our case study: Cardiac Cycle?What about our case study: Cardiac Cycle?

ProtégéProtégé

a physiological-chemical to fluid kinetic energy change which has as its direct anatomical participants the heart and the portion of blood in the heart



If biomedical informatics is to be a scienceIf biomedical informatics is to be a scienceWhat is the theoretical foundation?What is the theoretical foundation?What is its methodology?What is its methodology?

If biomedical informatics is to be a scienceIf biomedical informatics is to be a scienceWhat is the theoretical foundation?What is the theoretical foundation?What is its methodology?What is its methodology?








CharacteristicsCharacteristics





Do not target specialties in clinical medicineDo not target specialties in clinical medicineDo not target specialties in clinical medicineDo not target specialties in clinical medicine

Need to be relearned in context of medical specialtiesNeed to be relearned in context of medical specialtiesNeed to be relearned in context of medical specialtiesNeed to be relearned in context of medical specialties

PurposePurpose






1.1. Formal, top-level ontologiesFormal, top-level ontologies

2. Domain reference ontologies2. Domain reference ontologies

3. Terminology-based application ontologies3. Terminology-based application ontologies


What are the solutions?What are the solutions?













AttributeOperator

Material or Spatial

Attribute

Structuraloperator

Biologicaloperator

ProcessAttribute


Process

Attribute

Continuant

Operator

Process

Need for dynamically defining

disciplinary boundaries

Traditional basic science: anatomy

AttributeOperator

Material or Spatial

Attribute

Structuraloperator

Biologicaloperator

ProcessAttribute


Process

Attribute

Continuant

Operator

Process

Traditional basic science:Physiology and Pathophysiology

AttributeOperator

Material or Spatial

Attribute

Structuraloperator

Biologicaloperator

change attribute values

has participantshas role-player attributes

has attributeshas part

ProcessAttribute

has attribute


create ordestroy

create ordestroy

Process

Attribute

Continuant

Operator

Process

The Foundational Role of AnatomyThe Foundational Role of Anatomyfor Biomedical Ontologiesfor Biomedical Ontologies






IMIA Working Group 6 Medical Concept Representation Focus of Meeting: Scientific developments:...

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