Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease...
-
Upload
hector-rich -
Category
Documents
-
view
215 -
download
2
Transcript of Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease...
![Page 1: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/1.jpg)
Disease, and Other Clinical Natural Kinds
Barry Smith
Gradualist Approaches to Health and DiseaseBerlin, March 23, 2012
1
![Page 2: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/2.jpg)
Natural Kind
2/
Synonyms: universal, type
= entities of the sorts which are referred to by general terms of natural science
Instances, particulars, individuals
= entities of the sorts which can be observed in experiments of natural science
![Page 3: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/3.jpg)
Old biology data
3/
![Page 4: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/4.jpg)
MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDV
New biology data
4
![Page 5: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/5.jpg)
How to do biology across the genome?MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVMKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVMKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVMKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDV
5
![Page 6: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/6.jpg)
how to link the kinds of phenomena represented here
6/
![Page 7: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/7.jpg)
or here
7
![Page 8: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/8.jpg)
or here
8
![Page 9: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/9.jpg)
MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPIPSKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDSFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVVAGEAASSNHHQKISRVTRKRPREPKSTNDILVAGQKLFGSSFEFRDLHQLRLCYEIYMADTPSVAVQAPPGYGKTELFHLPLIALASKGDVEYVSFLFVPYTVLLANCMIRLGRRGCLNVAPVRNFIEEGYDGVTDLYVGIYDDLASTNFTDRIAAWENIVECTFRTNNVKLGYLIVDEFHNFETEVYRQSQFGGITNLDFDAFEKAIFLSGTAPEAVADAALQRIGLTGLAKKSMDINELKRSEDLSRGLSSYPTRMFNLIKEKSEVPLGHVHKIRKKVESQPEEALKLLLALFESEPESKAIVVASTTNEVEELACSWRKYFRVVWIHGKLGAAEKVSRTKEFVTDGSMQVLIGTKLVTEGIDIKQLMMVIMLDNRLNIIELIQGVGRLRDGGLCYLLSRKNSWAARNRKGELPPKEGCITEQVREFYGLESKKGKKGQHVGCCGSRTDLSADTVELIERMDRLAEKQATASMSIVALPSSFQESNSSDRYRKYCSSDEDSNTCIHGSANASTNASTNAITTASTNVRTNATTNASTNATTNASTNASTNATTNASTNATTNSSTNATTTASTNVRTSATTTASINVRTSATTTESTNSSTNATTTESTNSSTNATTTESTNSNTSATTTASINVRTSATTTESTNSSTSATTTASINVRTSATTTKSINSSTNATTTESTNSNTNATTTESTNSSTNATTTESTNSSTNATTTESTNSNTSAATTESTNSNTSATTTESTNASAKEDANKDGNAEDNRFHPVTDINKESYKRKGSQMVLLERKKLKAQFPNTSENMNVLQFLGFRSDEIKHLFLYGIDIYFCPEGVFTQYGLCKGCQKMFELCVCWAGQKVSYRRIAWEALAVERMLRNDEEYKEYLEDIEPYHGDPVGYLKYFSVKRREIYSQIQRNYAWYLAITRRRETISVLDSTRGKQGSQVFRMSGRQIKELYFKVWSNLRESKTEVLQYFLNWDEKKCQEEWEAKDDTVVVEALEKGGVFQRLRSMTSAGLQGPQYVKLQFSRHHRQLRSRYELSLGMHLRDQIALGVTPSKVPHWTAFLSMLIGLFYNKTFRQKLEYLLEQISEVWLLPHWLDLANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDGRFDILLCRDSSREVGELIGLFYNKTFRQKLEYLLEQISEVWLLPHWLDLANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDGRFDILLCRDSSREVGELIGLFYNKTFRQKLEYLLEQISEVWLLPHWLDLANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDGRFDILLCRDSSREVGE
9
to this?
![Page 10: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/10.jpg)
10
or this?
![Page 11: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/11.jpg)
answer: through annotation of data with terms from a controlled vocabulary or ‘ontology’
11
sphingolipid transporter activity
Holliday junction helicase complex
![Page 12: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/12.jpg)
this allows integration of databases
MouseEcotope GlyProt
DiabetInGene
GluChem
Holliday junction helicase complex
13
![Page 13: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/13.jpg)
and supports logical reasoning over data
15
![Page 14: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/14.jpg)
‘Ontology’ in PubMed
16/24
![Page 15: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/15.jpg)
GO, in particular, is tremendously successful
17
![Page 16: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/16.jpg)
$100 million invested in literature and data curation using GO
over 11 million annotations relating gene products described in the UniProt, Ensembl and other databases to GO termsexperimental results reported in 52,000 scientific journal articles manually annoted by expert biologists using GO
18
![Page 17: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/17.jpg)
1. rooted in basic experimental biology
2. links people to data and to literature
3. links data to data
• across species (human, mouse, yeast, fly ...)
• across granularities (molecule, cell, organ, organism, population)
4. links medicine to biological science
5. promotes cumulation of scientific knowledge in algorithmically tractable form
19
Benefits of the GO
![Page 18: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/18.jpg)
National Center for Biomedical Ontology (NIH Roadmap Center)
24
− Stanford Biomedical Informatics Research− The Mayo Clinic− University at Buffalo Department of
Philosophy
http://bioportal.bioontology.org
![Page 19: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/19.jpg)
25
![Page 20: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/20.jpg)
26
![Page 21: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/21.jpg)
GO supports only three types of annotation
27
what cellular component?
what molecular function?
what biological process?
no diseases in GO
![Page 22: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/22.jpg)
28
![Page 23: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/23.jpg)
29
RELATION TO TIME
GRANULARITY
CONTINUANT OCCURRENT
INDEPENDENT DEPENDENT
ORGAN ANDORGANISM
Organism(NCBI
Taxonomy)
Anatomical Entity(FMA, CARO)
OrganFunction
(FMP, CPRO) Phenotypic
Quality(PaTO)
Biological Process
(GO)CELL AND CELLULAR
COMPONENT
Cell(CL)
Cellular Compone
nt(FMA, GO)
Cellular Function
(GO)
MOLECULEMolecule
(ChEBI, SO,RnaO, PrO)
Molecular Function(GO)
Molecular Process
(GO)
OBO Foundry (first version, 2006)Yellow = Gene Ontology
![Page 25: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/25.jpg)
Current OBO Foundry Ontologies
• Biological process (GO)• Cellular component (GO)• Chemical entities of biological interest• Molecular function (GO)• Phenotypic quality• PRotein Ontology (PRO)• Xenopus Anatomy and Development• Zebrafish Anatomy and Development
31
![Page 26: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/26.jpg)
Foundry ontologies under review
Cell Ontology (CL)Foundational Model of Anatomy (FMA)Infectious Disease Ontology (IDO)
Staph. aureus Ontology (IDO Sa)
Malaria Ontology (IDO MAL)
Influenza Ontology (IDO Flu)
HIV Ontology (IDO HIV)
Ontology for Biomedical Investigations (OBI)Ontology for General Medical Sciences (OGMS)Plant Ontology (PO)
32
![Page 27: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/27.jpg)
Ontologies under construction
Allergy OntologyEnvironment Ontology (EnvO) Immunology Ontology (IDO)Mental Functioning Ontology (MFO)
Emotion Ontology (MFO-EM)Pain Ontology
Mental Disease Ontology (MDO)Neurological Disease Ontology (ND)Vaccine Ontology (VO)
33
![Page 28: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/28.jpg)
34
FMA has 83281 types and 3 million relations representing canonical adult human anatomy= the anatomy generated by the coordinated expression of the organism’s own structural genes.
Canonical ≠ statistically normal
32 teethtwo arms two legs
one nosetwo nostrilstwo kidneys, …
Foundational Model of Anatomy Ontology
![Page 29: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/29.jpg)
Foundational Model of Anatomy (FMA)
Pleural Cavity
Pleural Cavity
Interlobar recess
Interlobar recess
Mesothelium of Pleura
Mesothelium of Pleura
Pleura(Wall of Sac)
Pleura(Wall of Sac)
VisceralPleura
VisceralPleura
Pleural SacPleural Sac
Parietal Pleura
Parietal Pleura
Anatomical SpaceAnatomical Space
OrganCavityOrganCavity
Serous SacCavity
Serous SacCavity
AnatomicalStructure
AnatomicalStructure
OrganOrgan
Serous SacSerous Sac
MediastinalPleura
MediastinalPleura
TissueTissue
Organ PartOrgan Part
Organ Subdivision
Organ Subdivision
Organ Component
Organ Component
Organ CavitySubdivision
Organ CavitySubdivision
Serous SacCavity
Subdivision
Serous SacCavity
Subdivision
part
_of
is_a
35
![Page 30: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/30.jpg)
An ontology
is a controlled structured vocabulary
that includes a backbone taxonomy (nodes connected by the is_a [subtype] relation)
together with further logically defined relations such as part_of, regulated_by
36
![Page 31: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/31.jpg)
Basic Formal Ontology (BFO)
A simple top-level ontology to support information integration in scientific research
Serves as starting point for OBO Foundry ontologies
Domain ontologies built by downward population
38
![Page 32: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/32.jpg)
Basic Formal Ontology
http://www.ifomis.org/bfo/
Continuant Occurrent
IndependentContinuant
DependentContinuant
Organism
Life
Temperature
39
![Page 33: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/33.jpg)
Example: The Cell Ontology
![Page 34: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/34.jpg)
Continuant
IndependentContinuant
DependentContinuant
..... .....
Non-realizableDependentContinuant(quality)
Realizable DependentContinuant(function, role, disposition)
TYPES
INSTANCES
![Page 35: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/35.jpg)
depends_on
Continuant
IndependentContinuant
thing
DependentContinuant
quality
.... .....
example: temperature dependson bearer
TYPES
INSTANCES
![Page 36: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/36.jpg)
DependentContinuant
QualityRealizable Dependent
Continuant
46
Disposition Function Role
of banana, to ripen
of heart, to pump blood
of employee, to work for pay
![Page 37: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/37.jpg)
process of realization depends_on realizable
Continuant Occurrent
IndependentContinuant
bearer
Realizable DependentContinuant
disposition
.... ..... .......47
Process of realization
![Page 38: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/38.jpg)
Four distinct classificatory tasks
1. of people (patients, carriers, …)
2. of diseases (cases, instances, problems, …)
3. of courses of disease (symptoms, treatments…)
4. of representations (records, observations, data, diagnoses…)
ICD confuses 1. & 2.
Most standard terminologies confuse 2. and 4
51
![Page 39: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/39.jpg)
Four distinct BFO categories
1. person (patient, carrier, …) – independent continuant
2. disease (case, instance, problem, …) – specifically dependent continuant
3. course of disease (symptom, treatment…)– occurrent
4. representation (record, datum, diagnosis…)– generically dependent continuant
52
![Page 40: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/40.jpg)
Four distinct BFO categories
1. people (patients, carriers, …) – independent continuants
2. disease (case, instance, problem, condition …) – disposition
3. course of disease (symptom, episode, outbreak …)– realization of dispositions
4. representations (records, data, diagnoses…)– generically dependent continuants
53
![Page 41: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/41.jpg)
Big Picture (Ontology for General Medical Science)
55
![Page 42: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/42.jpg)
Elucidation of Primitive Terms
‘extended organism’ = the organism and all the material entities located within it
‘bodily feature’ = either a physical part of the extended organism, a bodily quality, or a bodily process.
56
![Page 43: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/43.jpg)
Elucidation of Primitive Terms
clinically abnormal - some bodily feature that (1) is not part of the life plan for an organism of the
relevant type (unlike loss of milk teeth, aging or pregnancy),
(2) is causally linked to an elevated risk either of pain or other feelings of illness, or of death or dysfunction, and
(3) is such that the elevated risk exceeds a certain threshold level.*
*Compare: baldness
57
![Page 44: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/44.jpg)
DisorderA material entity (fiat object part) which is clinically abnormal and part of an extended organism
Compare:
Downtown Santa Barbara
Mount Everest
Peter Hucklenbroich’s pate
58
![Page 45: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/45.jpg)
Definitions - Foundational Terms
Pathological Process =def. – A bodily process that is clinically abnormal.
Disease =def. – A disposition (i) to undergo pathological processes that (ii) exists in an organism because of one or more disorders in that organism.
60
![Page 47: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/47.jpg)
Big Picture (Ontology for General Medical Science)
62
![Page 49: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/49.jpg)
Disease Course=Def. The sum of processes through which a given disease instance is realized.
65
![Page 50: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/50.jpg)
independentcontinuant
dependentcontinuant
disposition
diseaseorganism
John John’s disease
occurrent
process
course of disease
course of John’s disease
TY
PES
INS
TA
NC
ES
![Page 51: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/51.jpg)
coronary heart disease
John’s coronary heart disease
67
CHD in phase of asymptomatic
(‘silent’) infarction
CHD in phase of early lesions
and small fibrous plaques
stable angina
CHD in phase of surface
disruption of plaque
unstable angina
instantiates at t1
instantiates at t2
instantiates at t3
instantiates at t4
instantiates at t5
in nature, no sharp boundaries here
![Page 52: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/52.jpg)
human
John
68
embryo fetus adultneonate infant child
instantiates at t1
instantiates at t2
instantiates at t3
instantiates at t4
instantiates at t5
instantiates at t6
in nature, no sharp boundaries here
![Page 53: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/53.jpg)
A disease is a disposition
etiological process
produces
disorder
bears
disposition
realized_in
pathological process
produces
abnormal bodily features
recognized_as
signs & symptomsinterpretive process
produces
diagnosis
used_in71
![Page 54: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/54.jpg)
Cirrhosis - environmental exposure Etiological process - phenobarbitol-
induced hepatic cell death produces
Disorder - necrotic liver bears
Disposition (disease) - cirrhosis realized_in
Pathological process - abnormal tissue repair with cell proliferation and fibrosis that exceed a certain threshold; hypoxia-induced cell death produces
Abnormal bodily features recognized_as
Symptoms - fatigue, anorexia Signs - jaundice, splenomegaly
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - rule out cirrhosis suggests
Laboratory tests produces
Test results - elevated liver enzymes in serum used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease cirrhosis
72
![Page 55: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/55.jpg)
Influenza - infectious Etiological process - infection of
airway epithelial cells with influenza virus produces
Disorder - viable cells with influenza virus bears
Disposition (disease) - flu realized_in
Pathological process - acute inflammation produces
Abnormal bodily features recognized_as
Symptoms - weakness, dizziness Signs - fever
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - rule out influenza suggests
Laboratory tests produces
Test results - elevated serum antibody titers used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease flu
73
![Page 56: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/56.jpg)
Huntington’s Disease - genetic Etiological process - inheritance of
>39 CAG repeats in the HTT gene produces
Disorder - chromosome 4 with abnormal mHTT bears
Disposition (disease) - Huntington’s disease realized_in
Pathological process - accumulation of mHTT protein fragments, abnormal transcription regulation, neuronal cell death in striatum produces
Abnormal bodily features recognized_as
Symptoms - anxiety, depression Signs - difficulties in speaking and
swallowing
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - rule out Huntington’s suggests
Laboratory tests produces
Test results - molecular detection of the HTT gene with >39CAG repeats used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease Huntington’s disease
74
![Page 57: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/57.jpg)
Dispositions and Predispositions
Some dispositions are predispositions to other dispositions.
75
![Page 58: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/58.jpg)
HNPCC - genetic pre-disposition
Etiological process - inheritance of a mutant mismatch repair gene produces
Disorder - chromosome 3 with abnormal hMLH1 bears
Disposition (disease) - Lynch syndrome realized_in
Pathological process - abnormal repair of DNA mismatches produces
Disorder - mutations in proto-oncogenes and tumor suppressor genes with microsatellite repeats (e.g. TGF-beta R2) bears
Disposition (disease) - non-polyposis colon cancer realized in
Symptoms (including pain)
76
![Page 59: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/59.jpg)
Arterial AneurysmDisposition – atherosclerosis
realized inPathological process – fatty material collects within the walls of arteries
producesDisorder – artery with weakened wall
bearsDisposition – of artery to become distended
realized_inPathological process – process of distending
producesDisorder – arterial aneurysm
bearsDisposition – of artery to rupture
realized inPathological process – (catastrophic event) of rupturing
producesDisorder – ruptured artery, arterial system with dangerously low blood pressure
bearsDisposition – circulatory failure
realized inPathological process – exsanguination, failure of homeostasis
producesDeath
77
![Page 60: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/60.jpg)
Systemic arterial hypertension Etiological process – abnormal
reabsorption of NaCl by the kidney produces
Disorder – abnormally large scattered molecular aggregate of salt in the blood bears
Disposition (disease) - hypertension realized_in
Pathological process – exertion of abnormal pressure against arterial wall produces
Abnormal bodily features recognized_as
Symptoms - Signs – elevated blood pressure
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - rule out hypertension suggests
Laboratory tests produces
Test results - used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease hypertension
82
![Page 61: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/61.jpg)
Type 2 Diabetes Mellitus Etiological process –
produces Disorder – abnormal pancreatic beta
cells and abnormal muscle/fat cells bears
Disposition (disease) – diabetes mellitus realized_in
Pathological processes – diminished insulin production , diminished muscle/fat uptake of glucose produces
Abnormal bodily features recognized_as
Symptoms – polydipsia, polyuria, polyphagia, blurred vision
Signs – elevated blood glucose and hemoglobin A1c
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - rule out diabetes mellitus suggests
Laboratory tests – fasting serum blood glucose, oral glucose challenge test, and/or blood hemoglobin A1c produces
Test results - used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease type 2 diabetes mellitus
83
![Page 62: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/62.jpg)
Type 1 hypersensitivity to penicillin Etiological process – sensitizing of mast
cells and basophils during exposure to penicillin-class substance produces
Disorder – mast cells and basophils with epitope-specific IgE bound to Fc epsilon receptor I bears
Disposition (disease) – type I hypersensitivity realized_in
Pathological process – type I hypersensitivity reaction produces
Abnormal bodily features recognized_as
Symptoms – pruritis, shortness of breath Signs – rash, urticaria, anaphylaxis
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - suggests
Laboratory tests – produces
Test results – occasionally, skin testing used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease type 1 hypersensitivity to penicillin
84
![Page 63: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/63.jpg)
Early Onset Alzheimer’s Disease
Disorder – mutations in APP, PSEN1 and PSEN2bears
Disposition – impaired APP processingrealized in
Pathological process – accumulation of intra- and extracellular protein in the brainproduces
Disorder – amyloid plaque and neurofibrillary tanglesbearsDisposition – of neurons to dierealized in Pathological process – neuronal loss
producesDisorder – cognitive brain regions damaged and reduced in size
bearsDisposition (disease) – Alzheimer’s dementia
realized inSymptoms – episodic memory loss and other cognitive domain impairment
85
![Page 64: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/64.jpg)
Arterial Aneurysm• Disposition – atherosclerosis
– realized in• Pathological process – fatty material collects within the walls of arteries
– produces• Disorder – artery with weakened wall
– bears• Disposition – of artery to become distended
– realized_in• Pathological process – process of distending
– produces• Disorder – arterial aneurysm
– bears• Disposition – of artery to rupture
– realized in• Pathological process – (catastrophic event) of rupturing
– produces• Disorder – ruptured artery, arterial system with dangerously low blood pressure
– bears• Disposition – circulatory failure
– realized in• Pathological process – exsanguination, failure of homeostasis
– produces• Death
86
![Page 65: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/65.jpg)
Hemorrhagic stroke• Disorder – cerebral arterial aneurysm
– bears• Disposition – of weakened artery to rupture
– realized in• Pathological process – rupturing of weakened blood vessel
– produces• Disorder – Intraparenchymal cerebral hemorrhage
– bears• Disposition (disease) – to increased intra-cranial pressure
– realized in• Pathological process – increasing intra-cranial pressure, compression of brain
structures– produces
• Disorder – Cerebral ischemia, Cerebral neuronal death– bears
• Disposition (disease) – stroke– realized in
• Symptoms – weakness/paralysis, loss of sensation, etc
87
![Page 66: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/66.jpg)
88
Only something like the disposition theory enables us to explain why a fracture is not a disease
PETER HUCKLENBROICH−Radius fracture loco classico “ is a disease”
Advantages of the Disposition Theory
![Page 67: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/67.jpg)
89
PETER HUCKLENBROICH
A disease entity is a set of possible alternative courses
x has disease entity D ≡ (x has course D1) or (x has course D2) or … or (x has course Dn)
Only something like the disposition theory can allow us to determine what does and what does not belong to this list.
![Page 68: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/68.jpg)
90
Think of all the different temporal extents of the disease courses association with any given disease
• for those who die in an accident 5 seconds after catching the disease
• for those who have no treatment
• for those who have truly excellent treatment
• …
![Page 69: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/69.jpg)
91
Think of all the different combination cases:
of diseases with other diseases of diseases with complicationsof diseases at different stages of lifeof diseases with different environments
in igloosin Ost-Thüringenin sub-Saharan Africain space-ships…
![Page 70: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/70.jpg)
92
Think of all the different types of patient:
smokernon-smokerbanana-leaf-smokerAm-Sonntag-bei-Mutti-EsserAspirin-vor-dem-Schlafen-Gehen-NehmerAuf-dem-Schiessplatz-Ohrstöpsel-TrägerAuf-Weihnachtsmarkt-Lebkuchenherz-KäuferAuto-in-Waschstrasse-Abschliesser
![Page 71: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/71.jpg)
93
![Page 72: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/72.jpg)
human
John
94
embryo fetus adultneonate infant child
instantiates at t1
instantiates at t2
instantiates at t3
instantiates at t4
instantiates at t5
instantiates at t6
in nature, no sharp boundaries here
![Page 73: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/73.jpg)
portion of water
this portion of H20
95
portion of ice
portion of liquid water
portion of gas
instantiates at t1
instantiates at t2
instantiates at t3
Phrase transitions
![Page 74: Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease Berlin, March 23, 2012 1.](https://reader038.fdocuments.us/reader038/viewer/2022110209/56649e0f5503460f94afa6f8/html5/thumbnails/74.jpg)
temperature
John’s temperature
96
37ºC 37.1ºC 37.5ºC37.2ºC 37.3ºC 37.4ºC
instantiates at t1
instantiates at t2
instantiates at t3
instantiates at t4
instantiates at t5
instantiates at t6
in nature, no sharp boundaries here
in nature, no sharp boundaries here