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Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale “Amedeo Avogadro”, Via Bellini 25\g, 15100 Alessandria, Italy [email protected] Aberdeen, June 4 th , 2008

Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

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Page 1: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Applying formal methods to clinical guidelines: the case of temporal information

Paolo TerenzianiDipartimento di Informatica,

Univ. del Piemonte Orientale “Amedeo Avogadro”, Via Bellini 25\g, 15100 Alessandria, Italy

[email protected]

­

­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­

­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­

Aberdeen,­June­4th,­2008

Page 2: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

My­favourite­research­topic:­Dealing­with­time-related­phenomena

­­­­­­­­­­­­­­­­Knowl.­Repr.

­­­­­­­­­­­­­­­­­Constraints­­­­­­­­­­­­­­­­­Periodicity

TDB­Semantics­­­­­­­­­­­­Constraints­DB­­­­­­­­­

Periodicity­DB­­­­­­­­­­­

­­­­­­­­­­­­­­­­­Medical­Info.­­­­­­­­­­­­­­­­­­­­­­­­­­­­­

TIME

Page 3: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Overview of the presentation

•­ experience­in­the­GL­context:­the­GLARE­project­(sketch)

• temporal­information­in­clinical­records­­temporal­databases­

•­ temporal­information­in­the­guidelines­­reasoning­about­temporal­constraints

•­ conclusions

Page 4: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

GLARE(GuideLine­Acquisition­Representation­and­

Execution)

- Joint­project­(started­in­1997):Dept.­Comp.­Sci.,­Univ.­Alessandria­(It):­P.­Terenziani,­S.Montani,­A.BottrighiDept.­Comp.­Sci.,­Univ.­Torino­(It):­L.Anselma,G.CorrendoAz.­Osp.­S.­Giovanni­Battista,­Torino­(It):­G.Molino,­M.TorchioKoinè­Sistemi­S.p.A,­Torino­(It)­(from­2005)

- Domain independent­(e.g.,­bladder­cancer,­reflux­esophagitis,­heart­failure,­ichemic­

stroke)

- Phisician-oriented & User-friendly

Page 5: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

GLARE Representation Formalism

In­GLARE,­a­clinical­guideline­is­a­hierarchical­graphs­of­actions

Page 6: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

GLARE: Architecture of the KERNEL

Clinical­DB

Pharmac.­DB

Resource­DB

ICD­DB

ExpertPhysician

AcquisitionInterface

Guidelines­DB

Knowledge­Manager

UserPhysician

ExecutionInterface

Guidelines­Instantiation­DB

PatientDB

ExecutionModule

Page 7: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

GLARE: Architecture of the system

GLARE­KERNEL

Decision-MakingModule

Temporal­ReasoningModule

UpdateModule

ContextualizationModule

Model-CheckingModule

SPIN

Page 8: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Overview of the presentation

•­ experience­in­the­GL­context:­the­GLARE­project­(sketch)­

• temporal information in clinical records temporal databases (TDBs)

•­ temporal­information­in­the­guidelines­­reasoning­about­temporal­constraints

• conclusions

Page 9: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Coping­with­temporal­information­in­patients’­records:­the­need­for­Temporal­Databases

(1) Need­for­coping­with­temporal­data­(both­VT­and­TT)

(2) Just­adding­1­(or­2,­or­4)­temporal­attributes­(and­maybe­some­ad-hoc­procedures)­does­not­work!

(3) First,­a­rigorous­semantic­framework­is­needed,­to­give­formal­specification­to­the­implementation.­Properties:­clearness,­expressiveness,­upward­compatibiliy.­­Ex.­BCDM

(4) Second,­the­implementation­must­be­proven­to­respect­the­semantics.­Core­issue­here:­efficient­(1-NF)­

implementations­hardly­grant­uniqueness­of­ representation.­Ex­TSQL2

(5) Other­issues­(my­work­in­the­area)

Page 10: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

(1)­Need­for­coping­with­temporal­data­in­patients’­clinical­records

The­time­when­patients’­symptoms­hold,­laboratory­examinations­and­clinical­actions­are­performed,­etc.­are­core­pieces­of­information­­valid­time

The­time­when­data­are­inserted\deleted­into­the­DB­is­important­(e.g.,­justification­of­actions,­legal­purposes)­­transaction­time

Ex.­Lab­test­X­has­been­executed­on­Jan­1st­,­2008,­and­results­have­been­inserted­in­the­patient’s­clinical­record­on­­Jan­3rd

NOTICE:­major­problems­even­with­valid­time­alone!

Page 11: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Coping­with­temporal­information­in­patients’­records:­the­need­for­Temporal­Databases

(1) Need­for­coping­with­temporal­data­(both­VT­and­TT)

(2) Just­adding­1­(or­2,­or­4)­temporal­attributes­(and­maybe­some­ad-hoc­procedures)­does­not­work!

(3) First,­a­rigorous­semantic­framework­is­needed,­to­give­formal­specification­to­the­implementation.­Properties:­clearness,­expressiveness,­upward­compatibiliy.­­Ex.­BCDM

(4) Second,­the­implementation­must­be­proven­to­respect­the­semantics.­Core­issue­here:­efficient­(1-NF)­

implementations­hardly­grant­uniqueness­of­ representation.­Ex­TSQL2

(5) Other­issues­(my­work­in­the­area)

Page 12: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

Example­1.­Projection­(and­temporal­coalescing)

Name Salary Title VT_start VT_end

Andrea 60000 Ass.­Provost 1/1/1993 30/5/1993

Andrea 70000 Ass.­Provost 1/6/1993 30/9/1993

Andrea 70000 Provost 1/10/1993 31/1/1994

Andrea 70000 Professor 1/2/1994 31/12/1994

Question:­salary­history­of­Andrea

“Intuitive”­SQL­query:SELECT­Salary,VT_start,VT_endFROM­EmployeeWHERE­Name=“Andrea”

Page 13: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

Result­obtained: Salary VT_start VT_end

60000 1/1/1993 30/5/1993

70000 1/6/1993 30/9/1993

70000 1/10/1993 31/1/1994

70000 1/2/1994 31/12/1994

Desired­result: Salary VT_start VT_end

60000 1/1/1993 30/5/1993

70000 1/6/1993 31/12/1994

Page 14: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

How­to­get­the­desired­result­using­SQL92:

CREATE­­TABLE­Temp(Salary,­VT_start,VT_end)AS­ SELECT­Salary,­VT_start,­VT_end

FROM­EmployeeWHERE­Name­=­“Andrea”;

RepeatUPDATE­Temp­T1SET­(T1.VT_end)=SELECT­MAX(T2.VT_end)WHERE­ T1.Salary=T2.Salary­AND­T1.VT_start­<­T2.VT_Start­AND­

T1.VT_end­>=­T2.VT_start­AND­T1.VT_end­<­T2.VT_endWHERE­EXISTS­ (SELECT­*

FROM­Temp­AS­T2WHERE­ T1.Salary=T2.Salary­AND­T1.VT_start­<­T2.VT_Start­

AND­­T1.VT_end­>=­T2.VT_start­AND­T1.VT_end­<­T2.VT_end)

Until­no­tuples­updated

Page 15: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

How­to­get­the­desired­result­using­SQL92­(continues!):

DELETE­FROM­Temp­T1WHERE­EXISTS (SELECT­*

FROM­Temp­AS­T2WHERE­T1.Salary­=­T2.Salary­AND­((T1.VT_start­>­T2.VT_Start)­AND­(T1.VT_end­<=­T2.VT_end))­OR­((T1.VT_start­>=­T2.VT_Start)­AND­(T1.VT_end­<­T2.VT_end))­

Page 16: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

Underlying­semantic­phenomenon:

Projection­on­temporal­relations­involves­temporal­coalescing­about­value­equivalent­tuples

When­it­occurs­(SQL):

Whenever­a­proper­subset­of­the­attributes­of­the­relations­is­chosen­in­the­SELECT­part­of­the­query

Page 17: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

How­to­get­the­desired­result­using­a­Temporal­DB­(ex.­TSQL2)

SELECT­SalaryFROM­EmployeeWHERE­Name­=­“Andrea”

Page 18: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

Example­2.­Join­(and­temporal­intersection)

Name Salary VT_start VT_end

Andrea 60000 1/1/1993 30/5/1993

Andrea 70000 1/6/1993 31/12/1994

Employee1

Name Title VT_start VT_end

Andrea Ass.­Provost 1/1/1993 30/9/1993

Andrea Provost 1/10/1993 31/1/1994

Andrea Professor 1/2/1994 31/12/1994

Employee2

Query:­“combined”­history­of­both­Andrea’s­salary­and­title

Page 19: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

“Intuitive”­SQL­query:SELECT­Salary,­Title,­Emp1.VT_start,­Emp1.VT_end

­Emp2.VT_start,­Emp2.VT_end­FROM­ Employee1,­Employee2WHERE­ Employee1.Name=“Andrea”­AND

­ Employee1.Name=“Andrea”­

Page 20: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

Result­obtained:

Salary Emp1.VT_start

Emp1.VT_end

Title Emp2.VT_start

Emp2.VT_end

60000 1/1/1993 30/5/1993 Ass.­Provost 1/1/1993 30/9/1993

60000 1/1/1993 30/5/1993 Provost 1/10/1993 31/1/1994

60000 1/1/1993 30/5/1993 Professor 1/2/1994 31/12/1994

70000 1/6/1993 31/12/1994 Ass.­Provost 1/1/1993 30/9/1993

70000 1/6/1993 31/12/1994 Provost 1/10/1993 31/1/1994

70000 1/6/1993 31/12/1994 Professor 1/2/1994 31/12/1994

Page 21: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

Result­desired:

Salary Title VT_start VT_end

60000 Ass.­Provost 1/1/1993 30/5/1993

70000 Ass.­Provost 1/6/1993 30/9/1993

70000 Provost 1/10/1993 31/1/1994

70000 Professor 1/2/1994 31/12/1994

Page 22: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

How­to­get­the­desired­result­using­SQL92:SELECT­Employee1.Name,Salary,Dept,Employee1.VT_start,Employee1.VT_endFROM­Employee1,­Employee2WHERE­Employee1.Name=Employee2.Name­AND­Employee2.VT_start­<=­Employee1.VT_start­AND­Employee1.VT_end­<­Employee2.VT_endUNIONSELECT­Employee1.Name,Salary,Dept,Employee1.VT_start,Employee2.VT_endFROM­Employee1,­Employee2WHERE­Employee1.Name=Employee2.Name­AND­Employee1.VT_start­>=­Employee2.VT_start­AND­Employee2.VT_end­<­Employee1.VT_end­AND­Employye1.VT_start­<­Employee2.VT_endUNIONSELECT­Employee1.Name,Salary,Dept,Employee2.VT_start,Employee1.VT_endFROM­Employee1,­Employee2WHERE­Employee1.Name=Employee2.Name­AND­Employee2.VT_start­>­Employee2.VT_start­AND­Employee1.VT_end­<­Employee2.VT_end­AND­Employye2.VT_start­<­Employee1.VT_endUNIONSELECT­Employee1.Name,Salary,Dept,Employee2.VT_start,Employee2.VT_endFROM­Employee1,­Employee2WHERE­Employee1.Name=Employee2.Name­AND­Employee2.VT_start­>­Employee1.VT_start­AND­Employee2.VT_end­<­Employee1.VT_end

Page 23: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

Underlying­semantic­phenomenon:

Join­(Cartesian­product)­on­temporal­relations­involves­temporal­intersection

When­it­occurs­(SQL):

Whenever­­more­than­one­relation­is­used­in­the­FROM­part­of­the­query

Note:­the­number­of­terms­in­the­SQL­union­is­2n,­where­n­is­the­number­of­relations­in­the­FROM­part

Page 24: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

How­to­get­the­desired­result­using­a­Temporal­DB­(ex.­TSQL2)

SELECT­Salary,­TitleFROM­ Employee1,­Employee2WHERE­ Employee1.Name=“Andrea”­AND

­ Employee1.Name=“Andrea”­

Page 25: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

And what about:-­ Union,­difference,­…,­nested­queries-­ Temporal­predicates-­ Primary\secondary­keys-­ Aggregate­functions-­ Integrity­constraints-­ Multiple­(user-defined!)­granularities-­ ……-­ arbitrary­combinations­of­all­the­above­issues

Until­now,­just­two­simple­examples­concerning:-­SELECT­a­subset­of­attributes­(­loop­to­do­colaescing)-­FROM­with­>1­relations­(exponential­union­to­do­intersection)

?

Page 26: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

Key­message:-­ Dealing­with­temporal­data­is­a­general­problem­in­DB’s-­ Difficult­problems­(often­“hidden”­ones)­have­to­be­faced

From­a­Software­Engeneering­point­of­view:Letting­applications­solve­the­problem­in­an­ad-hoc­way­is:-­ Both­cost­and­time­expensive-­ Likely­to­lead­to­errors­in­the­applications-­ Likely­to­make­integration­(shared­data)­between­­applications­impossible

Page 27: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Ad-hoc­approaches­are­complex­and­are­not­likely­to­work

Temporal DB: an area of research aiming at

providing once-and-forall principled and integrated solution to the problem

Page 28: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Coping­with­temporal­information­in­patients’­records:­the­need­for­Temporal­Databases

(1) Need­for­coping­with­temporal­data­(both­VT­and­TT)

(2) Just­adding­1­(or­2,­or­4)­temporal­attributes­(and­maybe­some­ad-hoc­procedures)­does­not­work!

(3) First,­a­rigorous­semantic­framework­is­needed,­to­give­formal­specification­to­the­implementation.­Properties:­clearness,­expressiveness,­upward­compatibiliy.­­Ex.­BCDM

(4) Second,­the­implementation­must­be­proven­to­respect­the­semantics.­Core­issue­here:­efficient­(1-NF)­

implementations­hardly­grant­uniqueness­of­ representation.­Ex­TSQL2

(5) Other­issues­(my­work­in­the­area)

Page 29: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM(Bitemporal­Conceptual­Data­Model)

Snodgrass & Jensen, 1995

A­unifying­“consensus” model,­capturing­the­semantics­of­most­approaches­in­the­TDB­literature

-­­ Based­on­the­relational­model,­and­tuple­timestamping-­ A­purely­semantic­model­(efficiency­issues­are­not­taken­

into­account)

Page 30: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

Temporal­Domains

-­ Time­is­linear­and­totally­ordered-­ Chronons­are­the­basic­time­unit-­ Time­domains­are­isomorphic­to­subsets­of­the­domain­­

of­Natural­numbers

DVT­=­{t1,t2,­…,­tk} (valid­time)­DTT­=­{t’1,t’2,­…,­t’h}­­{UC}­ (transaction­time)DTT­­DVT ­(bitemporal­chronons)

Page 31: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

Data

Attribute­names:­DA={A1,­A2,­…,­An}Attribute­domains­DD={D1,­D2,­…,­Dn}

Schema­of­a­bitemporal­relation:R­=­Ai1,­Ai2,­…,­Aij­T

Domain­of­a­bitemporal­relation:Di1­­Di2­­…­­Dij­­­DTT­­DVT

Tuple­of­a­relation­r(R):x­=­(a1,­a2,­…,­aj­|­tB)

Page 32: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

Example.Relation­Employee­with­Schema:­(name,salary,T)

“Andrea­was­earning­60K­at­valid­times­10,­11,­12Such­a­tuple­has­been­inserted­into­Employee­at­time­12,­and­is­current­now­(say­now=13)”

(Andrea,­60k­|­{(12,10),­(12,11),­(12,12),(13,10),­(13,11),­(13,12),­……})­

VT

TT

10

12

12 13

11

Page 33: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

Example.Relation­Employee­with­Schema:­(name,salary,T)

“Andrea­was­earning­60K­at­valid­times­10,­11,­12Such­a­tuple­has­been­inserted­into­Employee­at­time­12,­and­is­current­now­(say­now=13)”

(Andrea,­60k­|­{(12,10),­(12,11),­(12,12),(13,10),­(13,11),­(13,12),­(UC,10),­(UC,11),­(UC,12)})­

VT

TT

10

12

12 13

11

UC

Page 34: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

Bitemporal relation:­set­of­bitemporal­tuples.­Constraint:­Value­equivalent­tuples­are­not­allowed.

(Bitemporal)­DB:­set­of­(bitemporal)­relations

Page 35: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

Semantics (another viewpoint)

Name Salary T

Andrea 60K {(12,10),­(12,11),­(12,12),(13,10),­(13,11),­(13,12),­(UC,10),­(UC,11),­(UC,12)}

John 50K {(12,12),(12,­13)}

(12,10)­­{Employee(Andrea,60K)}(12,11)­­{Employee(Andrea,­60K)}(12,12)­­{Employee(Andrea,­60K),­Employee(John,50K)}(12,13)­­{Employee(John,50K)}(13,10)­­{Employee(Andrea,60K)}(13,11)­­{Employee(Andrea,­60K)}……..(UC,12)­­{Employee(Andrea,­60K)}

Page 36: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

PROPERTIES

Consistent extension (of “classical” SQL DB)A­temporal­DB­is­a­set­of­“classical”­DBs,­one­for­each­bitemporal­chronon

Uniqueness of representation(from­the­constraint­about­value­equivalent­tuples)

Page 37: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

Semantics of UCe.g.,­the­DB’s­clock­thicks­time­14

Name Salary T

Andrea 60K {(12,10),­(12,11),­(12,12),(13,10),­(13,11),(13,12),­(UC,10),­(UC,11),­(UC,12)}

John 50K {(12,12),(12,­13)}

Name Salary T

Andrea 60K {(12,10),­(12,11),­(12,12),(13,10),­(13,11),­(13,12),­(14,10), (14,11), (14,12), (UC,10),­(UC,11),­(UC,12)}

John 50K {(12,12),(12,­13)}

Page 38: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

deletion (e.g.,­at­time­15)delete(Employee,­(Andrea,60K))­

Name Salary T

Andrea 60K {(12,10),­(12,11),­(12,12),(13,10),­(13,11),­(13,12),­(14,10),­(14,11),­(14,12), (UC,10),­(UC,11),­(UC,12)}

John 50K {(12,12),(12,­13)}

Name Salary T

Andrea 60K {(12,10),­(12,11),­(12,12),(13,10),­(13,11),­(13,12),­(14,10),­(14,11),­(14,12), (UC,10),­(UC,11),­(UC,12)}

John 50K {(12,12),(12,­13)}

Page 39: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

insertion (e.g.,­at­time­16)insert(Employee,­(Andrea,60K|{12,13}))insert(Employee,­(Mary,70K|{16}))

Name Salary T

Andrea 60K {(12,10),­(12,11),­(12,12),(13,10),­(13,11),­(13,12),­(14,10),­(14,11),­(14,12), (UC,10),­(UC,11),­(UC,12)}

John 50K {(12,12),(12,­13)}

Name Salary T

Andrea 60K {(12,10),­(12,11),­(12,12),(13,10),­(13,11),­(13,12),­(14,10),­(14,11),­(14,12),­(16,12),(16,13),(UC,12),(UC,13) }

John 50K {(12,12),(12,­13)}

Mary 70K {(16,16),(UC,16)}

Page 40: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

πD(r)={z­|­∃xr (z[D]=x[D]) ∧ ∀ yr (y[D]=z[D] ⇒ y[T] z[T]) ∧ ∀ tz[T] ∃yr (y[D]=z[D] ∧ ty[T])}

Algebraic Operators(Ex. Projection)

-­ No­value-equivalent­tuple­generated(uniqueness­of­representation!)

-­ Coalescing!

Page 41: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

BCDM­algebraic­operators­are­a­consistent­extension­of­SQL’s­ones(reducibility­and­equivalence)

Algebraic OperatorsProperties

Page 42: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

Reducibility

rT ρtT­(rT)ρtT

opT­(rT)

opT op

op(ρtT­(rT))ρtT

ρtT(opT­(rT))=

Page 43: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

Equivalence

rτt τt(r)

opTop

op(r)τt

τt(op(r))=opT­(τt(r))

Page 44: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

BCDM

PROBLEM

Semantically­clear­but­…..­inefficient­(not­suitable­for­a­“direct”­implementation)

(1)­ Not­1-NF

(2)­ UC­(at­each­thick­of­the­clock,­all­current­tuples­

should­be­ updated!)

Page 45: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Coping­with­temporal­information­in­patients’­records:­the­need­for­Temporal­Databases

(1) Need­for­coping­with­temporal­data­(both­VT­and­TT)

(2) Just­adding­1­(or­2,­or­4)­temporal­attributes­(and­maybe­some­ad-hoc­procedures)­does­not­work!

(3) First,­a­rigorous­semantic­framework­is­needed,­to­give­formal­specification­to­the­implementation.­Properties:­clearness,­expressiveness,­upward­compatibiliy.­­Ex.­BCDM

(4) Second,­the­implementation­must­be­proven­to­respect­the­semantics.­Core­issue­here:­efficient­(1-NF)­

implementations­hardly­grant­uniqueness­of­ representation.­Ex­TSQL2

(5) Other­issues­(my­work­in­the­area)

Page 46: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

An­example­of­implementation:­TSQL2(Snodgrass et al., 1995)

Temporal­attribute­T­­four­temporal­attributes­(TTS,­TTE,­VTS,­VTE)

Attribute­value:­a­timestamp­or­UC

Bitemporal­tuple:­A1,….An|­TTS,­TTE,­VTS,­VTE

Bitemporal­relation:­set­of­bitemporal­tuples

Notice: to retain the expressiveness of BCDM, value-equivalent tuples need to be allowed!

Page 47: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

An­example­of­implementation:­TSQL2(Snodgrass­et­al.,­1995)

Name Salary T

Andrea 60K {(12,10),­(12,11),­(12,12),(13,10),­(13,11),­(13,12),­(UC,10),­(UC,11),­(UC,12)}

John 50K {(12,12),(12,­13)}

Name Salary TTS TTE VTS VTE

Andrea 60K 12 UC 10 12

John 50K 12 12 12 13

SEMANTICS

BCDM

TSQL2

Page 48: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

An­example­of­implementation:­TSQL2(Snodgrass­et­al.,­1995)

Efficient­implementation­(data­model):-­ 1-NF-­ UC­managed­efficiently-­ clear­semantics­(mapping­onto­BCDM)

BUT

to get efficiency, we loose the uniqueness of representation property

Page 49: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Problem:­no­uniqueness­of­representation

Name Salary T

Andrea 60K {(10,2),­(10,3),­(11,­2),(11,3),­(12,1),­(12,2),(12,3),(12,4),(13,1),(13,2),(13,3),(13,4)}

Name Salary TTS TTE VTS VTE

Andrea 60K 10 11 2 3

Andrea 60K 12 UC 1 4

Name Salary TTS TTE VTS VTE

Andrea 60K 12 UC 1 1

Andrea 60K 10 UC 2 3

Andrea 60K 12 UC 4 4

BCDM

SEMANTICSTSQL2­(a)­ TSQL2­(b)­

Example. At­time­10,­the­fact­that­Andrea­earned­60K­from­2­to­3­inserted­in­Employee.­At­time­12,­such­a­tuple­is­updated:­Andrea­earned­60K­from­1­to­4.­At­time­13,­the­tuple­is­(logically)­deleted.

Page 50: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Problem:­no­uniqueness­of­representation

VT

TT

12

12 13

3

4

10 11

TSQL2­implementation:­“covering”­rectangles

Page 51: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Problem:­no­uniqueness­of­representation

VT

TT

12

12 13

3

4

10 11

TSQL2­Representation­(a)

Name Salary TTS TTE VTS VTE

Andrea 60K 10 11 2 3

Andrea 60K 12 UC 1 4

Page 52: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Problem:­no­uniqueness­of­representation

VT

TT

12

12 13

3

4

10 11

TSQL2­Representation­(b)

Name Salary TTS TTE VTS VTE

Andrea 60K 12 UC 1 1

Andrea 60K 10 UC 2 3

Andrea 60K 12 UC 4 4

Page 53: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Problem:­no­uniqueness­of­representation

VT

TT

12

12 13

3

4

10 11

Other­TSQL2­Representations!!

Page 54: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Problem:­no­uniqueness­of­representation

Name Salary TTS TTE VTS VTE

Andrea 60K 10 11 2 3

Andrea 60K 12 UC 1 4

Name Salary TTS TTE VTS VTE

Andrea 60K 12 UC 1 1

Andrea 60K 10 UC 2 3

Andrea 60K 12 UC 4 4

Potentially,­an­enormous­problem!

e.g.,­Return­all­employees­earning­more­than­50K­for­at­most­3­consecutive­time­chronons

Name TTS TTE VTS VTE

Andrea 12 UC 1 4?

Page 55: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Problem:­no­uniqueness­of­representation

One must grant that the temporal DB implementation respects its underlying semantics, independently of the representation

DB1

DB2

op1,­…,­opkDB1’

DB2’op1,­…,­opk

Given­two­“semantically­equivalent”­temporal­DBs,­and­given­any­sequence­of­operations,­the­results­are­always­“semantic­equivalent”

Otherwise …..We cannot trust DB’s results!

Page 56: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Problem:­no­uniqueness­of­representation

Solution. Step 1. Formal definition of “semantic equivalence”

Snapshot equivalence:Informally:­two­relations­(Databases)­are­snapshot­equivalent­if­they­are­identical­at­each­bitemporal­chronon

Page 57: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Problem:­no­uniqueness­of­representation

Solution. Step 2. Definition of manipulation and algebraic operators that preserve snapshot equivalence

e.g., proofs given about TSQL2 (bitemporal) operators

rB1

rB2

opBi

opBi

opBi(rB1)

opBi(rB2)

snapshotequivalent

snapshotequivalent

Page 58: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

An­example­of­implementation:­TSQL2(Snodgrass­et­al.,­1995)

Last,­but­not­least,

An­high-level­query­and­manipulation­language­(minimal­extension­to­SQL­to­cope­with­time)­is­provided

Page 59: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

An­example­of­implementation:­TSQL2(Snodgrass­et­al.,­1995)

Other­properties­proved­for­TSQL2

(Upward­Compatibility)TSQL2­is­a­consistent­extension­of­SQL

Page 60: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Personal­consideration

In­my­opinion,­ad-hoc­approaches­are­not­likely­to-­ Recognize-­ Solve-­ Prove­the­soundness­of­the­­solutionsthe­above­problems!

Page 61: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Coping­with­temporal­information­in­patients’­records:­the­need­for­Temporal­Databases

(1) Need­for­coping­with­temporal­data­(both­VT­and­TT)

(2) Just­adding­1­(or­2,­or­4)­temporal­attributes­(and­maybe­some­ad-hoc­procedures)­does­not­work!

(3) First,­a­rigorous­semantic­framework­is­needed,­to­give­formal­specification­to­the­implementation.­Properties:­clearness,­expressiveness,­upward­compatibiliy.­­Ex.­BCDM

(4) Second,­the­implementation­must­be­proven­to­respect­the­semantics.­Core­issue­here:­efficient­(1-NF)­

implementations­hardly­grant­uniqueness­of­ representation.­Ex­TSQL2

(5) Other­issues­(my­work­in­the­area)

Page 62: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

My­past­and­current­contribution­to­the­area

-­ Treatment of temporal constraints in TDB(with­V.­Brusoni,­L.­Console,­B.­Pernici:­IEEE­Trans.­Data­and­Knowledge­Eng.,­1998)-­ Treatment of periodic data in TDB(IEEE­Trans.­Data­and­Knowledge­Eng.,­2003,­and­futher­ongoing­work­with­B.Stantic,­G.­Governatori,­A.­Sattar)-­ Treatment of telic vs atelic data in TDB(with­R.T.­Snodgrass,­IEEE­Trans.­Data­and­Knowledge­Eng.,­2004)-­ Extension to BCDM to cope with proposal\evaluation of updates (with­L.­Anselma,­A.­Bottrighi,­S.­Montani,­ongoing­work)-­ Extension to BCDM to cope with temporal indeterminacy(with­R.T.­Snodgrass,­ongoing­work)

Page 63: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Treatment­of­telic­vs­atelic­data­in­TDB­(joint­work­with­R.T.­Snodgrass)

Distinction­dates­back­to­Aristotle’s­Categories,­used­in­Linguistics,­Cognitive­Science,­and,­recently,­Artificial­Intelligence

Core­issue:Atelic­facts­(i.e.,­facts­without­a­goal­or­culmination)e.g.,­ (f1)­Andrea­earned­60K­from­10­to­11

(f2)­Andrea­earned­60K­from­12­to­12can­be­represented\evaluated­at­each­bitemporal­chronon

10­­{earn(Andrea,60K)}11­­{earn(Andrea,60K)}12­­{earn(Andrea,60K)}

­BCDM­“snapshot”­semantics­is­OK­for­atelic­facts

Page 64: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Treatment­of­telic­vs­atelic­data­in­TDB

Core­issue:Telic­facts­(i.e.,­facts­with­a­goal­or­culmination)e.g.,­ (f1)­Andrea­build­a­house­from­10­to­11

(f2)­Andrea­build­a­house­from­12­to­12cannot­­be­represented\evaluated­at­each­bitemporal­chronon

10­­{build_house(Andrea)}11­­{build_house(Andrea)}12­­{build_house(Andrea)}

­BCDM­“snapshot”­semantics­does­not­work­for­telic­facts

Page 65: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Treatment­of­telic­vs­atelic­data­in­TDB

(1) Analysis­of­the­impact­of­neglecting­the­telic\atelic­distinction­in­TDBs

(2) Solution:­(2.1) a­two-sorted­semantics- chronon-by-chronon­for­atelic­facts- interval-based­for­telic­facts

(2.2) three­sorted­data­model(2.3) three-sorted­manipulation­and­algebraic­operators(2.4) properties(2.5) high-level­query­language

Page 66: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Treatment­of­proposal\evaluation­of­updates(extension­to­BCDM)­

(joint­work­with­L.­Anselma,­A.­Bottrighi,­S.­Montani)

Needed­to­cope­with­updates­concerning­GLs!

Important­in­several­other­applications,­e.g.,­Wiki-based­vocabularies­(Citizendium)

Notice:­TT­needed­to­store­the­history­of­updates!

Main­issues:- Distinguishing­between­two­level­of­users­(proposers­and­evaluators)

- Delaying­the­effect­of­proposals- Coping­with­alternative­tuples

Page 67: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Overview of the presentation

•­ experience­in­the­GL­context:­the­GLARE­project­(sketch)

•­ temporal­information­in­clinical­records­­ temporal­databases­(TDB)

• temporal information in the guidelines reasoning about temporal constraints

• conclusions

Page 68: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Temporal­Constraints­in­Clinical­Guidelines

Temporal­constraints­are­an­intrinsic­part­of­clinical­knowledge­(e.g.,­ordering­of­the­therapeutic­actions)

Different­kinds­of­temporal­constraints,­e.g.,­

- duration­of­actions­(min­/­max)­

- qualitative­constraints­(e.g.,­before,­during)

- delays­(min­/­max)

- periodicity­constraints­on­repeated­actions

Page 69: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Temporal­Constraints­in­Clinical­Guidelinesrepetitions

The therapy for multiple mieloma is made by six cycles of 5-day treatment, each one followed by a delay of 23 days (for a total time of 24 weeks). Within each cycle of 5 days, 2 inner cycles can be distinguished: the melphalan treatment, to be provided twice a day, for each of the 5 days, and the prednisone treatment, to be provided once a day, for each of the 5 days. These two treatments must be performed in parallel.

Page 70: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Managing­Temporal­Constraint:­the­Problem

Temporal Constraints without Temporal Reasoning (constraint propagation)- are useless- clash against users’ intuitions/expectations

Both representation and inference are NEEDED

Page 71: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Managing­Temporal­Constraints:­the­Problem

Implied constraint (temporal reasoning):(1.6)­C­ends­between­30­and­60­m­after­the­start­of­A

(1.1)­the­end­of­A­is­equal­to­the­start­of­B(1.2)­the­end­of­B­is­equal­to­the­start­of­C(1.3)­the­duration­of­A­is­between­10­and­20­m(1.4)­the­duration­of­B­is­between­10­and­20­m(1.5)­the­duration­of­C­is­between­10­and­20­m

A B C10-20 10-2010-20

Correct (consistent) assertion:(1.7)­C­ends­between­30­and­50­m­after­the­start­of­A

Not correct (inconsistent) assertion:(1.8)­C­ends­more­than­70­m.­after­the­start­of­A

However: Temporal Reasoning is NEEDED in order to support such an intended semantics!

Page 72: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Managing­Temporal­Constraints:­the­Problem

DESIDERATA­for­Temporal­Reasoning­Algorithms

-­tractability­­“reasonable”­response­time­

-­correctness­­no­wrong­inferences

-­completeness­­reliable­answers

DESIDERATA­for­the­Representation­formalism

-­expressiveness­­capture­most­temporal­constraints­in­GL

TRADE-OFF!

SPECIALIZED­APPROACHES­(since­’80­in­AI­literature)

Page 73: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Digression:­Why­Completeness­is­fundamental?

Implied constraint (temporal reasoning):(1.6)­C­ends­between­30­and­60­m­after­the­start­of­A

(1.1)­the­end­of­A­is­equal­to­the­start­of­B(1.2)­the­end­of­B­is­equal­to­the­start­of­C(1.3)­the­duration­of­A­is­between­10­and­20­m(1.4)­the­duration­of­B­is­between­10­and­20­m(1.5)­the­duration­of­C­is­between­10­and­20­m

A B C10-20 10-2010-20

Suppose­that­temporal­reasoning­is­NOT complete,­so­that­(1.6)­is­not­inferred.­One­can­add­inconsistent­info,­e.g.,­C­ends­more­than­70­m.­after­the­start­of­Aand­the­system­accept­it!­ inconsistent GL!

Complete Temporal Reasoning is NEEDED in order to grant that GL is temporally consistent (executable!)

Page 74: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Temporal­Constraint­Treatment

WHEN Temporal Reasoning is useful in Guidelines?

ACQUISITION

-­ to­check­consistency­(notice:­an­inconsistent­GL­cannot­be­executed!!!)

EXECUTION

- to­compare­the­duration­of­paths,­­in­hypothetical­reasoning­­(simulation)­facilities

- to­check­that­the­time­of­execution­of­actions­on­patients­is­consistent­with­the­constraints­in­the­guideline­

- to­schedule­next­actions

Page 75: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Temporal­Representation­and­Temporal­Reasoning­for­Clinical­Guidelines

• Different­kinds­of­temporal­constraints

• No­current­approach­in­the­AI­literature­covers­all­of­them

• Our­proposal:­an­extension­of­the­“consensus”­STP­approach­[Dechter­et­al.,­91]

• Our­goal:­expressiveness­+­correct,­complete­and­tractable­inferences

Page 76: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

GLARE’s­approach­(representation)Labeled­tree­of­STPs­(STPs-tree)

Tree of STPs for the multiple mieloma chemotherapy guideline.The overall therapy (node N1) is composed by 6 cycles of 5 days plus a delay of 23 days . In each cycle (node N2), two therapies are executed in parallel: Alkeran (node N3: Sa and Ea are the starting and ending nodes), to be repeated twice a day, and Deltacorten (node N4: Sd and Ed are the starting and ending nodes), to be repeated once a day. Arcs between any two nodes X and Y in a STP (say N2) of the STP-tree are labeled by a pair [n,m] representing the minimal and maximal distance between X and Y.

Page 77: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Other­formal­approaches­to­temporal­reasoning­in­clinical­guidelines

Miksh­­et­al.- an­extension­of­STP’s­metric­contraints- attention­to­constraint­visualization

Shahar­et­al.- temporal­reasoning­oriented­towards­

temporal­abstraction­(e.g.,­persistence­phenomena)

Page 78: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Conclusions

Formal­methods­are­necessary­in­order­to­properly­cope­with­temporal­phenomena­related­to­GL­management

Temporal­information­in­patients’­records­­TDBs­needed- ­ad-hoc­solutions­are­complex,­expensive,­not­likely­to­work- a­clear­semantics­is­needed-­ an­efficient­(1-NF)­implementation­respecting­the­semantics­is­­

needed.­(semantic­equivalence­must­be­preserved,­otherwise, results cannot be trusted!)

-­ any­implementation­should­be­a­consistent­extension­of­SQL­(otherwise, previous work is lost!)

Temporal­constraints­in­GLs­­Temporal­reasoning­needed- (temporally)­inconsistent­GL­cannot­be­executed!- to­detect­which­are­the­next­candidate­actions,­and­

when­they­need­to­be­executed­

Page 79: Applying formal methods to clinical guidelines: the case of temporal information Paolo Terenziani Dipartimento di Informatica, Univ. del Piemonte Orientale

Conclusions

More­generally,­I­strongly­believe­that­formal methods are recommended\necessary in­order­to­properly­cope­with­many­other­different­phenomena­related­to­GL­management,­including

-­ Decision­support­(e.g.,­Decision­Theory)-­ Verification­(e.g.,­model-checking,­theorem­proving,­Petri­Nets)-­ Simulation­(e.g.,­Petri­Nets)-­ Formal­semantics­(Temporal­logics,­Operational­semantics,­

Mapping­techniques)-­ ………­!!!

Thanks for your attention!