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preAddPathRCKM⇔ (2.01)

∃RefinedClinicalKnowledgeModel0;rckmPath! :decisionPathRCKM• [def.preAddPathRCKM] (2.02)

AddPathRCKM

∃RefinedClinicalKnowledgeModel0;rckmPath! :decisionPathRCKM• [def.AddPathRCKM] (2.03)

RCKM6=∅⇒head(domdppm?) =rootRCKM∧ (2.04)

∀pos:N|pos∈domrefinements?•pos>1∧

pos≤(#(domdppm?) +#(randppm?))∧ (2.05)

ran(domrckmPath!)⊂randecisionPathConditionRCKM∧ (2.06)

ran(ranrckmPath!)⊂ranConclusionRCKM∧ (2.07) (ran(ranrckmPath!)∩randecisionPathConditionRCKM)⊂

randecisionPathConditionRCKM∧ (2.08)

0≤decPathRCKMAccuracy(rckmPath!)≤100∧ (2.09)

head(domrckmPath!)/∈ranConclusionRCKM∩randecisionPathConditionRCKM∧ (2.10)

∃dp:decisionPathRCKM|dp∈RCKM•

domrckmPath!=domdp\last(domdp)⇒last(domdp) =ranrckmPath!∧ (2.11)

domrckmPath!=∃pckm:decisionPathCKM|pckm∈CKM•

dom(ppm?)∪dompckm∧ (2.12)

ranrckmPaht!=randppm?∧ (2.13)

∀r:RefinedTreatmentPlan|r∈refinements?•

rckmPath!=a/h{tp:TreatmentPlan•(1 . . domr,tp)}domrckmPath!, ranr,

{tp:TreatmentPlan•(domr+1 . . #(domrckmPath!),tp)}domrckmPath!i ∧ (2.14)

decisionPathRCKM0=decisionPathRCKM∪ {domrckmPath!7→ranrckmPath!} ∧ (2.15)

decisionPathConditionRCKM0=decisionPathConditionRCKM∪domrckmPath!∧ (2.16)

refinedTPlan0=refinedTPlan∪refinements?∧ (2.17)

refinementsDecPath0=refinementsDecPath∪ {refinements?7→dppm?} ∧ (2.18)

ConclusionRCKM0=ConclusionRCKM∪ranrckmPath!∧ (2.19)

decPathRCKMAccuracy0=decPathRCKMAccuracy∪

{rckmPath!7→decPathRCKMAccuracy(rckmPath!)} ∧ (2.20)

accuracyRCKM0=accuracyRCKM×#RCKM+decPathRCKMAccuracy

0(rckmPath!)

#RCKM+1 ∧ (2.21)

#RCKM0=#RCKM+1∧ (2.22)

evidences0=evidences∪decPathEvidences(dppm?)∧ (2.23)

decPathRCKMEvidences0=decPathRCKMEvidences∪

{rckmPath!7→decPathEvidences(dppm?)} ∧ (2.24)

RCKM0=RCKM⊕ {domrckmPath!7→ranrckmPath!} ∧ (2.25)

refinedCKM0=refinedCKM⊕ {rckmPath!7→CKM} ∧ (2.26)

rootRCKM0=rootRCKM=head(domdppm? (2.27))

∃rckmPath! :decisionPathRCKM; [def.RefinedClinicalKnowledgeModel0] (2.28)

decisionPathConditionRCKM0:FConditionKMs; (2.29)

ConclusionRCKM0:FTreatmentPlan; (2.30)

decisionPathRCKM0:ConditionKMs7→TreatmentPlan; (2.31)

decPathRCKMAccuracy0:decisionPathRCKM0 →accuracy; (2.32)

evidences0:FEvidences; (2.33)

decPathRCKMEvidences0:decisionPathRCKM0 7→Evidences; (2.34)

refinedTPlan0:FRefinedTreatmentPlan; (2.35)

RCKM0:FdecisionPathRCKM; (2.36)

refinedCKM0:decisionPathRCKM0 →CKM; (2.37)

refinementsDecPath0:RefinedTreatmentPlandecisionPath; (2.38)

rootRCKM0: seqCondition; (2.39)

accuracyRCKM0:F Z; (2.40)

refinedCKMsAccuracy0:RCKM0 →accuracy• (2.41) (1)..decisionPathConditionRCKM0=domdecisionPathRCKM0 ∧ (2.42)

(2)..ConclusionRCKM0=randecisionPathRCKM0 ∧ (2.43) (3)..(ranConclusionRCKM0 ∩randecisionPathConditionRCKM0)⊂randecisionPathConditionRCKM0 ∧ (2.44) (4)..head(decisionPathConditionRCKM0)/ranConclusionRCKM0 ∩randecisionPathConditionRCKM0 ∧ (2.45)

(5)..evidences0=randecPathRCKMEvidences0 ∧ (2.46)

(6)..refinedTPlan0=domrefinementsDecPath0 ∧ (2.47)

Supplementary Appendix B. Simplification of primed statements using logical proofs 814

This section describes the detailed steps used to prove the primed statements in Proof2(line2.42 to 815

2.54). The primed statements are evolved using fundamental laws of set theory and deduction rules to 816

obtain the simplified form. All proofs (Proof5-15) are straightforward and instructions are provided for 817

each logical statement. 818

We introduce the necessary definitions (if required) before each proof in order to clarify the logical steps 819

in the corresponding and subsequent proofs. Proof3provides the simplification of the first prime statement 820

in PProof2(line2.42), which is concluded to the simplified statement of the R-CKM model ((Axiom3: line 821

11). In addition to the one-point rule (Definition2), the following basic definitions (Definitions4,5) are used 822

to deduce the final conclusion. 823

Proof4simplifies the primed statement in Proof2(line2.43) to the refined statement of the R-CKM 824

model (Axiom 3: line 12). Using the one-point rule (line 4.02), set subtraction, and ran properties 825

(line4.03-4.05), the proof is easily concluded. Theranproperty for the union is defined as follows. 826

Continued.. 1from Proof2

(7)..0accuracyRCKM0100 (2.48)

(8)..RCKM0=domrefinedCKM0 (2.49)

(9)..dp:decisionPathRCKM0|dpRCKM0

head(domdp)∈/ranConclusionRCKM0randecisionPathConditionRCKM0 (2.50)

(10)..dp:decisionPathRCKM0o

9dp1:decisionPathRCKM

0|dp,dp1RCKM0

last(domdp) =randp1⇔domdp1=domdp\last(domdp)∧ (2.51) (11)..accuracyRCKM0= (

letpathsAcc=={pathsAcc:Z|RCKM0 6=∅∧

(∀dp:decisionPathRCKM0|dpRCKM0pathsAcc=

decPathRCKMAccuracy0(dp) +pathsAcc)})/#RCKM0 (2.52)

(12)..p

rckm:decisionPathRCKM0|prckm∈RCKM0•

∃ppm:decisionPath,pckm:decisionPathCKM|

ppm∈PM∧pckm∈CKM•domprckm=domppm∪dompckm∧ (2.53)

(13)..RCKM6=rootRCKM0=rootRCKM ( 2.54)

RCKM6=∅⇒head(domdppm?) =rootRCKM∧ (2.55) ∀pos:N|pos∈domrefinements?•pos>1∧

pos≤(#(domdppm?) +#(randppm?))∧ (2.56)

ran(domrckmPath!)⊂randecisionPathConditionRCKM∧ (2.57)

ran(ranrckmPath!)⊂ranConclusionRCKM∧ (2.58) (ran(ranrckmPath!)∩randecisionPathConditionRCKM)⊂

randecisionPathConditionRCKM∧ (2.59)

0≤decPathRCKMAccuracy(rckmPath!)≤100∧ (2.60)

head(domrckmPath!)∈/ranConclusionRCKM∩randecisionPathConditionRCKM∧ (2.61) ∃dp:decisionPathRCKM|dp∈RCKM•

domrckmPath!=domdp\last(domdp)⇒last(domdp) =ranrckmPath!∧ (2.62)

domrckmPath!=∃pckm:decisionPathCKM|pckm∈CKM•

dom(ppm?)∪dompckm∧ (2.63)

ranrckmPaht!=randppm?∧ (2.64)

∀r:RefinedTreatmentPlan|r∈refinements?•

rckmPath!=a/h{tp:TreatmentPlan•(1 . . domr,tp)}domrckmPath!, ranr,

{tp:TreatmentPlan•(domr+1 . . #(domrckmPath!),tp)}domrckmPath!i ∧(2.65)

decisionPathRCKM0=decisionPathRCKM∪ {domrckmPath!7→ranrckmPath!} ∧ (2.66)

decisionPathConditionRCKM0=decisionPathConditionRCKM

domrckmPath!∧ (2.67)

refinedTPlan0=refinedTPlanrefinements? (2.68) refinementsDecPath0=refinementsDecPath∪ {refinements?7→dppm?} ∧ (2.69) ConclusionRCKM0=ConclusionRCKMranrckmPath! (2.70) decPathRCKMAccuracy0=decPathRCKMAccuracy

{rckmPath!7→decPathRCKMAccuracy(rckmPath!)} ∧ (2.71)

accuracyRCKM0=accuracyRCKM×#RCKM+decPathRCKMAccuracy0(rckmPath!)

#RCKM+1 ∧ (2.72)

#RCKM0=#RCKM+1 (2.73)

evidences0=evidencesdecPathEvidences(dppm?) (2.74) decPathRCKMEvidences0=decPathRCKMEvidences

{rckmPath!7→decPathEvidences(dppm?)} ∧ (2.75)

RCKM0=RCKM⊕ {domrckmPath!7→ranrckmPath!} ∧ (2.76) refinedCKM0=refinedCKM⊕ {rckmPath!7→CKM} ∧ (2.77) rootRCKM0=rootRCKM=head(domdppm?) (2.78)

Definition4:For any two functions f and g, the dom property for the union is defined as follows;

dom(f∪g)⇔domf∪domg

Definition 4: domoverunion

Definition5:For any two sets a and b, the set subtraction is formally defined as follows; a\b={x∈a|x/∈b}

Definition 5: Set subtraction

Definition6:For any two functions f and g, the ran property for the union is defined as follows;

ran(f∪g)⇔ranf∪rang

Proof5simplifies the primed statement in Proof2(line2.44) using the one-point rule (line5.02), the 827

definition of range (line5.03 using Definition6), and other laws and principles of set theory, which are 828

described in the following definitions. 829

Definition7:For any two sets a and b, the following property holds; a∪b=a⇔b⊂a

Definition 7: Union Properties

Definition8:Set intersection is distributive over A set union. For sets r, s, and t, the set intersection distribution over a union set can be defined as follows;

r∩(s∪t) = (r∩s)∪(r∩t)

Definition 8: Set intersection distribution law over union

Definition9:For sets a, b, and c, the following definition holds; a∪b⊂c⇒(a⊂c∧b⊂c)

Definition 9: Set union and proper subset

Using the one-point rule (line 6.01) and definitions of basic set theory (lines 6.02 -6.04), Proof 6

830

concludes the primed statement in Proof2(line2.45) into the R-CKM model (Axiom3: line 14). 831

Proof7concludes the primed statement in Proof2(line2.46) into the R-CKM model (Axiom3: line 15) 832

using the one-point rule (line7.02) and definitions of basic set theory (lines7.03 -7.05). 833

Using the one-point rule (line 8.02) and definitions of basic set theory (lines 8.03 -8.05), Proof 8

834

concludes the primed statement in Proof2(line2.47) into the R-CKM model (Axiom3: line 16). 835

Proof9concludes the primed statement in Proof2(line2.48) into the R-CKM model (Schema3: line 8). 836

This proof is straightforward and its conclusion is reached by using the one-point rule (line9.02,9.09) and 837

solving the inequalities with fundamental mathematics. The proof is logically decomposed into two parts 838

(lines9.03-9.07 and lines9.08-9.11). Each part is proven separately and the final statement is concluded 839

(line9.12). 840

The remaining proofs (Proof 10-Proof 15) use the same pattern of logical proofs to simplify the 841

remaining primed statements of Proof2(line2.49-line 2.54). Each step in the proofs is provided with 842

instructive definitions, and necessary definitions are included where explanation is required. 843

Definition10:The union (∪) of two functions is not always a function. However,⊕is the same as a union but ensures that combinations of the two functions are also a function. For two functions f and g,⊕is defined as follows:

f⊕g= (domg−Cf)∪g

For functions f and g, the dom property for⊕is defined as follows;

dom(f⊕g)⇔ domf⊕domg

Definition 10: domproperty over⊕

Definition11:Modus ponens, or implication elimination, is a simple argument form and rule inference in logic. For predicates p and q, the modus ponens can be formally represented as follows;

p⇒q,q`p

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