2615 overriding ref conc and applying hi should use the updated refconc

src/PKSim.Core/Mappers/IndividualToIndividualBuildingBlockMapper.cs

@@ -95,6 +95,7 @@ public override IndividualBuildingBlock MapFrom(Individual individual)
          buildingBlock.Icon = individual.Icon;
 
          addOriginDataToBuildingBlock(buildingBlock, PKSimConstants.UI.DiseaseState, individual.OriginData.DiseaseState?.DisplayName);
+         individual.OriginData.DiseaseStateParameters.Each(x => addOriginDataToBuildingBlock(buildingBlock, x.Name, x));
          addOriginDataToBuildingBlock(buildingBlock, PKSimConstants.UI.Species, individual.Species?.DisplayName);
          addOriginDataToBuildingBlock(buildingBlock, PKSimConstants.UI.Gender, individual.OriginData.Gender?.DisplayName);
          addOriginDataToBuildingBlock(buildingBlock, PKSimConstants.UI.Age, individual.OriginData.Age);
@@ -124,17 +125,14 @@ private void addOriginDataToBuildingBlock(IndividualBuildingBlock buildingBlock,
          addOriginDataToBuildingBlock(buildingBlock, keyForOriginDataParameter(key, parameter), $"{parameter.Value} {parameter.Unit}");
       }
 
-      private string keyForOriginDataParameter(string key, OriginDataParameter parameter)
-      {
-         return string.IsNullOrEmpty(parameter.Name) ? key : parameter.Name;
-      }
-
       private void addOriginDataToBuildingBlock(IndividualBuildingBlock buildingBlock, string key, string value)
       {
          if (string.IsNullOrEmpty(value))
             return;
 
          buildingBlock.OriginData.Add(new ExtendedProperty<string> {Name = key, Value = value});
       }
+
+      private string keyForOriginDataParameter(string key, OriginDataParameter parameter) => string.IsNullOrEmpty(parameter.Name) ? key : parameter.Name;
    }
 }

src/PKSim.Core/Mappers/PathAndValueBuildingBlockMapper.cs

@@ -8,7 +8,6 @@
 using OSPSuite.Utility;
 using OSPSuite.Utility.Extensions;
 using PKSim.Core.Model;
-using PKSim.Core.Model.Extensions;
 using IFormulaFactory = PKSim.Core.Model.IFormulaFactory;
 
 namespace PKSim.Core.Mappers
@@ -126,10 +125,7 @@ private IFormula retrieveTemplateFormulaFromCache(IParameter parameter, TPKSimBu
 
       protected abstract IFormula TemplateFormulaFor(IParameter parameter, IFormulaCache formulaCache, TPKSimBuildingBlock pkSimBuildingBlock);
 
-      private static double getParameterValue(IParameter parameter)
-      {
-         return parameter.TryGetValue().value;
-      }
+      private static double getParameterValue(IParameter parameter) => parameter.TryGetValue().value;
 
       protected void MapAllParameters(TPKSimBuildingBlock sourcePKSimBuildingBlock, TBuildingBlock buildingBlock)
       {

src/PKSim.Core/Model/ExpressionProfile.cs

@@ -25,10 +25,12 @@ public Individual Individual
 
       public virtual Species Species => Individual?.Species;
 
+      public virtual DiseaseState DiseaseState => Individual?.OriginData?.DiseaseState;
+
       public ExpressionProfile() : base(PKSimBuildingBlockType.ExpressionProfile)
       {
       }
-      
+
       public override IReadOnlyList<T> GetAllChildren<T>()
       {
          return Individual.GetAllChildren<T>();

src/PKSim.Core/Model/IndividualFactory.cs

@@ -29,7 +29,7 @@ public class IndividualFactory : IIndividualFactory
       private readonly IReportGenerator _reportGenerator;
       private readonly IMoleculeOntogenyVariabilityUpdater _ontogenyVariabilityUpdater;
       private readonly IGenderRepository _genderRepository;
-      private readonly IDiseaseStateImplementationFactory _diseaseStateImplementationFactory;
+      private readonly IDiseaseStateImplementationRepository _diseaseStateImplementationRepository;
 
       public IndividualFactory(
          IIndividualModelTask individualModelTask,
@@ -40,7 +40,7 @@ public IndividualFactory(
          IReportGenerator reportGenerator,
          IMoleculeOntogenyVariabilityUpdater ontogenyVariabilityUpdater,
          IGenderRepository genderRepository,
-         IDiseaseStateImplementationFactory diseaseStateImplementationFactory)
+         IDiseaseStateImplementationRepository diseaseStateImplementationRepository)
       {
          _individualModelTask = individualModelTask;
          _objectBaseFactory = objectBaseFactory;
@@ -50,7 +50,7 @@ public IndividualFactory(
          _reportGenerator = reportGenerator;
          _ontogenyVariabilityUpdater = ontogenyVariabilityUpdater;
          _genderRepository = genderRepository;
-         _diseaseStateImplementationFactory = diseaseStateImplementationFactory;
+         _diseaseStateImplementationRepository = diseaseStateImplementationRepository;
       }
 
       public Individual CreateAndOptimizeFor(OriginData originData, int? seed = null)
@@ -63,7 +63,7 @@ public Individual CreateAndOptimizeFor(OriginData originData, int? seed = null)
          _createIndividualAlgorithm.Optimize(individual);
 
          //Apply disease states if required
-         var diseaseStateImplementation = _diseaseStateImplementationFactory.CreateFor(individual);
+         var diseaseStateImplementation = _diseaseStateImplementationRepository.FindFor(individual);
          diseaseStateImplementation.ApplyTo(individual);
 
          validate(individual);
@@ -138,7 +138,7 @@ private void validate(Individual individual)
                throw new CannotCreateIndividualWithConstraintsException(_reportGenerator.StringReportFor(individual.OriginData));
 
             //Apply disease states if required
-            var diseaseStateImplementation = _diseaseStateImplementationFactory.CreateFor(individual);
+            var diseaseStateImplementation = _diseaseStateImplementationRepository.FindFor(individual);
             //This will throw if not valid
             diseaseStateImplementation.Validate(individual.OriginData);
          }

src/PKSim.Core/Model/RandomPopulationFactory.cs

@@ -47,7 +47,7 @@ public class RandomPopulationFactory : IRandomPopulationFactory
       private readonly IReportGenerator _reportGenerator;
       private readonly IMoleculeParameterVariabilityCreator _moleculeParameterVariabilityCreator;
       private readonly IMoleculeOntogenyVariabilityUpdater _moleculeOntogenyVariabilityUpdater;
-      private readonly IDiseaseStateImplementationFactory _diseaseStateImplementationFactory;
+      private readonly IDiseaseStateImplementationRepository _diseaseStateImplementationRepository;
       private Queue<Gender> _genderQueue;
       private const int _maxIterations = 100;
 
@@ -63,7 +63,7 @@ public RandomPopulationFactory(
          IReportGenerator reportGenerator,
          IMoleculeParameterVariabilityCreator moleculeParameterVariabilityCreator,
          IMoleculeOntogenyVariabilityUpdater moleculeOntogenyVariabilityUpdater,
-         IDiseaseStateImplementationFactory diseaseStateImplementationFactory)
+         IDiseaseStateImplementationRepository diseaseStateImplementationRepository)
       {
          _objectBaseFactory = objectBaseFactory;
          _progressManager = progressManager;
@@ -76,7 +76,7 @@ public RandomPopulationFactory(
          _reportGenerator = reportGenerator;
          _moleculeParameterVariabilityCreator = moleculeParameterVariabilityCreator;
          _moleculeOntogenyVariabilityUpdater = moleculeOntogenyVariabilityUpdater;
-         _diseaseStateImplementationFactory = diseaseStateImplementationFactory;
+         _diseaseStateImplementationRepository = diseaseStateImplementationRepository;
       }
 
       public Task<RandomPopulation> CreateFor(RandomPopulationSettings populationSettings, CancellationToken cancellationToken, int? seed = null, bool addMoleculeParametersVariability = true)
@@ -90,7 +90,7 @@ public Task<RandomPopulation> CreateFor(RandomPopulationSettings populationSetti
                fllUpGenderQueueBasedOn(populationSettings);
                progressUpdater.Initialize(populationSettings.NumberOfIndividuals, PKSimConstants.UI.CreatingPopulation);
 
-               var diseaseStateImplementation = _diseaseStateImplementationFactory.CreateFor(populationSettings.BaseIndividual);
+               var diseaseStateImplementation = _diseaseStateImplementationRepository.FindFor(populationSettings.BaseIndividual);
                //the base individual is used to retrieve the default values. 
                var baseIndividual = diseaseStateImplementation.CreateBaseIndividualForPopulation(populationSettings.BaseIndividual);
 
@@ -242,7 +242,7 @@ private void perturbate(Individual currentIndividual, RandomPopulationSettings p
       {
          bool success = true;
          var originData = currentIndividual.OriginData;
-         var diseaseStateImplementation = _diseaseStateImplementationFactory.CreateFor(originData.DiseaseState);
+         var diseaseStateImplementation = _diseaseStateImplementationRepository.FindFor(originData.DiseaseState);
          uint numberOfTry = 0;
          do
          {

src/PKSim.Core/Repositories/IDiseaseStateRepository.cs

@@ -1,4 +1,6 @@
-using System.Collections.Generic;
+using System;
+using System.Collections.Generic;
+using OSPSuite.Core.Domain;
 using OSPSuite.Utility.Collections;
 using PKSim.Core.Model;
 
@@ -7,6 +9,7 @@ namespace PKSim.Core.Repositories
    public interface IDiseaseStateRepository : IStartableRepository<DiseaseState>
    {
       IReadOnlyList<DiseaseState> AllFor(SpeciesPopulation population);
+      IReadOnlyList<DiseaseState> AllForExpressionProfile(Species species, QuantityType moleculeType);
 
       DiseaseState HealthyState { get; }
    }

src/PKSim.Core/Services/CKDDiseaseStateImplementation.cs

@@ -124,11 +124,6 @@ public override (bool isValid, string error) IsValid(OriginData originData)
          return (false, PKSimConstants.Error.CKDOnlyAvailableForAdult);
       }
 
-      public override void ApplyTo(Individual individual, IndividualMolecule individualMolecule)
-      {
-         //nothing to do here
-      }
-
       protected override IReadOnlyList<IParameter> ParameterChangedByDiseaseStateAsList(Individual individual)
       {
          var (hct, gfrSpec, kidneyVolume, kidneySpecificBloodFlowRate, fatVolume, plasmaProteinScaleFactorParameter, smallIntestinalTransitTime, gastricEmptyingTime) = parametersChangedByCKDAlgorithm(individual);

src/PKSim.Core/Services/DiseaseStateImplementationFactory.cs → src/PKSim.Core/Services/DiseaseStateImplementationRepository.cs

@@ -4,22 +4,22 @@
 
 namespace PKSim.Core.Services
 {
-   public class DiseaseStateImplementationFactory : IDiseaseStateImplementationFactory
+   public class DiseaseStateImplementationRepository : IDiseaseStateImplementationRepository
    {
       private readonly IRepository<IDiseaseStateImplementation> _diseaseStateImplementations;
 
-      public DiseaseStateImplementationFactory(IRepository<IDiseaseStateImplementation> diseaseStateImplementations)
+      public DiseaseStateImplementationRepository(IRepository<IDiseaseStateImplementation> diseaseStateImplementations)
       {
          _diseaseStateImplementations = diseaseStateImplementations;
       }
 
-      public IDiseaseStateImplementation CreateFor(DiseaseState diseaseState)
+      public IDiseaseStateImplementation FindFor(DiseaseState diseaseState)
       {
          //We use all here to ensure that we get new implementations every single time
          var implementation = _diseaseStateImplementations.All().SingleOrDefault(x => x.IsSatisfiedBy(diseaseState));
          return implementation ?? new HealthyDiseaseStateImplementation();
       }
 
-      public IDiseaseStateImplementation CreateFor(Individual individual) => CreateFor(individual.OriginData.DiseaseState);
+      public IDiseaseStateImplementation FindFor(Individual individual) => FindFor(individual.OriginData.DiseaseState);
    }
 }

src/PKSim.Core/Services/ExpressionProfileUpdater.cs

@@ -65,7 +65,7 @@ public class ExpressionProfileUpdater : IExpressionProfileUpdater
       private readonly ILazyLoadTask _lazyLoadTask;
       private readonly IParameterIdUpdater _parameterIdUpdater;
       private readonly IExecutionContext _executionContext;
-      private readonly IDiseaseStateImplementationFactory _diseaseStateImplementationFactory;
+      private readonly IDiseaseStateImplementationRepository _diseaseStateImplementationRepository;
 
       public ExpressionProfileUpdater(
          IParameterSetUpdater parameterSetUpdater,
@@ -76,7 +76,7 @@ public ExpressionProfileUpdater(
          ILazyLoadTask lazyLoadTask,
          IParameterIdUpdater parameterIdUpdater,
          IExecutionContext executionContext,
-         IDiseaseStateImplementationFactory diseaseStateImplementationFactory)
+         IDiseaseStateImplementationRepository diseaseStateImplementationRepository)
       {
          _parameterSetUpdater = parameterSetUpdater;
          _containerTask = containerTask;
@@ -86,7 +86,7 @@ public ExpressionProfileUpdater(
          _lazyLoadTask = lazyLoadTask;
          _parameterIdUpdater = parameterIdUpdater;
          _executionContext = executionContext;
-         _diseaseStateImplementationFactory = diseaseStateImplementationFactory;
+         _diseaseStateImplementationRepository = diseaseStateImplementationRepository;
       }
 
       public ICommand UpdateExpressionFromQuery(ExpressionProfile expressionProfile, QueryExpressionResults queryResults)
@@ -144,16 +144,6 @@ public void SynchroniseSimulationSubjectWithExpressionProfile(ISimulationSubject
          var (sourceMolecule, sourceIndividual) = expressionProfile;
          // ExpressionProfile => SimulationSubject, we want to make sure that the parameters in simulation subject are linked to their expression profile origin parameters
          synchronizeExpressionProfiles(sourceMolecule, sourceIndividual, moleculeInIndividual, simulationSubject, updateParameterOriginId: true);
-
-         //Once the synchronization was performed, apply changes to simulation subject molecules based on disease state
-         updateMoleculeParametersForDiseaseState(simulationSubject, moleculeInIndividual);
-      }
-
-      private void updateMoleculeParametersForDiseaseState(ISimulationSubject simulationSubject, IndividualMolecule moleculeInIndividual)
-      {
-         var individual = simulationSubject.Individual;
-         var diseaseStateImplementation = _diseaseStateImplementationFactory.CreateFor(individual);
-         diseaseStateImplementation.ApplyTo(individual, moleculeInIndividual);
       }
 
       public void SynchronizeExpressionProfileWithSimulationSubject(ExpressionProfile expressionProfile, ISimulationSubject simulationSubject)