AbstractCellPopulation.cpp

/*
 
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All rights reserved.
 
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This file is part of Chaste.
 
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 * Redistributions of source code must retain the above copyright notice,
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   software without specific prior written permission.
 
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AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE
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*/
 
#include <algorithm>
#include <functional>
 
#include "AbstractCellPopulation.hpp"
#include "AbstractPhaseBasedCellCycleModel.hpp"
#include "SmartPointers.hpp"
#include "CellAncestor.hpp"
#include "ApoptoticCellProperty.hpp"
 
// Cell writers
#include "BoundaryNodeWriter.hpp"
#include "CellProliferativeTypesWriter.hpp"
#include "LegacyCellProliferativeTypesWriter.hpp"
#include "CellRemovalLocationsWriter.hpp"
 
// Cell population writers
#include "NodeLocationWriter.hpp"
 
// These #includes are needed for SetDefaultCellMutationStateAndProliferativeTypeOrdering()
#include "WildTypeCellMutationState.hpp"
#include "ApcOneHitCellMutationState.hpp"
#include "ApcTwoHitCellMutationState.hpp"
#include "BetaCateninOneHitCellMutationState.hpp"
#include "DefaultCellProliferativeType.hpp"
#include "StemCellProliferativeType.hpp"
#include "TransitCellProliferativeType.hpp"
#include "DifferentiatedCellProliferativeType.hpp"
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::AbstractCellPopulation( AbstractMesh<ELEMENT_DIM, SPACE_DIM>& rMesh,
                                    std::vector<CellPtr>& rCells,
                                    const std::vector<unsigned> locationIndices)
    : mrMesh(rMesh),
      mCells(rCells.begin(), rCells.end()),
      mCentroid(zero_vector<double>(SPACE_DIM)),
      mpCellPropertyRegistry(CellPropertyRegistry::Instance()->TakeOwnership()),
      mOutputResultsForChasteVisualizer(true)
{
    /*
     * To avoid double-counting problems, clear the passed-in cells vector.
     * We force a reallocation of memory so that subsequent usage of the
     * vector is more likely to give an error.
     */
    std::vector<CellPtr>().swap(rCells);
 
    // There must be a one-one correspondence between cells and location indices
    if (!locationIndices.empty())
    {
        if (mCells.size() != locationIndices.size())
        {
            EXCEPTION("There is not a one-one correspondence between cells and location indices");
        }
    }
 
    // Set up the map between location indices and cells
    mLocationCellMap.clear();
    mCellLocationMap.clear();
 
    std::list<CellPtr>::iterator it = mCells.begin();
    for (unsigned i=0; it != mCells.end(); ++it, ++i)
    {
        // Give each cell a pointer to the property registry (we have taken ownership in this constructor)
        (*it)->rGetCellPropertyCollection().SetCellPropertyRegistry(mpCellPropertyRegistry.get());
    }
 
    // Clear stored divisions and removals information
    ClearDivisionsInformation();
    ClearRemovalsInformation();
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::AbstractCellPopulation(AbstractMesh<ELEMENT_DIM, SPACE_DIM>& rMesh)
    : mrMesh(rMesh)
{
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::~AbstractCellPopulation()
{
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::InitialiseCells()
{
    for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter=this->Begin();
         cell_iter!=this->End();
         ++cell_iter)
    {
        cell_iter->InitialiseCellCycleModel();
        cell_iter->InitialiseSrnModel();
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::SetDataOnAllCells(const std::string& rDataName, double dataValue)
{
    for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter=this->Begin();
         cell_iter!=this->End();
         ++cell_iter)
    {
        cell_iter->GetCellData()->SetItem(rDataName, dataValue);
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
AbstractMesh<ELEMENT_DIM, SPACE_DIM>& AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::rGetMesh()
{
    return mrMesh;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::list<CellPtr>& AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::rGetCells()
{
    return mCells;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
unsigned AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetNumRealCells()
{
    unsigned counter = 0;
    for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter=this->Begin();
         cell_iter!=this->End();
         ++cell_iter)
    {
        counter++;
    }
    return counter;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
unsigned AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetNumAllCells()
{
    return mCells.size();
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::SetCellAncestorsToLocationIndices()
{
    for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter=this->Begin(); cell_iter!=this->End(); ++cell_iter)
    {
        MAKE_PTR_ARGS(CellAncestor, p_cell_ancestor, (mCellLocationMap[(*cell_iter).get()]));
        cell_iter->SetAncestor(p_cell_ancestor);
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::set<unsigned> AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetCellAncestors()
{
    std::set<unsigned> remaining_ancestors;
    for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter=this->Begin(); cell_iter!=this->End(); ++cell_iter)
    {
        remaining_ancestors.insert(cell_iter->GetAncestor());
    }
    return remaining_ancestors;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::vector<unsigned> AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetCellMutationStateCount()
{
    std::vector<unsigned> mutation_state_count;
    const auto& r_cell_properties = mpCellPropertyRegistry->rGetAllCellProperties();
 
    // Calculate mutation states count
    for (unsigned i=0; i<r_cell_properties.size(); i++)
    {
        if (r_cell_properties[i]->IsSubType<AbstractCellMutationState>())
        {
            mutation_state_count.push_back(r_cell_properties[i]->GetCellCount());
        }
    }
 
    // Reduce results onto all processes
    if (PetscTools::IsParallel())
    {
        // Make sure the vector on each process has the same size
        unsigned local_size = mutation_state_count.size();
        unsigned global_size;
        MPI_Allreduce(&local_size, &global_size, 1, MPI_UNSIGNED, MPI_MAX, PetscTools::GetWorld());
        assert(local_size == global_size);
 
        std::vector<unsigned> mutation_counts(global_size);
        MPI_Allreduce(mutation_state_count.data(), mutation_counts.data(), mutation_counts.size(), MPI_UNSIGNED, MPI_SUM, PetscTools::GetWorld());
 
        mutation_state_count = mutation_counts;
    }
 
    return mutation_state_count;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::vector<unsigned> AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetCellProliferativeTypeCount()
{
    std::vector<unsigned> proliferative_type_count;
    const auto& r_cell_properties = mpCellPropertyRegistry->rGetAllCellProperties();
 
    // Calculate proliferative types count
    for (unsigned i=0; i<r_cell_properties.size(); i++)
    {
        if (r_cell_properties[i]->IsSubType<AbstractCellProliferativeType>())
        {
            proliferative_type_count.push_back(r_cell_properties[i]->GetCellCount());
        }
    }
 
    // Reduce results onto all processes
    if (PetscTools::IsParallel())
    {
        // Make sure the vector on each process has the same size
        unsigned local_size = proliferative_type_count.size();
        unsigned global_size;
 
        MPI_Allreduce(&local_size, &global_size, 1, MPI_UNSIGNED, MPI_MAX, PetscTools::GetWorld());
        assert(local_size == global_size);
 
        std::vector<unsigned> total_types_counts(global_size);
        MPI_Allreduce(proliferative_type_count.data(), total_types_counts.data(), total_types_counts.size(), MPI_UNSIGNED, MPI_SUM, PetscTools::GetWorld());
 
        proliferative_type_count = total_types_counts;
    }
 
    return proliferative_type_count;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::vector<unsigned> AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetCellCyclePhaseCount()
{
    std::vector<unsigned> cell_cycle_phase_count(5);
    for (unsigned i=0; i<5; i++)
    {
        cell_cycle_phase_count[i] = 0;
    }
 
    /*
     * Note that in parallel with a poor partition a process could end up with zero cells
     * in which case the calculation should be skipped since `this->Begin()` is not defined.
     */
    if (GetNumAllCells() > 0u)
    {
        if (dynamic_cast<AbstractPhaseBasedCellCycleModel*>((*(this->Begin()))->GetCellCycleModel()) == nullptr)
        {
            EXCEPTION("You are trying to record the cell cycle phase of cells with a non phase based cell cycle model.");
        }
 
        for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter = this->Begin();
             cell_iter != this->End();
             ++cell_iter)
        {
            switch (static_cast<AbstractPhaseBasedCellCycleModel*>((*cell_iter)->GetCellCycleModel())->GetCurrentCellCyclePhase())
            {
                case G_ZERO_PHASE:
                    cell_cycle_phase_count[0]++;
                    break;
                case G_ONE_PHASE:
                    cell_cycle_phase_count[1]++;
                    break;
                case S_PHASE:
                    cell_cycle_phase_count[2]++;
                    break;
                case G_TWO_PHASE:
                    cell_cycle_phase_count[3]++;
                    break;
                case M_PHASE:
                    cell_cycle_phase_count[4]++;
                    break;
                default:
                    NEVER_REACHED;
            }
        }
    }
 
    // Reduce results onto all processes
    if (PetscTools::IsParallel())
    {
        std::vector<unsigned> phase_counts(cell_cycle_phase_count.size(), 0u);
        MPI_Allreduce(cell_cycle_phase_count.data(), phase_counts.data(), phase_counts.size(), MPI_UNSIGNED, MPI_SUM, PetscTools::GetWorld());
 
        cell_cycle_phase_count = phase_counts;
    }
 
    return cell_cycle_phase_count;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
CellPtr AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetCellUsingLocationIndex(unsigned index)
{
    // Get the set of pointers to cells corresponding to this location index
    std::set<CellPtr> cells = mLocationCellMap[index];
 
    // If there is only one cell attached return the cell. Note currently only one cell per index.
    if (cells.size() == 1)
    {
        return *(cells.begin());
    }
    if (cells.empty())
    {
        EXCEPTION("Location index input argument does not correspond to a Cell");
    }
    else
    {
        EXCEPTION("Multiple cells are attached to a single location index.");
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::set<CellPtr> AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetCellsUsingLocationIndex(unsigned index)
{
    // Return the set of pointers to cells corresponding to this location index, note the set may be empty.
    return mLocationCellMap[index];
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
bool AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::IsCellAttachedToLocationIndex(unsigned index)
{
    // Get the set of pointers to cells corresponding to this location index
    std::set<CellPtr> cells = mLocationCellMap[index];
 
    // Return whether there is a cell attached to the location index
    return !(cells.empty());
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::WriteDataToVisualizerSetupFile(out_stream& pVizSetupFile)
{
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::SetCellUsingLocationIndex(unsigned index, CellPtr pCell)
{
    // Clear the maps
    mLocationCellMap[index].clear();
    mCellLocationMap.erase(pCell.get());
 
    // Replace with new cell
    mLocationCellMap[index].insert(pCell);
 
    // Do other half of the map
    mCellLocationMap[pCell.get()] = index;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::AddCellUsingLocationIndex(unsigned index, CellPtr pCell)
{
    mLocationCellMap[index].insert(pCell);
    mCellLocationMap[pCell.get()] = index;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::RemoveCellUsingLocationIndex(unsigned index, CellPtr pCell)
{
    std::set<CellPtr>::iterator cell_iter = mLocationCellMap[index].find(pCell);
 
    if (cell_iter == mLocationCellMap[index].end())
    {
        EXCEPTION("Tried to remove a cell which is not attached to the given location index");
    }
    else
    {
        mLocationCellMap[index].erase(cell_iter);
        mCellLocationMap.erase(pCell.get());
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::MoveCellInLocationMap(CellPtr pCell, unsigned old_index, unsigned new_index)
{
    // Remove the cell from its current location
    RemoveCellUsingLocationIndex(old_index, pCell);
 
    // Add it to the new location
    AddCellUsingLocationIndex(new_index, pCell);
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
unsigned AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetLocationIndexUsingCell(CellPtr pCell)
{
    // Check the cell is in the map
    assert(this->mCellLocationMap.find(pCell.get()) != this->mCellLocationMap.end());
 
    return mCellLocationMap[pCell.get()];
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
boost::shared_ptr<CellPropertyRegistry> AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetCellPropertyRegistry()
{
    return mpCellPropertyRegistry;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::SetDefaultCellMutationStateAndProliferativeTypeOrdering()
{
    boost::shared_ptr<CellPropertyRegistry> p_registry = GetCellPropertyRegistry();
    if (!p_registry->HasOrderingBeenSpecified())
    {
        std::vector<boost::shared_ptr<AbstractCellProperty> > mutations_and_proliferative_types;
        mutations_and_proliferative_types.push_back(p_registry->Get<WildTypeCellMutationState>());
        mutations_and_proliferative_types.push_back(p_registry->Get<ApcOneHitCellMutationState>());
        mutations_and_proliferative_types.push_back(p_registry->Get<ApcTwoHitCellMutationState>());
        mutations_and_proliferative_types.push_back(p_registry->Get<BetaCateninOneHitCellMutationState>());
        mutations_and_proliferative_types.push_back(p_registry->Get<StemCellProliferativeType>());
        mutations_and_proliferative_types.push_back(p_registry->Get<TransitCellProliferativeType>());
        mutations_and_proliferative_types.push_back(p_registry->Get<DifferentiatedCellProliferativeType>());
 
        // Parallel process with no cells won't have the default property, so add it in
        mutations_and_proliferative_types.push_back(p_registry->Get<DefaultCellProliferativeType>());
        p_registry->SpecifyOrdering(mutations_and_proliferative_types);
    }
}
 
/*
 * We exclude the following from coverage, as these methods are implemented elsewhere and tested accordingly
 */
// LCOV_EXCL_START
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::set<std::pair<unsigned, unsigned>> AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetNeighbouringEdgeIndices(CellPtr cell, unsigned pEdgeLocalIndex)
{
    return std::set<std::pair<unsigned, unsigned>>();
}
// LCOV_EXCL_STOP
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
c_vector<double, SPACE_DIM> AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetCentroidOfCellPopulation()
{
    mCentroid = zero_vector<double>(SPACE_DIM);
    for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter = this->Begin();
         cell_iter != this->End();
         ++cell_iter)
    {
        mCentroid += GetLocationOfCellCentre(*cell_iter);
    }
    mCentroid /= this->GetNumRealCells();
 
    return mCentroid;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::UpdateCellProcessLocation()
{
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::CloseRoundRobinWritersFiles()
{
    typedef AbstractCellWriter<ELEMENT_DIM, SPACE_DIM> cell_writer_t;
    for (boost::shared_ptr<cell_writer_t> p_cell_writer : mCellWriters)
    {
        p_cell_writer->CloseFile();
    }
 
    typedef AbstractCellPopulationWriter<ELEMENT_DIM, SPACE_DIM> pop_writer_t;
    for (boost::shared_ptr<pop_writer_t> p_pop_writer : mCellPopulationWriters)
    {
        p_pop_writer->CloseFile();
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::CloseWritersFiles()
{
    typedef AbstractCellWriter<ELEMENT_DIM, SPACE_DIM> cell_writer_t;
    for (boost::shared_ptr<cell_writer_t> p_cell_writer : mCellWriters)
    {
        p_cell_writer->CloseFile();
    }
 
    typedef AbstractCellPopulationWriter<ELEMENT_DIM, SPACE_DIM> pop_writer_t;
    for (boost::shared_ptr<pop_writer_t> p_pop_writer : mCellPopulationWriters)
    {
        p_pop_writer->CloseFile();
    }
 
    *mpVtkMetaFile << "    </Collection>\n";
    *mpVtkMetaFile << "</VTKFile>\n";
    mpVtkMetaFile->close();
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::OpenWritersFiles(OutputFileHandler& rOutputFileHandler)
{
    mpVtkMetaFile = rOutputFileHandler.OpenOutputFile("results.pvd");
    *mpVtkMetaFile << "<?xml version=\"1.0\"?>\n";
    *mpVtkMetaFile << "<VTKFile type=\"Collection\" version=\"0.1\" byte_order=\"LittleEndian\" compressor=\"vtkZLibDataCompressor\">\n";
    *mpVtkMetaFile << "    <Collection>\n";
 
    if (mOutputResultsForChasteVisualizer)
    {
        if (!HasWriter<NodeLocationWriter>())
        {
            AddPopulationWriter<NodeLocationWriter>();
        }
        if (!HasWriter<BoundaryNodeWriter>())
        {
            AddPopulationWriter<BoundaryNodeWriter>();
        }
        if (!HasWriter<CellProliferativeTypesWriter>())
        {
            AddCellWriter<CellProliferativeTypesWriter>();
        }
        if (!HasWriter<LegacyCellProliferativeTypesWriter>())
        {
            AddCellWriter<LegacyCellProliferativeTypesWriter>();
        }
    }
 
    // Open output files for any cell writers
    typedef AbstractCellWriter<ELEMENT_DIM, SPACE_DIM> cell_writer_t;
    for (boost::shared_ptr<cell_writer_t> p_cell_writer : mCellWriters)
    {
        p_cell_writer->OpenOutputFile(rOutputFileHandler);
    }
 
    // Open output files and write headers for any population writers
    typedef AbstractCellPopulationWriter<ELEMENT_DIM, SPACE_DIM> pop_writer_t;
    for (boost::shared_ptr<pop_writer_t> p_pop_writer : mCellPopulationWriters)
    {
        p_pop_writer->OpenOutputFile(rOutputFileHandler);
        p_pop_writer->WriteHeader(this);
    }
 
    // Open output files and write headers for any population count writers
    typedef AbstractCellPopulationCountWriter<ELEMENT_DIM, SPACE_DIM> count_writer_t;
    for (boost::shared_ptr<count_writer_t> p_count_writer : mCellPopulationCountWriters)
    {
        p_count_writer->OpenOutputFile(rOutputFileHandler);
        p_count_writer->WriteHeader(this);
    }
 
    // Open output files and write headers for any population event writers
    typedef AbstractCellPopulationEventWriter<ELEMENT_DIM, SPACE_DIM> event_writer_t;
    for (boost::shared_ptr<event_writer_t> p_event_writer : mCellPopulationEventWriters)
    {
        p_event_writer->OpenOutputFile(rOutputFileHandler);
        p_event_writer->WriteHeader(this);
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::OpenRoundRobinWritersFilesForAppend(OutputFileHandler& rOutputFileHandler)
{
    typedef AbstractCellWriter<ELEMENT_DIM, SPACE_DIM> cell_writer_t;
    typedef AbstractCellPopulationWriter<ELEMENT_DIM, SPACE_DIM> pop_writer_t;
    for (boost::shared_ptr<cell_writer_t> p_cell_writer : mCellWriters)
    {
        p_cell_writer->OpenOutputFileForAppend(rOutputFileHandler);
    }
    for (boost::shared_ptr<pop_writer_t> p_pop_writer : mCellPopulationWriters)
    {
        p_pop_writer->OpenOutputFileForAppend(rOutputFileHandler);
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::WriteResultsToFiles(const std::string& rDirectory)
{
    typedef AbstractCellWriter<ELEMENT_DIM, SPACE_DIM> cell_writer_t;
    typedef AbstractCellPopulationWriter<ELEMENT_DIM, SPACE_DIM> pop_writer_t;
    OutputFileHandler output_file_handler(rDirectory, false);
 
    if (!(mCellWriters.empty() && mCellPopulationWriters.empty() && mCellPopulationCountWriters.empty()))
    {
        // An ordering must be specified for cell mutation states and cell proliferative types
        SetDefaultCellMutationStateAndProliferativeTypeOrdering();
 
        PetscTools::BeginRoundRobin();
        {
            OpenRoundRobinWritersFilesForAppend(output_file_handler);
 
            // The master process writes time stamps
            if (PetscTools::AmMaster())
            {
                for (boost::shared_ptr<cell_writer_t> p_cell_writer : mCellWriters)
                {
                    p_cell_writer->WriteTimeStamp();
                }
                for (boost::shared_ptr<pop_writer_t> p_pop_writer : mCellPopulationWriters)
                {
                    p_pop_writer->WriteTimeStamp();
                }
            }
 
            for (typename std::vector<boost::shared_ptr<AbstractCellPopulationWriter<ELEMENT_DIM, SPACE_DIM> > >::iterator pop_writer_iter = mCellPopulationWriters.begin();
                 pop_writer_iter != mCellPopulationWriters.end();
                 ++pop_writer_iter)
            {
                AcceptPopulationWriter(*pop_writer_iter);
            }
 
            AcceptCellWritersAcrossPopulation();
 
            // The top-most process adds a newline
            if (PetscTools::AmTopMost())
            {
                for (boost::shared_ptr<cell_writer_t> p_cell_writer : mCellWriters)
                {
                    p_cell_writer->WriteNewline();
                }
                for (boost::shared_ptr<pop_writer_t> p_pop_writer : mCellPopulationWriters)
                {
                    p_pop_writer->WriteNewline();
                }
            }
            CloseRoundRobinWritersFiles();
        }
        PetscTools::EndRoundRobin();
 
        // Outside the round robin, deal with population count writers
        typedef AbstractCellPopulationCountWriter<ELEMENT_DIM, SPACE_DIM> count_writer_t;
 
        if (PetscTools::AmMaster())
        {
            // Open mCellPopulationCountWriters in append mode for writing, and write time stamps
            for (boost::shared_ptr<count_writer_t> p_count_writer : mCellPopulationCountWriters)
            {
                p_count_writer->OpenOutputFileForAppend(output_file_handler);
                p_count_writer->WriteTimeStamp();
            }
        }
        for (typename std::vector<boost::shared_ptr<AbstractCellPopulationCountWriter<ELEMENT_DIM, SPACE_DIM> > >::iterator count_writer_iter = mCellPopulationCountWriters.begin();
             count_writer_iter != mCellPopulationCountWriters.end();
             ++count_writer_iter)
        {
            AcceptPopulationCountWriter(*count_writer_iter);
        }
 
        if (PetscTools::AmMaster())
        {
            // Add a newline and close any output files
            for (boost::shared_ptr<count_writer_t> p_count_writer : mCellPopulationCountWriters)
            {
                p_count_writer->WriteNewline();
                p_count_writer->CloseFile();
            }
        }
 
 
        // Outside the round robin, deal with population event writers
        typedef AbstractCellPopulationEventWriter<ELEMENT_DIM, SPACE_DIM> event_writer_t;
 
        if (PetscTools::AmMaster())
        {
            // Open mCellPopulationCountWriters in append mode for writing
            for (boost::shared_ptr<event_writer_t> p_event_writer : mCellPopulationEventWriters)
            {
                p_event_writer->OpenOutputFileForAppend(output_file_handler);
            }
        }
        for (typename std::vector<boost::shared_ptr<AbstractCellPopulationEventWriter<ELEMENT_DIM, SPACE_DIM> > >::iterator event_writer_iter = mCellPopulationEventWriters.begin();
             event_writer_iter != mCellPopulationEventWriters.end();
             ++event_writer_iter)
        {
            AcceptPopulationEventWriter(*event_writer_iter);
        }
 
        if (PetscTools::AmMaster())
        {
            // Close any output files
            for (boost::shared_ptr<event_writer_t> p_event_writer : mCellPopulationEventWriters)
            {
                p_event_writer->CloseFile();
            }
        }
    }
 
    // VTK can only be written in 2 or 3 dimensions
    if (SPACE_DIM > 1)
    {
       WriteVtkResultsToFile(rDirectory);
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::AcceptCellWritersAcrossPopulation()
{
    for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter = this->Begin();
         cell_iter != this->End();
         ++cell_iter)
    {
        for (typename std::vector<boost::shared_ptr<AbstractCellWriter<ELEMENT_DIM, SPACE_DIM> > >::iterator cell_writer_iter = mCellWriters.begin();
             cell_writer_iter != mCellWriters.end();
             ++cell_writer_iter)
        {
            AcceptCellWriter(*cell_writer_iter, *cell_iter);
        }
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::OutputCellPopulationInfo(out_stream& rParamsFile)
{
    std::string cell_population_type = GetIdentifier();
 
    *rParamsFile << "\t<" << cell_population_type << ">\n";
    OutputCellPopulationParameters(rParamsFile);
    *rParamsFile << "\t</" << cell_population_type << ">\n";
    *rParamsFile << "\n";
    *rParamsFile << "\t<CellCycleModels>\n";
 
    std::set<std::string> unique_cell_cycle_models;
    std::vector<CellPtr> first_cell_with_unique_CCM;
    for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter = this->Begin();
         cell_iter != this->End();
         ++cell_iter)
    {
        std::string identifier = cell_iter->GetCellCycleModel()->GetIdentifier();
        if (unique_cell_cycle_models.count(identifier) == 0)
        {
            unique_cell_cycle_models.insert(identifier);
            first_cell_with_unique_CCM.push_back((*cell_iter));
        }
    }
 
    // Loop over unique cell-cycle models
    for (unsigned i=0; i<first_cell_with_unique_CCM.size(); i++)
    {
        // Output cell-cycle model details
        first_cell_with_unique_CCM[i]->GetCellCycleModel()->OutputCellCycleModelInfo(rParamsFile);
    }
    *rParamsFile << "\t</CellCycleModels>\n";
 
    *rParamsFile << "\n";
    *rParamsFile << "\t<SrnModels>\n";
 
    std::set<std::string> unique_srn_models;
    std::vector<CellPtr> first_cell_with_unique_SRN;
    for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter = this->Begin();
         cell_iter != this->End();
         ++cell_iter)
    {
        std::string identifier = cell_iter->GetSrnModel()->GetIdentifier();
        if (unique_srn_models.count(identifier) == 0)
        {
            unique_srn_models.insert(identifier);
            first_cell_with_unique_SRN.push_back((*cell_iter));
        }
    }
 
    // Loop over unique SRN models
    for (unsigned i=0; i<first_cell_with_unique_SRN.size(); i++)
    {
        // Output SRN model details
        first_cell_with_unique_SRN[i]->GetSrnModel()->OutputSrnModelInfo(rParamsFile);
    }
 
    *rParamsFile << "\t</SrnModels>\n";
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::OutputCellPopulationParameters(out_stream& rParamsFile)
{
    *rParamsFile << "\t\t<OutputResultsForChasteVisualizer>" << mOutputResultsForChasteVisualizer << "</OutputResultsForChasteVisualizer>\n";
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::SimulationSetupHook(AbstractCellBasedSimulation<ELEMENT_DIM, SPACE_DIM>* pSimulation)
{
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
bool AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetOutputResultsForChasteVisualizer()
{
    return mOutputResultsForChasteVisualizer;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::SetOutputResultsForChasteVisualizer(bool outputResultsForChasteVisualizer)
{
    mOutputResultsForChasteVisualizer = outputResultsForChasteVisualizer;
}
 
template <unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::vector<std::string> AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetDivisionsInformation()
{
    return mDivisionsInformation;
}
template <unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::AddDivisionInformation(std::string divisionInformation)
{
    mDivisionsInformation.push_back(divisionInformation);
}
 
template <unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::ClearDivisionsInformation()
{
    mDivisionsInformation.clear();
}
 
template <unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::vector<std::string> AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetRemovalsInformation()
{
    return mRemovalsInformation;
}
 
template <unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::AddRemovalInformation(std::string removalInformation)
{
    mRemovalsInformation.push_back(removalInformation);
}
 
template <unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::ClearRemovalsInformation()
{
    mRemovalsInformation.clear();
}
 
template <unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GenerateRemovalInformation(CellPtr pCell, std::string killerInfo)
{
    //If necessary store the information about the cell removal
    c_vector<double, SPACE_DIM> cell_location = GetLocationOfCellCentre(pCell);
    if (HasWriter<CellRemovalLocationsWriter>())
    {
        std::stringstream removal_info;
        removal_info << SimulationTime::Instance()->GetTime() << "\t";
        for (unsigned i = 0; i < SPACE_DIM; i++)
        {
            removal_info << cell_location[i] << "\t";
        }
        removal_info << "\t" << pCell->GetAge() << "\t" << pCell->GetCellId() << "\t" << killerInfo << "\t";
 
        AddRemovalInformation(removal_info.str());
    }
}
 
template <unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::KillCell(CellPtr pCell, std::string killerInfo)
{
    //If necessary store the information about the cell removal
    GenerateRemovalInformation(pCell, killerInfo);
 
    //Mark cell as dead
    pCell->Kill();
}
 
template <unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::StartApoptosisOnCell(CellPtr pCell, std::string killerInfo)
{
    //If necessary store the information about the cell removal
    GenerateRemovalInformation(pCell, killerInfo);
 
    //Mark cell as Apoptotic
    pCell->StartApoptosis();
}
 
template <unsigned ELEMENT_DIM, unsigned SPACE_DIM>
bool AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::IsRoomToDivide(CellPtr pCell)
{
    return true;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
c_vector<double,SPACE_DIM> AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::GetSizeOfCellPopulation()
{
    // Compute the centre of mass of the cell population
    c_vector<double,SPACE_DIM> centre = GetCentroidOfCellPopulation();
 
    // Loop over cells and find the maximum distance from the centre of mass in each dimension
    c_vector<double,SPACE_DIM> max_distance_from_centre = zero_vector<double>(SPACE_DIM);
    for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter = this->Begin();
         cell_iter != this->End();
         ++cell_iter)
    {
        c_vector<double,SPACE_DIM> cell_location = GetLocationOfCellCentre(*cell_iter);
 
        // Note that we define this vector before setting it as otherwise the profiling build will break (see #2367)
        c_vector<double,SPACE_DIM> displacement;
        displacement = centre - cell_location;
 
        for (unsigned i=0; i<SPACE_DIM; i++)
        {
            if (displacement[i] > max_distance_from_centre[i])
            {
                max_distance_from_centre[i] = displacement[i];
            }
        }
    }
 
    return max_distance_from_centre;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::pair<unsigned,unsigned> AbstractCellPopulation<ELEMENT_DIM,SPACE_DIM>::CreateOrderedPair(unsigned index1, unsigned index2)
{
    assert(index1 != index2);
 
    std::pair<unsigned, unsigned> ordered_pair;
    if (index1 < index2)
    {
        ordered_pair.first = index1;
        ordered_pair.second = index2;
    }
    else
    {
        ordered_pair.first = index2;
        ordered_pair.second = index1;
    }
    return ordered_pair;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
bool AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::IsPdeNodeAssociatedWithNonApoptoticCell(unsigned pdeNodeIndex)
{
    bool non_apoptotic_cell_present = false;
 
    if (IsCellAttachedToLocationIndex(pdeNodeIndex))
    {
        non_apoptotic_cell_present = !(GetCellUsingLocationIndex(pdeNodeIndex)->template HasCellProperty<ApoptoticCellProperty>());
    }
 
    return non_apoptotic_cell_present;
}
 
 
// Explicit instantiation
template class AbstractCellPopulation<1,1>;
template class AbstractCellPopulation<1,2>;
template class AbstractCellPopulation<2,2>;
template class AbstractCellPopulation<1,3>;
template class AbstractCellPopulation<2,3>;
template class AbstractCellPopulation<3,3>;