AbstractCellPopulation.cpp

/*
 
Copyright (c) 2005-2024, University of Oxford.
All rights reserved.
 
University of Oxford means the Chancellor, Masters and Scholars of the
University of Oxford, having an administrative office at Wellington
Square, Oxford OX1 2JD, UK.
 
This file is part of Chaste.
 
Redistribution and use in source and binary forms, with or without
modification, are permitted provided that the following conditions are met:
 * Redistributions of source code must retain the above copyright notice,
   this list of conditions and the following disclaimer.
 * Redistributions in binary form must reproduce the above copyright notice,
   this list of conditions and the following disclaimer in the documentation
   and/or other materials provided with the distribution.
 * Neither the name of the University of Oxford nor the names of its
   contributors may be used to endorse or promote products derived from this
   software without specific prior written permission.
 
THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS"
AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE
IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE
ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT HOLDER OR CONTRIBUTORS BE
LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR
CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE
GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION)
HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT
LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT
OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
 
*/
 
#include <boost/bind.hpp>
 
#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 "CellMutationStatesCountWriter.hpp"
#include "CellProliferativePhasesCountWriter.hpp"
#include "CellProliferativeTypesCountWriter.hpp"
#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 std::vector<boost::shared_ptr<AbstractCellProperty> >& 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[0], &mutation_counts[0], 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 std::vector<boost::shared_ptr<AbstractCellProperty> >& 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[0], &total_types_counts[0], 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[0], &phase_counts[0], 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;
    BOOST_FOREACH(boost::shared_ptr<cell_writer_t> p_cell_writer, mCellWriters)
    {
        p_cell_writer->CloseFile();
    }
 
    typedef AbstractCellPopulationWriter<ELEMENT_DIM, SPACE_DIM> pop_writer_t;
    BOOST_FOREACH(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;
    BOOST_FOREACH(boost::shared_ptr<cell_writer_t> p_cell_writer, mCellWriters)
    {
        p_cell_writer->CloseFile();
    }
 
    typedef AbstractCellPopulationWriter<ELEMENT_DIM, SPACE_DIM> pop_writer_t;
    BOOST_FOREACH(boost::shared_ptr<pop_writer_t> p_pop_writer, mCellPopulationWriters)
    {
        p_pop_writer->CloseFile();
    }
 
#ifdef CHASTE_VTK
    *mpVtkMetaFile << "    </Collection>\n";
    *mpVtkMetaFile << "</VTKFile>\n";
    mpVtkMetaFile->close();
#endif //CHASTE_VTK
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::OpenWritersFiles(OutputFileHandler& rOutputFileHandler)
{
#ifdef CHASTE_VTK
    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";
#endif //CHASTE_VTK
 
    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;
    BOOST_FOREACH(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;
    BOOST_FOREACH(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;
    BOOST_FOREACH(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;
    BOOST_FOREACH(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;
    BOOST_FOREACH(boost::shared_ptr<cell_writer_t> p_cell_writer, mCellWriters)
    {
        p_cell_writer->OpenOutputFileForAppend(rOutputFileHandler);
    }
    BOOST_FOREACH(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())
            {
                BOOST_FOREACH(boost::shared_ptr<cell_writer_t> p_cell_writer, mCellWriters)
                {
                    p_cell_writer->WriteTimeStamp();
                }
                BOOST_FOREACH(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())
            {
                BOOST_FOREACH(boost::shared_ptr<cell_writer_t> p_cell_writer, mCellWriters)
                {
                    p_cell_writer->WriteNewline();
                }
                BOOST_FOREACH(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
            BOOST_FOREACH(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
            BOOST_FOREACH(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
            BOOST_FOREACH(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
            BOOST_FOREACH(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>;