AbstractCellBasedSimulation.cpp

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*/
 
#include <cmath>
#include <iostream>
#include <fstream>
#include <set>
#include "AbstractCellBasedSimulation.hpp"
#include "CellBasedEventHandler.hpp"
#include "LogFile.hpp"
#include "ExecutableSupport.hpp"
#include "AbstractPdeModifier.hpp"
#include "CellDivisionLocationsWriter.hpp"
#include "CellRemovalLocationsWriter.hpp"
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::AbstractCellBasedSimulation(AbstractCellPopulation<ELEMENT_DIM,SPACE_DIM>& rCellPopulation,
                                              bool deleteCellPopulationInDestructor,
                                              bool initialiseCells)
    : mDt(DOUBLE_UNSET),
      mEndTime(DOUBLE_UNSET),  // hours - this is set later on
      mrCellPopulation(rCellPopulation),
      mDeleteCellPopulationInDestructor(deleteCellPopulationInDestructor),
      mInitialiseCells(initialiseCells),
      mNoBirth(false),
      mUpdateCellPopulation(true),
      mOutputDirectory(""),
      mSimulationOutputDirectory(mOutputDirectory),
      mNumBirths(0),
      mNumDeaths(0),
      mOutputDivisionLocations(false),
      mOutputCellVelocities(false),
      mSamplingTimestepMultiple(1),
      mUpdatingTimestepMultiple(1)
{
    // Set a random seed of 0 if it wasn't specified earlier
    RandomNumberGenerator::Instance();
 
    if (mInitialiseCells)
    {
        mrCellPopulation.InitialiseCells();
    }
 
    /*
     * Specify a default time step to use, which may depend on the cell population type.
     * Note that the time step may be reset using SetDt().
     */
    mDt = rCellPopulation.GetDefaultTimeStep();
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::~AbstractCellBasedSimulation()
{
    if (mDeleteCellPopulationInDestructor)
    {
        delete &mrCellPopulation;
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
unsigned AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::DoCellBirth()
{
    if (mNoBirth)
    {
        return 0;
    }
 
    unsigned num_births_this_step = 0;
 
    // Iterate over all cells, seeing if each one can be divided
    for (typename AbstractCellPopulation<ELEMENT_DIM,SPACE_DIM>::Iterator cell_iter = mrCellPopulation.Begin();
         cell_iter != mrCellPopulation.End();
         ++cell_iter)
    {
        // Check if this cell is ready to divide
        double cell_age = cell_iter->GetAge();
        if (cell_age > 0.0)
        {
            if (cell_iter->ReadyToDivide())
            {
                // Check if there is room into which the cell may divide
                if (mrCellPopulation.IsRoomToDivide(*cell_iter))
                {
                    // Store parent ID for output if required
                    unsigned parent_cell_id = cell_iter->GetCellId();
 
                    // Create a new cell
                    CellPtr p_new_cell = cell_iter->Divide();
 
                    if (mrCellPopulation.template HasWriter<CellDivisionLocationsWriter>())
                    {
                        c_vector<double, SPACE_DIM> cell_location = mrCellPopulation.GetLocationOfCellCentre(*cell_iter);
 
                        std::stringstream division_info;
                        division_info << SimulationTime::Instance()->GetTime() << "\t";
                        for (unsigned i = 0; i < SPACE_DIM; i++)
                        {
                            division_info << cell_location[i] << "\t";
                        }
                        division_info << "\t" << cell_age << "\t" << parent_cell_id << "\t" << cell_iter->GetCellId() << "\t" << p_new_cell->GetCellId() << "\t";
 
                        mrCellPopulation.AddDivisionInformation(division_info.str());
                    }
 
                    // Add the new cell to the cell population
                    mrCellPopulation.AddCell(p_new_cell, *cell_iter);
 
                    // Update counter
                    num_births_this_step++;
                }
            }
        }
    }
    return num_births_this_step;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
unsigned AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::DoCellRemoval()
{
    unsigned num_deaths_this_step = 0;
 
    /*
     * This labels cells as dead or apoptosing. It does not actually remove the cells,
     * mrCellPopulation.RemoveDeadCells() needs to be called for this.
     */
    for (typename std::vector<boost::shared_ptr<AbstractCellKiller<SPACE_DIM> > >::iterator killer_iter = mCellKillers.begin();
         killer_iter != mCellKillers.end();
         ++killer_iter)
    {
        (*killer_iter)->CheckAndLabelCellsForApoptosisOrDeath();
    }
 
    num_deaths_this_step += mrCellPopulation.RemoveDeadCells();
 
    return num_deaths_this_step;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::SetDt(double dt)
{
    assert(dt > 0);
    mDt = dt;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
double AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::GetDt()
{
    return mDt;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
unsigned AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::GetNumBirths()
{
    return mNumBirths;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
unsigned AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::GetNumDeaths()
{
    return mNumDeaths;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::SetEndTime(double endTime)
{
    assert(endTime > 0);
    mEndTime = endTime;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::SetOutputDirectory(std::string outputDirectory)
{
    mOutputDirectory = outputDirectory;
    mSimulationOutputDirectory = mOutputDirectory;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::string AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::GetOutputDirectory()
{
    return mOutputDirectory;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::SetSamplingTimestepMultiple(unsigned samplingTimestepMultiple)
{
    assert(samplingTimestepMultiple > 0);
    mSamplingTimestepMultiple = samplingTimestepMultiple;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::SetUpdatingTimestepMultiple(unsigned updatingTimestepMultiple)
{
    assert(updatingTimestepMultiple > 0);
    mUpdatingTimestepMultiple = updatingTimestepMultiple;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
AbstractCellPopulation<ELEMENT_DIM,SPACE_DIM>& AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::rGetCellPopulation()
{
    return mrCellPopulation;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
const AbstractCellPopulation<ELEMENT_DIM,SPACE_DIM>& AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::rGetCellPopulation() const
{
    return mrCellPopulation;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::SetUpdateCellPopulationRule(bool updateCellPopulation)
{
    mUpdateCellPopulation = updateCellPopulation;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
bool AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::GetUpdateCellPopulationRule()
{
    return mUpdateCellPopulation;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::SetNoBirth(bool noBirth)
{
    mNoBirth = noBirth;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::AddCellKiller(boost::shared_ptr<AbstractCellKiller<SPACE_DIM> > pCellKiller)
{
    mCellKillers.push_back(pCellKiller);
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::RemoveAllCellKillers()
{
    mCellKillers.clear();
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::AddSimulationModifier(boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM,SPACE_DIM> > pSimulationModifier)
{
    mSimulationModifiers.push_back(pSimulationModifier);
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::vector<boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM, SPACE_DIM> > >* AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::GetSimulationModifiers()
{
    return &mSimulationModifiers;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::AddTopologyUpdateSimulationModifier(boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM,SPACE_DIM> > pSimulationModifier)
{
    mTopologyUpdateSimulationModifiers.push_back(pSimulationModifier);
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::vector<boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM, SPACE_DIM> > >* AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::GetTopologyUpdateSimulationModifiers()
{
    return &mTopologyUpdateSimulationModifiers;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
std::vector<double> AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::GetNodeLocation(const unsigned& rNodeIndex)
{
    std::vector<double> location;
    for (unsigned i=0; i<SPACE_DIM; i++)
    {
        location.push_back(mrCellPopulation.GetNode(rNodeIndex)->rGetLocation()[i]);
    }
    return location;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::Solve()
{
    CellBasedEventHandler::BeginEvent(CellBasedEventHandler::EVERYTHING);
    CellBasedEventHandler::BeginEvent(CellBasedEventHandler::SETUP);
 
    // Set up the simulation time
    SimulationTime* p_simulation_time = SimulationTime::Instance();
    double current_time = p_simulation_time->GetTime();
 
    assert(mDt != DOUBLE_UNSET);  //Subclass constructors take care of this
 
    if (mEndTime == DOUBLE_UNSET)
    {
        EXCEPTION("SetEndTime has not yet been called.");
    }
 
    /*
     * Note that mDt is used here for "ideal time step". If this step doesn't divide the time remaining
     * then a *different* time step will be taken by the time-stepper. The real time-step (used in the
     * SimulationTime singleton) is currently not available to this class.
     *
     * \todo Should we over-write the value of mDt, or change this behaviour? (see #2159)
     */
    unsigned num_time_steps = (unsigned) ((mEndTime-current_time)/mDt+0.5);
    if (current_time > 0) // use the reset function if necessary
    {
        p_simulation_time->ResetEndTimeAndNumberOfTimeSteps(mEndTime, num_time_steps);
    }
    else
    {
        if (p_simulation_time->IsEndTimeAndNumberOfTimeStepsSetUp())
        {
            EXCEPTION("End time and number of timesteps already setup. You should not use SimulationTime::SetEndTimeAndNumberOfTimeSteps in cell-based tests.");
        }
        else
        {
            p_simulation_time->SetEndTimeAndNumberOfTimeSteps(mEndTime, num_time_steps);
        }
    }
 
    if (mOutputDirectory == "")
    {
        EXCEPTION("OutputDirectory not set");
    }
 
    double time_now = p_simulation_time->GetTime();
    std::ostringstream time_string;
    time_string << time_now;
 
    std::string results_directory = mOutputDirectory +"/results_from_time_" + time_string.str();
    mSimulationOutputDirectory = results_directory;
 
    // Set up simulation
 
    // Create output files for the visualizer
    OutputFileHandler output_file_handler(results_directory + "/", true);
 
    if (mOutputDivisionLocations)
    {
        mrCellPopulation.template AddCellPopulationEventWriter<CellDivisionLocationsWriter>();
        mrCellPopulation.template AddCellPopulationEventWriter<CellRemovalLocationsWriter>();
    }
    if (mOutputCellVelocities)
    {
        OutputFileHandler output_file_handler2(this->mSimulationOutputDirectory + "/", false);
        mpCellVelocitiesFile = output_file_handler2.OpenOutputFile("cellvelocities.dat");
    }
 
    mrCellPopulation.OpenWritersFiles(output_file_handler);
 
    if (PetscTools::AmMaster())
    {
        mpVizSetupFile = output_file_handler.OpenOutputFile("results.vizsetup");
 
        for (typename std::vector<boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM, SPACE_DIM> > >::iterator iter = mSimulationModifiers.begin();
             iter != mSimulationModifiers.end();
             ++iter)
        {
            if (boost::dynamic_pointer_cast<AbstractPdeModifier<SPACE_DIM> >(*iter))
            {
                *this->mpVizSetupFile << "PDE \n";
            }
        }
    }
 
    this->mrCellPopulation.SimulationSetupHook(this);
 
    SetupSolve();
 
    // Call SetupSolve() on each modifier
    for (typename std::vector<boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM, SPACE_DIM> > >::iterator iter = mSimulationModifiers.begin();
         iter != mSimulationModifiers.end();
         ++iter)
    {
        (*iter)->SetupSolve(this->mrCellPopulation,this->mSimulationOutputDirectory);
    }
 
    // Call SetupSolve() on each topology update modifier
    for (typename std::vector<boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM, SPACE_DIM> > >::iterator iter = mTopologyUpdateSimulationModifiers.begin();
            iter != mTopologyUpdateSimulationModifiers.end();
            ++iter)
    {
        (*iter)->SetupSolve(this->mrCellPopulation,this->mSimulationOutputDirectory);
    }
 
    /*
     * Age the cells to the correct time. Note that cells are created with
     * negative birth times so that some are initially almost ready to divide.
     */
    LOG(1, "Setting up cells...");
    for (typename AbstractCellPopulation<ELEMENT_DIM,SPACE_DIM>::Iterator cell_iter = mrCellPopulation.Begin();
         cell_iter != mrCellPopulation.End();
         ++cell_iter)
    {
        /*
         * We don't use the result; this call is just to force the cells to age
         * to the current time running their cell-cycle models to get there.
         */
        cell_iter->ReadyToDivide();
    }
    LOG(1, "\tdone\n");
 
    // Write initial conditions to file for the visualizer
    WriteVisualizerSetupFile();
 
    if (PetscTools::AmMaster())
    {
        *mpVizSetupFile << std::flush;
    }
 
    mrCellPopulation.WriteResultsToFiles(results_directory+"/");
 
    OutputSimulationSetup();
    CellBasedEventHandler::EndEvent(CellBasedEventHandler::SETUP);
 
    // Enter main time loop
    while (!( p_simulation_time->IsFinished() || StoppingEventHasOccurred() ) )
    {
        LOG(1, "--TIME = " << p_simulation_time->GetTime() << "\n");
 
 
        if (p_simulation_time->GetTimeStepsElapsed()%mUpdatingTimestepMultiple == 0)
        {
            // This function calls DoCellRemoval(), DoCellBirth() and CellPopulation::Update()
            UpdateCellPopulation();
        }
 
        // Store whether we are sampling results at the current timestep
        SimulationTime* p_time = SimulationTime::Instance();
        bool at_sampling_timestep = (p_time->GetTimeStepsElapsed()%this->mSamplingTimestepMultiple == 0);
 
        /*
         * If required, store the current locations of cell centres. Note that we need to
         * use a std::map between cells and locations, rather than (say) a std::vector with
         * location indices corresponding to cells, since once we call UpdateCellLocations()
         * the location index of each cell may change. This is especially true in the case
         * of a CaBasedCellPopulation.
         */
        std::map<CellPtr, c_vector<double, SPACE_DIM> > old_cell_locations;
        if (mOutputCellVelocities && at_sampling_timestep)
        {
            for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter = mrCellPopulation.Begin();
                 cell_iter != mrCellPopulation.End();
                 ++cell_iter)
            {
                old_cell_locations[*cell_iter] = mrCellPopulation.GetLocationOfCellCentre(*cell_iter);
            }
        }
 
        /* Call UpdateAtEndOfTimeStep() on each topology update modifier */
        CellBasedEventHandler::BeginEvent(CellBasedEventHandler::UPDATESIMULATION);
        for (typename std::vector<boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM, SPACE_DIM> > >::iterator iter = mTopologyUpdateSimulationModifiers.begin();
                iter != mTopologyUpdateSimulationModifiers.end();
                ++iter)
        {
            (*iter)->UpdateAtEndOfTimeStep(this->mrCellPopulation);
        }
        CellBasedEventHandler::EndEvent(CellBasedEventHandler::UPDATESIMULATION);
 
        // Update cell locations and topology
        UpdateCellLocationsAndTopology();
 
        // Now write cell velocities to file if required
        if (mOutputCellVelocities && at_sampling_timestep)
        {
            // Offset as doing this before we increase time by mDt
            *mpCellVelocitiesFile << p_time->GetTime() + mDt<< "\t";
 
            for (typename AbstractCellPopulation<ELEMENT_DIM, SPACE_DIM>::Iterator cell_iter = mrCellPopulation.Begin();
                 cell_iter != mrCellPopulation.End();
                 ++cell_iter)
            {
                unsigned index = mrCellPopulation.GetLocationIndexUsingCell(*cell_iter);
                const c_vector<double,SPACE_DIM>& position = mrCellPopulation.GetLocationOfCellCentre(*cell_iter);
 
                c_vector<double, SPACE_DIM> velocity; // Two lines for profile build
                velocity = (position - old_cell_locations[*cell_iter])/mDt;
 
                *mpCellVelocitiesFile << index  << " ";
                for (unsigned i=0; i<SPACE_DIM; i++)
                {
                    *mpCellVelocitiesFile << position[i] << " ";
                }
 
                for (unsigned i=0; i<SPACE_DIM; i++)
                {
                    *mpCellVelocitiesFile << velocity[i] << " ";
                }
            }
            *mpCellVelocitiesFile << "\n";
        }
 
        // Update the assignment of cells to processes.
        mrCellPopulation.UpdateCellProcessLocation();
 
        // Increment simulation time here, so results files look sensible
        p_simulation_time->IncrementTimeOneStep();
 
        /* Call UpdateAtEndOfTimeStep() on each modifier */
        CellBasedEventHandler::BeginEvent(CellBasedEventHandler::UPDATESIMULATION);
        for (typename std::vector<boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM, SPACE_DIM> > >::iterator iter = mSimulationModifiers.begin();
                iter != mSimulationModifiers.end();
                ++iter)
        {
            (*iter)->UpdateAtEndOfTimeStep(this->mrCellPopulation);
        }
        CellBasedEventHandler::EndEvent(CellBasedEventHandler::UPDATESIMULATION);
 
        // Output current results to file
        CellBasedEventHandler::BeginEvent(CellBasedEventHandler::OUTPUT);
        if (p_simulation_time->GetTimeStepsElapsed()%mSamplingTimestepMultiple == 0)// should be at_sampling_timestep !
        {
            mrCellPopulation.WriteResultsToFiles(results_directory+"/");
 
            // Call UpdateAtEndOfOutputTimeStep() on each modifier
            for (typename std::vector<boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM, SPACE_DIM> > >::iterator iter = mSimulationModifiers.begin();
                 iter != mSimulationModifiers.end();
                 ++iter)
            {
                (*iter)->UpdateAtEndOfOutputTimeStep(this->mrCellPopulation);
            }
        }
        CellBasedEventHandler::EndEvent(CellBasedEventHandler::OUTPUT);
    }
 
    LOG(1, "--END TIME = " << p_simulation_time->GetTime() << "\n");
 
    /*
     * Carry out a final update so that cell population is coherent with new cell positions.
     * Note that cell birth and death still need to be checked because they may be spatially
     * dependent.
     */
    UpdateCellPopulation();
 
    CellBasedEventHandler::BeginEvent(CellBasedEventHandler::UPDATESIMULATION);
    // Call UpdateAtEndOfSolve(), on each modifier
    for (typename std::vector<boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM, SPACE_DIM> > >::iterator iter = mSimulationModifiers.begin();
         iter != mSimulationModifiers.end();
         ++iter)
    {
        (*iter)->UpdateAtEndOfSolve(this->mrCellPopulation);
    }
    CellBasedEventHandler::EndEvent(CellBasedEventHandler::UPDATESIMULATION);
 
    CellBasedEventHandler::BeginEvent(CellBasedEventHandler::OUTPUT);
 
    mrCellPopulation.CloseWritersFiles();
 
    if (mOutputCellVelocities)
    {
        mpCellVelocitiesFile->close();
    }
 
    if (PetscTools::AmMaster())
    {
        *mpVizSetupFile << "Complete\n";
        mpVizSetupFile->close();
    }
 
    CellBasedEventHandler::EndEvent(CellBasedEventHandler::OUTPUT);
    CellBasedEventHandler::EndEvent(CellBasedEventHandler::EVERYTHING);
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
bool AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::StoppingEventHasOccurred()
{
    return false;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::UpdateCellPopulation()
{
    // Remove dead cells
    CellBasedEventHandler::BeginEvent(CellBasedEventHandler::DEATH);
    unsigned deaths_this_step = DoCellRemoval();
    mNumDeaths += deaths_this_step;
    LOG(1, "\tNum deaths = " << mNumDeaths << "\n");
    CellBasedEventHandler::EndEvent(CellBasedEventHandler::DEATH);
 
    // Divide cells
    CellBasedEventHandler::BeginEvent(CellBasedEventHandler::BIRTH);
    unsigned births_this_step = DoCellBirth();
    mNumBirths += births_this_step;
    LOG(1, "\tNum births = " << mNumBirths << "\n");
    CellBasedEventHandler::EndEvent(CellBasedEventHandler::BIRTH);
 
    // This allows NodeBasedCellPopulation::Update() to do the minimum amount of work
    bool births_or_death_occurred = ((births_this_step>0) || (deaths_this_step>0));
 
    // Update topology of cell population
    CellBasedEventHandler::BeginEvent(CellBasedEventHandler::UPDATECELLPOPULATION);
    SimulationTime* p_time = SimulationTime::Instance();
    if (mUpdateCellPopulation && (p_time->GetTimeStepsElapsed() % mUpdatingTimestepMultiple == 0) )
    {
        LOG(1, "\tUpdating cell population...");
        mrCellPopulation.Update(births_or_death_occurred);
        LOG(1, "\tdone.\n");
    }
    else if (births_or_death_occurred)
    {
        if (!mUpdateCellPopulation)
        {
            EXCEPTION("CellPopulation has had births or deaths but mUpdateCellPopulation is set to false, please set it to true.");
        }
        else if ((p_time->GetTimeStepsElapsed() % mUpdatingTimestepMultiple != 0))
        {
            EXCEPTION("CellPopulation has had births or deaths but you were on a non update step, make sure your cell cycle model and killer only operate on update steps.");
        }
        else
        {
            NEVER_REACHED;
        }
    }
    CellBasedEventHandler::EndEvent(CellBasedEventHandler::UPDATECELLPOPULATION);
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
bool AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::GetOutputDivisionLocations()
{
    return mOutputDivisionLocations;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::SetOutputDivisionLocations(bool outputDivisionLocations)
{
    mOutputDivisionLocations = outputDivisionLocations;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
bool AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::GetOutputCellVelocities()
{
    return mOutputCellVelocities;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::SetOutputCellVelocities(bool outputCellVelocities)
{
    mOutputCellVelocities = outputCellVelocities;
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::OutputSimulationSetup()
{
    OutputFileHandler output_file_handler(this->mSimulationOutputDirectory + "/", false);
 
    // Output machine information
    ExecutableSupport::SetOutputDirectory(output_file_handler.GetOutputDirectoryFullPath());
    ExecutableSupport::WriteMachineInfoFile("system_info");
 
    if (PetscTools::AmMaster())
    {
        // Output Chaste provenance information
        out_stream build_info_file = output_file_handler.OpenOutputFile("build.info");
        std::string build_info;
        ExecutableSupport::GetBuildInfo(build_info);
        *build_info_file << build_info;
        build_info_file->close();
 
        // Output simulation parameter and setup details
        out_stream parameter_file = output_file_handler.OpenOutputFile("results.parameters");
 
        // Output simulation details
        std::string simulation_type = GetIdentifier();
 
        *parameter_file << "<Chaste>\n";
        *parameter_file << "\n\t<" << simulation_type << ">\n";
        OutputSimulationParameters(parameter_file);
        *parameter_file << "\t</" << simulation_type << ">\n";
        *parameter_file << "\n";
 
        // Output cell population details (includes cell-cycle model details)
        mrCellPopulation.OutputCellPopulationInfo(parameter_file);
 
        // Loop over cell killers
        *parameter_file << "\n\t<CellKillers>\n";
        for (typename std::vector<boost::shared_ptr<AbstractCellKiller<SPACE_DIM> > >::iterator iter = mCellKillers.begin();
             iter != mCellKillers.end();
             ++iter)
        {
            // Output cell killer details
            (*iter)->OutputCellKillerInfo(parameter_file);
        }
        *parameter_file << "\t</CellKillers>\n";
 
        // Iterate over simulationmodifiers
        *parameter_file << "\n\t<SimulationModifiers>\n";
        for (typename std::vector<boost::shared_ptr<AbstractCellBasedSimulationModifier<ELEMENT_DIM, SPACE_DIM> > >::iterator iter = mSimulationModifiers.begin();
             iter != mSimulationModifiers.end();
             ++iter)
        {
            // Output simulation modifier details
            (*iter)->OutputSimulationModifierInfo(parameter_file);
        }
        *parameter_file << "\t</SimulationModifiers>\n";
 
        // This is used to output information about subclasses
        OutputAdditionalSimulationSetup(parameter_file);
 
        *parameter_file << "\n</Chaste>\n";
        parameter_file->close();
    }
}
 
template<unsigned ELEMENT_DIM, unsigned SPACE_DIM>
void AbstractCellBasedSimulation<ELEMENT_DIM,SPACE_DIM>::OutputSimulationParameters(out_stream& rParamsFile)
{
    *rParamsFile << "\t\t<Dt>" << mDt << "</Dt>\n";
    *rParamsFile << "\t\t<EndTime>" << mEndTime << "</EndTime>\n";
    *rParamsFile << "\t\t<UpdateCellPopulation>" << mUpdateCellPopulation << "</UpdateCellPopulation>\n";
    *rParamsFile << "\t\t<SamplingTimestepMultiple>" << mSamplingTimestepMultiple << "</SamplingTimestepMultiple>\n";
    *rParamsFile << "\t\t<UpdatingTimestepMultiple>" << mUpdatingTimestepMultiple << "</UpdatingTimestepMultiple>\n";
    *rParamsFile << "\t\t<OutputDivisionLocations>" << mOutputDivisionLocations << "</OutputDivisionLocations>\n";
    *rParamsFile << "\t\t<OutputCellVelocities>" << mOutputCellVelocities << "</OutputCellVelocities>\n";
}
 
// Explicit instantiation
template class AbstractCellBasedSimulation<1,1>;
template class AbstractCellBasedSimulation<1,2>;
template class AbstractCellBasedSimulation<2,2>;
template class AbstractCellBasedSimulation<1,3>;
template class AbstractCellBasedSimulation<2,3>;
template class AbstractCellBasedSimulation<3,3>;