%% Profile Generator

count=0;
fflag=10;
while fflag ==10 & count < 100
    fflag=0;
    count=count+1;

    %% ini_day_dh

    if dh_i==1;
       ini_day_dh=randsample(dn_total-2,1);
    end

    if dh_i==2;
       ini_day_dh=randsample(dn_total-2,2);
    end

    if dh_i==3;
       ini_day_dh=randsample(dn_total-2,3);
    end

    %% position(s) of drug holidays

    if dh_i==1;
        position_dh_i=ini_day_dh:2+ini_day_dh;
    end

    if dh_i==2;
        position_dh_i=[ini_day_dh(1,1):2+ini_day_dh(1,1),ini_day_dh(2,1):2+ini_day_dh(2,1)];
    end

    if dh_i==3;
        position_dh_i=[ini_day_dh(1,1):2+ini_day_dh(1,1),ini_day_dh(2,1):2+ini_day_dh(2,1),ini_day_dh(3,1):2+ini_day_dh(3,1)];
    end

    %% possible positions of missed doses

    a=[1:1:150];

    if dh_i~=0;
        a=[1:1:150];
        b=setdiff(a,position_dh_i);
    end

    %% positions of missed doses

    if dh_i~=0;
        position_md_i=randsample(b,md_i);
    else
        position_md_i=randsample(a,md_i);    
    end

    %% then generating timing deviates

    if dh_i==0;
        dn_taken=dn_total-(md_i);
    end

    if dh_i==1;
        dn_taken=dn_total-(md_i)-((dh_i*3));
    end

    if dh_i==2;
        u=union(position_dh_i(1,1:3),position_dh_i(1,4:6));    
        dn_taken=dn_total-(md_i)-(length(u));
    end    

    if dh_i==3;
        u2=union(position_dh_i(1,1:3),position_dh_i(1,4:6));
        uu=union(u2,position_dh_i(1,7:9));   
        dn_taken=dn_total-(md_i)-(length(uu));   
    end
    clear diff_tm_i
    for q=1:dn_taken;
           if rand()<p;
                diff_tm_i(q) = normrnd(mu1Est,sigma1Est);
           else 
                diff_tm_i(q) = normrnd(mu2Est,sigma2Est);
           end
    end

    %% criteria to discard unacceptable profiles 

    % discard NCMD occurring at least 3 doses consecutively
    if length(strfind(diff(sort(position_md_i)),[1 1]))>0
        fflag=10;
    end 

    % when dh_1==1, discard NCMD occurring right before dh at least one point of time in the profile 
    if dh_i==1;
       position_md_i_plus_1=position_md_i+1;
       combined_1_plus=horzcat(position_md_i_plus_1,position_dh_i);
       if length(strfind(diff(sort(combined_1_plus)),[0]))>0;
           fflag=10;
       end
    end

    % when dh_1==1, discard NCMD occurring right after dh at least one point of time in the profile 
    if dh_i==1;
       position_md_i_minus_1=position_md_i-1;
       combined_1_minus=horzcat(position_md_i_minus_1,position_dh_i);
       if length(strfind(diff(sort(combined_1_minus)),[0]))>0;
           fflag=10;
       end
    end

    % when dh_1==2, discard NCMD occurring right before dh at least one point of time in the profile 
    if dh_i==2;
       position_md_i_plus_1=position_md_i+1;
       u=union(position_dh_i(1,1:3),position_dh_i(1,4:6));
       combined_2_plus=horzcat(position_md_i_plus_1,u);
       if length(strfind(diff(sort(combined_2_plus)),[0]))>0;
           fflag=10;
       end 
    end

    % when dh_1==2, discard NCMD occurring right after dh at least one point of time in the profile 
    if dh_i==2;
       position_md_i_minus_1=position_md_i-1;
       u=union(position_dh_i(1,1:3),position_dh_i(1,4:6));
       combined_2_minus=horzcat(position_md_i_minus_1,u);
       if length(strfind(diff(sort(combined_2_minus)),[0]))>0
           fflag=10;
       end
    end

    % when dh_1==3, discard NCMD occurring right before dh at least one point of time in the profile 
    if dh_i==3;
       position_md_i_plus_1=position_md_i+1;
       u2=union(position_dh_i(1,1:3),position_dh_i(1,4:6));
       uu=union(u2,position_dh_i(1,7:9));
       combined_3_plus=horzcat(position_md_i_plus_1,uu);
       if length(strfind(diff(sort(combined_3_plus)),[0]))>0
           fflag=10;
       end 
    end

    % when dh_1==3, discard NCMD occurring right after dh at least one point of time in the profile 
    if dh_i==3;
       position_md_i_minus_1=position_md_i-1;
       u2=union(position_dh_i(1,1:3),position_dh_i(1,4:6));
       uu=union(u2,position_dh_i(1,7:9));
       combined_3_minus=horzcat(position_md_i_minus_1,uu);
       if length(strfind(diff(sort(combined_3_minus)),[0]))>0
           fflag=10;
       end
    end

    %% positions of timing
    clear position_diff_tm_i
    
    if dh_i==0;
        position_diff_tm_i=setdiff(a,position_md_i);
    end
    
    if dh_i==1;
        position_diff_tm_i=setdiff(a,union(position_md_i,position_dh_i));
    end
        
    if dh_i==2;
        position_diff_tm_i=setdiff(a,union(position_md_i,position_dh_i));
    end

    if dh_i==3;
        position_diff_tm_i=setdiff(a,union(position_md_i,position_dh_i));
    end
end
%% dose time
if count > 99
    stop1
end
if fflag==10
    stop2
end

dt1=[position_diff_tm_i]*24;
    
dt2=dt1+[diff_tm_i];
dt3=dt2/24;

%% dose time
 
dosetime=[0,dt3];