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output_simulated.lst
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Sun Oct 4 22:23:52 CEST 2015
$PROBLEM Khan et al,JAC 2015
$INPUT STR ID MIC xMIC CAB TIME TUBE CMT EVID DV AMT FLG2 FLG1
BASE L2 BOBS
$DATA ciprotest.csv IGNORE=@ IGNORE=(BOBS.EQ.1)
;BOBS=baseline observaions. Here dropped,using B2 for baseline.
$SUBROUTINE ADVAN13 TOL5
$MODEL NCOMP=6 COMPARTMENT=(S) ;Compartment S1
COMPARTMENT=(R) ;Compartment R1
COMPARTMENT=(SPE) ;Compartment S2
COMPARTMENT=(NP) ;Compartment NC1
COMPARTMENT=(RPE) ;Compartment R2
COMPARTMENT=(NPPE) ;Compartment NC2
$PK
"FIRST
" COMMON /PRCOMG/ IDUM1,IDUM2,IMAX,IDUM4,IDUM5
" INTEGER IDUM1,IDUM2,IMAX,IDUM4,IDUM5
" IMAX=10000000
;;-- growth rate
KGS = THETA(1)
;;-- death rate
KK = 0.179
;;-- drug EMAX
EMAX = THETA(2)
;;-- drug EC50
IF(STR.EQ.347) EC50 = THETA(3)
IF(STR.EQ.202) EC50 = THETA(4)
IF(STR.EQ.378) EC50 = THETA(5)
IF(STR.EQ.534) EC50 = THETA(6)
IF(STR.EQ.625) EC50 = THETA(7)
IF(STR.EQ.693) EC50 = THETA(8)
IF(STR.EQ.707) EC50 = THETA(9)
;;-- hill factor drug effect
GAM = THETA(10)
;; -- proportionality constant
PC = THETA(11)*0.0000001 ; proportionality constant
;; -- baseline, B2 method
SBASE=EXP(BASE)*EXP(ETA(1)*(SIGMA(1)**0.5))
;;--growth rate 2
KGS2= THETA(12)
;;-- drug EC502
EC502= THETA(13)
;;--pre-existing resistant at start
MUT= THETA(14)
;;--compartment initialization
A_0(1)= SBASE*(1-MUT*0.000001)
A_0(2)= 0
A_0(3)= MUT*0.000001*SBASE
A_0(4)= 0
A_0(5)= 0
A_0(6)= 0
;;-- k non-colony forming compartements
KSNC1 = THETA(15) * (CAB/EC50)**THETA(17)/((CAB/EC50)**THETA(17)+THETA(18)**THETA(17))
KSNC2 = THETA(15) * (CAB/EC502)**THETA(17)/((CAB/EC502)**THETA(17)+THETA(18)**THETA(17))
KNCS1 = THETA(16)* EC50/(CAB+0.0000000001) ; avoids division by 0
KNCS2 = THETA(16)* EC502/(CAB+0.0000000001)
;;-- MTIME - shuts off KNC1
MTIME(1) = 0
MTIME(2) = MTIME(1)+THETA(19)
$DES
;;-- see MTIME
FLAG=MPAST(1)-MPAST(2)
;;-- Conversion rate between active/resting cell dependent on cell number
SR=PC*(A(1)+A(2)+A(3)+A(4)+A(5)+A(6))
SR2=SR
RS=0
RS2=0
;EMAX equation for drug effect
DRUGS=0
DRUGS2=0
IF(CAB.GT.0.00000000001)THEN
DRUGS = EMAX*(CAB)**GAM/(EC50**GAM+(CAB)**GAM)
DRUGS2 = EMAX*(CAB)**GAM/(EC502**GAM+(CAB)**GAM)
ENDIF
;;-- Dif.eq.
DADT(1)= KGS*(A(1))-(KK+DRUGS)*(A(1)) - SR*(A(1)) + RS*(A(2)) +KNCS1*A(4) -KSNC1*A(1)*FLAG ; S
DADT(2)=-KK*(A(2)) + SR*(A(1)) - RS*(A(2)) ; R
DADT(3)= KGS2*(A(3))-(KK+DRUGS2)*(A(3)) - SR2*(A(3)) + RS2*(A(5))+KNCS2*A(6) -KSNC2*A(3)*FLAG ; S2
DADT(4)= KSNC1*A(1)*FLAG - KNCS1*A(4)-(KK+DRUGS)*(A(4)) ; NC1
DADT(5)=-KK*(A(5)) + SR2*(A(3)) ; R2
DADT(6)= KSNC2*A(3)*FLAG - KNCS2*A(6)-(KK+DRUGS2)*(A(6)) ; NC2
$ERROR
SIG=SQRT(SIGMA(1)+SIGMA(2))
LLOQ=LOG(10) ;LOQ=10 (LOG=LN in NONMEM)
A1=A(1)
A2=A(2)
A3=A(3)
A4=A(4)
A5=A(5)
A6=A(6)
ATOT=A1+A2+A3+A5 ;NC not counted
DEL=0
IPRED=LOG(ATOT+1E-8)
DUM = (LLOQ-IPRED)/SIG
DUM2= PHI(DUM)
IRES = DV-IPRED
W=SQRT(SIGMA(1)+SIGMA(2))
IWRES = IRES/W
SAM1=0
SAM2=0
SAM3=0
SAM4=0
IF(FLG2.EQ.1) SAM1=1
IF(FLG2.EQ.2) SAM2=1
IF(FLG2.EQ.3) SAM3=1
IF(FLG2.EQ.4) SAM4=1
IF(FLG1.EQ.0) THEN ;DV>LOQ
F_FLAG=0
Y=IPRED+EPS(1)+SAM1*EPS(2)+SAM2*EPS(3)+SAM3*EPS(4)+SAM4*EPS(5)
ENDIF
IF(FLG1.EQ.1) THEN ;DV<LOQ
F_FLAG=1
Y=DUM2
ENDIF
$THETA (1,1.70) ; 1. kgrowth1
$THETA (0,5.24) ; 2. EMAX
$THETA (0,0.037) FIX ; 3. Ec50 347
$THETA (0,0.057) ; 4. Ec50 202 only LM202 provided in ciprotest.csv dataset '
$THETA (0,0.65) FIX ; 5. Ec50 378
$THETA (0,0.30) FIX ; 6. Ec50 534
$THETA (0,1.0) FIX ; 7. Ec50 625
$THETA (0,31) FIX ; 8. Ec50 693
$THETA (0,92) FIX ; 9. Ec50 707
$THETA (0.5,1.98) ; 10. GAM
$THETA (0,0.0186) ; 11. PC
$THETA (0.18,0.344) ; 12. kgrowth2
$THETA (0,1.25) ; 13. EC502
$THETA (0,0.81) ; 14. start conc pre-existing resistant
$THETA (0,5.83) ; 15. kSNc,max
$THETA (0,0.17) ; 16. sfNcS
$THETA (0,20) FIX ; 17. Hill factor Nc
$THETA (0,0.24) ; 18. tr50
$THETA (2,5.3158) ; 19. MTIME
$OMEGA 1 FIX ; B2 method OMEGA 1 FIX
$SIGMA 2.41597
$SIGMA BLOCK(1)
0.128122
$SIGMA BLOCK(1) SAME
$SIGMA BLOCK(1) SAME
$SIGMA BLOCK(1) SAME
$ESTIMATION METHOD=1 LAPLACIAN NUMERICAL NSIG=5 MAXEVAL=9999 POSTHOC
PRINT=1 NOABORT INTERACTION
;$COVARIANCE UNCONDITIONAL
$TABLE ID TIME CAB IPRED IWRES PRED NOPRINT ONEHEADER FILE=sdtab1
$TABLE SBASE DV BASE DRUGS ATOT A1 A2 A3 A4 CAB ID TIME KGS SR RS
KK EMAX KGS2 EC502 PRED GAM FLAG IPRED STR DRUGS2 NOPRINT
ONEHEADER FILE=patab1
NM-TRAN MESSAGES
WARNINGS AND ERRORS (IF ANY) FOR PROBLEM 1
(WARNING 2) NM-TRAN INFERS THAT THE DATA ARE POPULATION.
(WARNING 3) THERE MAY BE AN ERROR IN THE ABBREVIATED CODE. THE FOLLOWING
ONE OR MORE RANDOM VARIABLES ARE DEFINED WITH "IF" STATEMENTS THAT DO NOT
PROVIDE DEFINITIONS FOR BOTH THE "THEN" AND "ELSE" CASES. IF ALL
CONDITIONS FAIL, THE VALUES OF THESE VARIABLES WILL BE ZERO.
Y
(WARNING 90) WITH "NUMERICAL", "SLOW" IS ALSO REQUIRED ON $ESTIM RECORD.
NM-TRAN HAS SUPPLIED THIS OPTION.
(WARNING 80) $PK SETS MTIME BUT NOT MTDIFF. WHEN AN ELEMENT OF MTIME IS
RESET, THEN $PK SHOULD ALSO SET MTDIFF=1.
(WARNING 113) VERBATIM CODE CONTAINS "COMMON". IF THIS IS NOT A
USER-DEFINED COMMON, IT SHOULD BE REPLACED BY THE APPROPRIATE MODULE.
(DATA WARNING 5) RECORD 128, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 130, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 132, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 134, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 136, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 142, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 144, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 146, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 148, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 150, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 152, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 157, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 159, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 161, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 163, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 165, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 169, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 171, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 173, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1
(DATA WARNING 5) RECORD 175, DATA ITEM 10, CONTENTS: 0.693
THE DV DATA ITEM IS POSITIVE, BUT THE MDV DATA ITEM IS 1*
(WARNING 48) DES-DEFINED ITEMS ARE COMPUTED ONLY WHEN EVENT TIME
INCREASES. E.G., DISPLAYED VALUES ASSOCIATED WITH THE FIRST EVENT RECORD
OF AN INDIVIDUAL RECORD ARE COMPUTED WITH (THE LAST ADVANCE TO) AN EVENT
TIME OF THE PRIOR INDIVIDUAL RECORD.
(WARNING 79) SIGMA IS USED ON THE RIGHT. WITH A SUBSEQUENT RUN, IF AN
INITIAL ESTIMATE OF A DIAGONAL BLOCK OF SIGMA IS TO BE COMPUTED BY
NONMEM, THAT BLOCK WILL BE SET TO AN IDENTITY MATRIX DURING THAT
COMPUTATION. THIS COULD LEAD TO AN ARITHMETIC EXCEPTION.*
* THE MAXIMUM NUMBER OF WARNINGS OF ONE OR MORE TYPES WAS REACHED.
IT IS POSSIBLE THAT SOME WARNING MESSAGES WERE SUPPRESSED.
License Registered to: Uppsala University
Expiration Date: 14 MAR 2016
Current Date: 4 OCT 2015
Days until program expires : 165
1NONLINEAR MIXED EFFECTS MODEL PROGRAM (NONMEM) VERSION 7.3.0
ORIGINALLY DEVELOPED BY STUART BEAL, LEWIS SHEINER, AND ALISON BOECKMANN
CURRENT DEVELOPERS ARE ROBERT BAUER, ICON DEVELOPMENT SOLUTIONS,
AND ALISON BOECKMANN. IMPLEMENTATION, EFFICIENCY, AND STANDARDIZATION
PERFORMED BY NOUS INFOSYSTEMS.
PROBLEM NO.: 1
Khan et al,JAC 2015
0DATA CHECKOUT RUN: NO
DATA SET LOCATED ON UNIT NO.: 2
THIS UNIT TO BE REWOUND: NO
NO. OF DATA RECS IN DATA SET: 179
NO. OF DATA ITEMS IN DATA SET: 17
ID DATA ITEM IS DATA ITEM NO.: 2
L2 DATA ITEM IS DATA ITEM NO.: 15
DEP VARIABLE IS DATA ITEM NO.: 10
MDV DATA ITEM IS DATA ITEM NO.: 17
0INDICES PASSED TO SUBROUTINE PRED:
9 6 11 0 0 0 8 0 0 0 0
0LABELS FOR DATA ITEMS:
STR ID MIC xMIC CAB TIME TUBE CMT EVID DV AMT FLG2 FLG1 BASE L2 BOBS MDV
0(NONBLANK) LABELS FOR PRED-DEFINED ITEMS:
KGS KK EMAX GAM SBASE KGS2 EC502 FLAG SR RS DRUGS DRUGS2 A1 A2 A3 A4 ATOT IPRED IWRES
0FORMAT FOR DATA:
(E4.0,2E6.0,2E7.0,E3.0,3E2.0,E12.0,3E2.0,E5.0,2E2.0,1F2.0)
TOT. NO. OF OBS RECS: 148
TOT. NO. OF INDIVIDUALS: 9
0LENGTH OF THETA: 19
0DEFAULT THETA BOUNDARY TEST OMITTED: NO
0OMEGA HAS SIMPLE DIAGONAL FORM WITH DIMENSION: 1
0DEFAULT OMEGA BOUNDARY TEST OMITTED: NO
0SIGMA HAS BLOCK FORM:
1
0 2
0 0 2
0 0 0 2
0 0 0 0 2
0DEFAULT SIGMA BOUNDARY TEST OMITTED: NO
0INITIAL ESTIMATE OF THETA:
LOWER BOUND INITIAL EST UPPER BOUND
0.1000E+01 0.1700E+01 0.1000E+07
0.0000E+00 0.5240E+01 0.1000E+07
0.3700E-01 0.3700E-01 0.3700E-01
0.0000E+00 0.5700E-01 0.1000E+07
0.6500E+00 0.6500E+00 0.6500E+00
0.3000E+00 0.3000E+00 0.3000E+00
0.1000E+01 0.1000E+01 0.1000E+01
0.3100E+02 0.3100E+02 0.3100E+02
0.9200E+02 0.9200E+02 0.9200E+02
0.5000E+00 0.1980E+01 0.1000E+07
0.0000E+00 0.1860E-01 0.1000E+07
0.1800E+00 0.3440E+00 0.1000E+07
0.0000E+00 0.1250E+01 0.1000E+07
0.0000E+00 0.8100E+00 0.1000E+07
0.0000E+00 0.5830E+01 0.1000E+07
0.0000E+00 0.1700E+00 0.1000E+07
0.2000E+02 0.2000E+02 0.2000E+02
0.0000E+00 0.2400E+00 0.1000E+07
0.2000E+01 0.5316E+01 0.1000E+07
0INITIAL ESTIMATE OF OMEGA:
0.1000E+01
0OMEGA CONSTRAINED TO BE THIS INITIAL ESTIMATE
0INITIAL ESTIMATE OF SIGMA:
BLOCK SET NO. BLOCK FIXED
1 NO
0.2416E+01
2 NO
0.1281E+00
0TABLES STEP OMITTED: NO
NO. OF TABLES: 2
SEED NUMBER (SEED): 11456
RANMETHOD:
MC SAMPLES (ESEED): 300
WRES SQUARE ROOT TYPE: EIGENVALUE
0-- TABLE 1 --
PRINTED: NO
HEADER: YES
FILE TO BE FORWARDED: NO
FORMAT: S1PE11.4
LFORMAT:
RFORMAT:
0USER-CHOSEN ITEMS:
ID TIME CAB IPRED IWRES
0-- TABLE 2 --
PRINTED: NO
HEADER: YES
FILE TO BE FORWARDED: NO
FORMAT: S1PE11.4
LFORMAT:
RFORMAT:
0USER-CHOSEN ITEMS:
SBASE DV BASE DRUGS ATOT A1 A2 A3 A4 CAB ID TIME KGS SR RS KK EMAX KGS2 EC502 GAM FLAG IPRED STR DRUGS2
0WARNING: THE NUMBER OF PARAMETERS TO BE ESTIMATED
EXCEEDS THE NUMBER OF INDIVIDUALS WITH DATA.
1DOUBLE PRECISION PREDPP VERSION 7.3.0
GENERAL NONLINEAR KINETICS MODEL USING LSODA (ADVAN13)
0MODEL SUBROUTINE USER-SUPPLIED - ID NO. 9999
0MAXIMUM NO. OF BASIC PK PARAMETERS: 12
0COMPARTMENT ATTRIBUTES
COMPT. NO. FUNCTION INITIAL ON/OFF DOSE DEFAULT DEFAULT
STATUS ALLOWED ALLOWED FOR DOSE FOR OBS.
1 S ON YES YES YES YES
2 R ON YES YES NO NO
3 SPE ON YES YES NO NO
4 NP ON YES YES NO NO
5 RPE ON YES YES NO NO
6 NPPE ON YES YES NO NO
7 OUTPUT OFF YES NO NO NO
0NRD VALUE(S) FROM SUBROUTINE TOL: 5
1
ADDITIONAL PK PARAMETERS - ASSIGNMENT OF ROWS IN GG
COMPT. NO. INDICES
SCALE BIOAVAIL. ZERO-ORDER ZERO-ORDER ABSORB
FRACTION RATE DURATION LAG
1 * * * * *
2 * * * * *
3 * * * * *
4 * * * * *
5 * * * * *
6 * * * * *
7 * - - - -
- PARAMETER IS NOT ALLOWED FOR THIS MODEL
* PARAMETER IS NOT SUPPLIED BY PK SUBROUTINE;
WILL DEFAULT TO ONE IF APPLICABLE
0FIRST MODEL TIME PARAMETER ASSIGNED TO ROW NO.: 13
LAST MODEL TIME PARAMETER ASSIGNED TO ROW NO.: 14
0DATA ITEM INDICES USED BY PRED ARE:
EVENT ID DATA ITEM IS DATA ITEM NO.: 9
TIME DATA ITEM IS DATA ITEM NO.: 6
DOSE AMOUNT DATA ITEM IS DATA ITEM NO.: 11
COMPT. NO. DATA ITEM IS DATA ITEM NO.: 8
0PK SUBROUTINE CALLED WITH EVERY EVENT RECORD.
PK SUBROUTINE CALLED AT NONEVENT (ADDITIONAL AND LAGGED) DOSE TIMES AND AT MODEL TIMES.
0PK SUBROUTINE INDICATES THAT COMPARTMENT AMOUNTS ARE INITIALIZED.
0ERROR SUBROUTINE CALLED WITH EVERY EVENT RECORD.
0ERROR SUBROUTINE INDICATES THAT DERIVATIVES OF COMPARTMENT AMOUNTS ARE USED.
0DES SUBROUTINE USES FULL STORAGE MODE.
1
#TBLN: 1
#METH: Laplacian Conditional Estimation with Interaction
ESTIMATION STEP OMITTED: NO
ANALYSIS TYPE: POPULATION
SLOW GRADIENT METHOD USED: YES
CONDITIONAL ESTIMATES USED: YES
CENTERED ETA: NO
EPS-ETA INTERACTION: YES
LAPLACIAN OBJ. FUNC.: YES
NUMERICAL 2ND DERIVATIVES: YES
NO. OF FUNCT. EVALS. ALLOWED: 9999
NO. OF SIG. FIGURES REQUIRED: 5
INTERMEDIATE PRINTOUT: YES
ESTIMATE OUTPUT TO MSF: NO
ABORT WITH PRED EXIT CODE 1: NO
IND. OBJ. FUNC. VALUES SORTED: NO
NUMERICAL DERIVATIVE
FILE REQUEST (NUMDER): NONE
MAP (ETAHAT) ESTIMATION METHOD (OPTMAP): 0
ETA HESSIAN EVALUATION METHOD (ETADER): 0
INITIAL ETA FOR MAP ESTIMATION (MCETA): 0
SIGDIGITS FOR MAP ESTIMATION (SIGLO): 100
GRADIENT SIGDIGITS OF
FIXED EFFECTS PARAMETERS (SIGL): 100
EXCLUDE TITLE (NOTITLE): NO
EXCLUDE COLUMN LABELS (NOLABEL): NO
NOPRIOR SETTING (NOPRIOR): OFF
NOCOV SETTING (NOCOV): OFF
DERCONT SETTING (DERCONT): OFF
ABSOLUTE TOLERANCE-ADVAN 9,13 ONLY(ATOL):-100
FINAL ETA RE-EVALUATION (FNLETA): ON
EXCLUDE NON-INFLUENTIAL (NON-INFL.) ETAS
IN SHRINKAGE (ETASTYPE): NO
NON-INFL. ETA CORRECTION (NONINFETA): OFF
FORMAT FOR ADDITIONAL FILES (FORMAT): S1PE12.5
PARAMETER ORDER FOR OUTPUTS (ORDER): TSOL
ADDITIONAL CONVERGENCE TEST (CTYPE=4)?: NO
EM OR BAYESIAN METHOD USED: NONE
THE FOLLOWING LABELS ARE EQUIVALENT
PRED=PREDI
RES=RESI
WRES=WRESI
IWRS=IWRESI
IPRD=IPREDI
IRS=IRESI
MONITORING OF SEARCH:
0ITERATION NO.: 0 OBJECTIVE VALUE: -6.05724949031061 NO. OF FUNC. EVALS.: 15
CUMULATIVE NO. OF FUNC. EVALS.: 15
NPARAMETR: 1.7000E+00 5.2400E+00 5.7000E-02 1.9800E+00 1.8600E-02 3.4400E-01 1.2500E+00 8.1000E-01 5.8300E+00 1.7000E-01
2.4000E-01 5.3158E+00 2.4160E+00 1.2812E-01
PARAMETER: 1.0000E-01 1.0000E-01 1.0000E-01 1.0000E-01 1.0000E-01 1.0000E-01 1.0000E-01 1.0000E-01 1.0000E-01 1.0000E-01
1.0000E-01 1.0000E-01 1.0000E-01 1.0000E-01
GRADIENT: -4.5992E+05 -1.9941E+05 9.0522E+05 -3.3679E+05 -5.7549E+05 -2.7597E+05 -2.6644E+03 8.1928E+05 -6.3295E+05 -2.5961E+05
-2.1377E+05 -2.0816E+05 4.3590E+06 -2.0682E+05
0ITERATION NO.: 1 OBJECTIVE VALUE: -7.44505016538882 NO. OF FUNC. EVALS.: 16
CUMULATIVE NO. OF FUNC. EVALS.: 31
NPARAMETR: 1.7112E+00 5.2761E+00 5.5252E-02 1.9973E+00 1.8972E-02 3.4556E-01 1.2501E+00 7.8748E-01 5.9584E+00 1.7153E-01
2.4177E-01 5.3396E+00 1.7898E+00 1.2996E-01
PARAMETER: 1.1583E-01 1.0686E-01 6.8850E-02 1.1159E-01 1.1980E-01 1.0950E-01 1.0009E-01 7.1807E-02 1.2178E-01 1.0893E-01
1.0736E-01 1.0716E-01 -5.0000E-02 1.0712E-01
GRADIENT: -2.5760E+04 -3.5404E+05 2.7636E+04 9.7604E+04 -3.9997E+04 1.9226E+03 1.2852E+06 3.7795E+05 6.5259E+04 -1.0994E+05
-7.6293E+04 1.3615E+06 1.2665E+05 -1.2580E+05
0ITERATION NO.: 2 OBJECTIVE VALUE: -7.79163789506517 NO. OF FUNC. EVALS.: 18
CUMULATIVE NO. OF FUNC. EVALS.: 49
NPARAMETR: 1.7115E+00 5.3122E+00 5.5222E-02 1.9944E+00 1.8987E-02 3.4556E-01 1.2195E+00 7.8177E-01 5.9509E+00 1.7189E-01
2.4213E-01 5.2532E+00 1.7811E+00 1.3059E-01
PARAMETER: 1.1632E-01 1.1368E-01 6.8318E-02 1.0971E-01 1.2057E-01 1.0946E-01 7.5334E-02 6.4527E-02 1.2052E-01 1.1105E-01
1.0883E-01 8.0935E-02 -5.2440E-02 1.0954E-01
GRADIENT: 1.6169E+05 1.5550E+05 3.1578E+06 9.6866E+05 1.8640E+05 2.4594E+05 3.2832E+06 3.5164E+06 3.1486E+05 2.3732E+05
7.0810E+06 2.0845E+05 5.0706E+05 1.7878E+05
0ITERATION NO.: 3 OBJECTIVE VALUE: -8.50805456479894 NO. OF FUNC. EVALS.: 19
CUMULATIVE NO. OF FUNC. EVALS.: 68
NPARAMETR: 1.7115E+00 5.3117E+00 5.5122E-02 1.9936E+00 1.8985E-02 3.4554E-01 1.2172E+00 7.8019E-01 5.9498E+00 1.7187E-01
2.4114E-01 5.2528E+00 1.7800E+00 1.3056E-01
PARAMETER: 1.1623E-01 1.1359E-01 6.6498E-02 1.0915E-01 1.2047E-01 1.0932E-01 7.3442E-02 6.2500E-02 1.2034E-01 1.1091E-01
1.0474E-01 8.0815E-02 -5.2732E-02 1.0944E-01
GRADIENT: 2.8358E+06 1.3901E+06 1.0342E+06 8.8748E+05 7.9494E+05 8.3539E+05 3.2589E+06 9.6230E+05 8.6031E+05 7.4384E+05
9.3845E+05 -7.3448E+05 1.8875E+06 1.0314E+06
0ITERATION NO.: 4 OBJECTIVE VALUE: -8.50805456479894 NO. OF FUNC. EVALS.: 42
CUMULATIVE NO. OF FUNC. EVALS.: 110
NPARAMETR: 1.7115E+00 5.3117E+00 5.5122E-02 1.9936E+00 1.8985E-02 3.4554E-01 1.2172E+00 7.8019E-01 5.9498E+00 1.7187E-01
2.4114E-01 5.2528E+00 1.7800E+00 1.3056E-01
PARAMETER: 1.1623E-01 1.1359E-01 6.6498E-02 1.0915E-01 1.2047E-01 1.0932E-01 7.3442E-02 6.2500E-02 1.2034E-01 1.1091E-01
1.0474E-01 8.0815E-02 -5.2732E-02 1.0944E-01
GRADIENT: 1.0262E+06 2.2580E+05 -1.3722E+05 -4.3910E+05 -2.9002E+04 -1.5616E+05 1.0028E+06 2.9351E+05 -1.0820E+06 -4.4304E+05
1.1568E+05 -8.8595E+05 4.5818E+05 4.6234E+04
0ITERATION NO.: 5 OBJECTIVE VALUE: -10.5813616661132 NO. OF FUNC. EVALS.: 35
CUMULATIVE NO. OF FUNC. EVALS.: 145
NPARAMETR: 1.7110E+00 5.3111E+00 5.5124E-02 1.9941E+00 1.8985E-02 3.4556E-01 1.2164E+00 7.7998E-01 5.9543E+00 1.7192E-01
2.4108E-01 5.2547E+00 1.7791E+00 1.3056E-01
PARAMETER: 1.1560E-01 1.1347E-01 6.6535E-02 1.0945E-01 1.2050E-01 1.0944E-01 7.2753E-02 6.2230E-02 1.2110E-01 1.1123E-01
1.0450E-01 8.1397E-02 -5.3009E-02 1.0943E-01
GRADIENT: -9.4161E+01 -3.6037E+05 -2.2235E+05 -5.3961E+05 -1.1595E+04 3.3460E+05 1.9101E+05 -1.5781E+06 4.5628E+04 -7.3700E+04
-2.5481E+05 5.1607E+04 -3.3205E+04 1.9548E+05
0ITERATION NO.: 6 OBJECTIVE VALUE: -10.5813616661132 NO. OF FUNC. EVALS.: 14
CUMULATIVE NO. OF FUNC. EVALS.: 159
NPARAMETR: 1.7110E+00 5.3111E+00 5.5124E-02 1.9941E+00 1.8985E-02 3.4556E-01 1.2164E+00 7.7998E-01 5.9543E+00 1.7192E-01
2.4108E-01 5.2547E+00 1.7791E+00 1.3056E-01
PARAMETER: 1.1560E-01 1.1347E-01 6.6535E-02 1.0945E-01 1.2050E-01 1.0944E-01 7.2753E-02 6.2230E-02 1.2110E-01 1.1123E-01
1.0450E-01 8.1397E-02 -5.3009E-02 1.0943E-01
GRADIENT: -9.4161E+01 -3.6037E+05 -2.2235E+05 -5.3961E+05 -1.1595E+04 3.3460E+05 1.9101E+05 -8.0816E+05 4.5628E+04 -7.3700E+04
-2.5481E+05 5.1607E+04 -3.3205E+04 1.9548E+05
#TERM:
0MINIMIZATION SUCCESSFUL
HOWEVER, PROBLEMS OCCURRED WITH THE MINIMIZATION.
REGARD THE RESULTS OF THE ESTIMATION STEP CAREFULLY, AND ACCEPT THEM ONLY
AFTER CHECKING THAT THE COVARIANCE STEP PRODUCES REASONABLE OUTPUT.
NO. OF FUNCTION EVALUATIONS USED: 159
NO. OF SIG. DIGITS IN FINAL EST.: 5.2
ETABAR IS THE ARITHMETIC MEAN OF THE ETA-ESTIMATES,
AND THE P-VALUE IS GIVEN FOR THE NULL HYPOTHESIS THAT THE TRUE MEAN IS 0.
ETABAR: -3.9653E-01
SE: 2.0569E-01
N: 9
P VAL.: 5.3875E-02
ETAshrink(%): 3.4551E+01
EBVshrink(%): 6.5249E+01
EPSshrink(%): 2.2751E+01 2.2751E+01 2.2751E+01 2.3888E+01 8.4531E+00
#TERE:
Elapsed estimation time in seconds: 32.41
1
************************************************************************************************************************
******************** ********************
******************** LAPLACIAN CONDITIONAL ESTIMATION WITH INTERACTION ********************
#OBJT:************** MINIMUM VALUE OF OBJECTIVE FUNCTION ********************
******************** ********************
************************************************************************************************************************
#OBJV:******************************************** -10.581 **************************************************
1
************************************************************************************************************************
******************** ********************
******************** LAPLACIAN CONDITIONAL ESTIMATION WITH INTERACTION ********************
******************** FINAL PARAMETER ESTIMATE ********************
******************** ********************
************************************************************************************************************************
THETA - VECTOR OF FIXED EFFECTS PARAMETERS *********
TH 1 TH 2 TH 3 TH 4 TH 5 TH 6 TH 7 TH 8 TH 9 TH10 TH11 TH12
TH13 TH14 TH15 TH16 TH17 TH18 TH19
1.71E+00 5.31E+00 3.70E-02 5.51E-02 6.50E-01 3.00E-01 1.00E+00 3.10E+01 9.20E+01 1.99E+00 1.90E-02 3.46E-01
1.22E+00 7.80E-01 5.95E+00 1.72E-01 2.00E+01 2.41E-01 5.25E+00
OMEGA - COV MATRIX FOR RANDOM EFFECTS - ETAS ********
ETA1
ETA1
+ 1.00E+00
SIGMA - COV MATRIX FOR RANDOM EFFECTS - EPSILONS ****
EPS1 EPS2 EPS3 EPS4 EPS5
EPS1
+ 1.78E+00
EPS2
+ 0.00E+00 1.31E-01
EPS3
+ 0.00E+00 0.00E+00 1.31E-01
EPS4
+ 0.00E+00 0.00E+00 0.00E+00 1.31E-01
EPS5
+ 0.00E+00 0.00E+00 0.00E+00 0.00E+00 1.31E-01
1
OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS *******
ETA1
ETA1
+ 1.00E+00
SIGMA - CORR MATRIX FOR RANDOM EFFECTS - EPSILONS ***
EPS1 EPS2 EPS3 EPS4 EPS5
EPS1
+ 1.33E+00
EPS2
+ 0.00E+00 3.61E-01
EPS3
+ 0.00E+00 0.00E+00 3.61E-01
EPS4
+ 0.00E+00 0.00E+00 0.00E+00 3.61E-01
EPS5
+ 0.00E+00 0.00E+00 0.00E+00 0.00E+00 3.61E-01
#CPUT: Total CPU Time in Seconds, 32.683
Stop Time:
Sun Oct 4 22:24:27 CEST 2015