Fri Dec 21 13:02:05 PST 2018
;; 1. Based on: run200
;; 2. Description: Final model, posthoc PK based on published unified model. Prityfied code
;; x1. Author: Matts
$SIZES NO=3000 LIM6=1000
$PROBLEM PN survival model With individual PK
; Implemented flip comments using PsN (e.g. sim_start and sim_end to define code to be used for VPC simulations).

;Sim_start
$INPUT MID TIME DUR RATE AMT EVID CMT DV CENS CENSD STUD ADC NDOS
NAMT_MAX PL_DOSE AV_DOSE CUMDOSE DFREQ ;18
RITUX SEXX AGE BW BHT RACE BMI BSA CTYPE ALB BUN BSLD=DROP
PDUR=DROP PCPLAT PCTAX PCVINCA PCPROT ;34
PPN DIAB ECOG1 DSBUILD=DROP PK ID ET1 ET2 ET3 ET4 ET5 ET6 ;48
$DATA nonmem_gr2_Nov13_2018.csv IGNORE=@ IGNORE(TIME.LT.0)
IGNORE(STUD.EQ.29006) IGNORE(ID.EQ.639)
; 13 patients
; Unrealistic PK

;$INPUT MID TIME DUR RATE AMT EVID CMT DV CENS CENSD STUD ADC NDOS NAMT_MAX PL_DOSE AV_DOSE CUMDOSE DFREQ

; RITUX SEXX AGE BW BHT RACE BMI BSA CTYPE ALB BUN BSLD=DROP PDUR=DROP PCPLAT PCTAX PCVINCA PCPROT

; PPN DIAB ECOG1 DSBUILD=DROP ET1 ET2 ET3 ET4 ET5 ET6 PK ID

;

; $DATA ../data/nonmem_gr2_Nov13_2018_sim.csv IGNORE=@

; IGNORE(TIME.LT.0)

; IGNORE(STUD.EQ.29006) ; 13 patients

; IGNORE(ID.EQ.639) ; Unrealistic PK

;Sim_end
$SUBROUTINE ADVAN13 TRANS1 TOL=6
$MODEL COMP=(central) COMP=(peri) COMP=(effcpt) COMP=(cumhaz)
COMP=(trcpt) COMP(AUC)
$PK
;for simulation
RTTE=0
;end for simulation

; Covariate imputations etc
ageRef = 65
albref=4.0
bunref=16
bodyWeightRef=85 ; Male

IF(SEXX.EQ.1) SEX=1 ; Male
IF(SEXX.EQ.2) THEN
SEX=0 ; Female
bodyWeightRef=68
ENDIF

BWT=BW
IF(BW.EQ.-99) BWT=bodyWeightRef

; PK parameters

THETA1=0.312;1 CL
THETA2=1.21;2 V1
THETA3= 0.957;3 V2
THETA4= -1.02;4 Q
THETA5= 1.48;5 KDES
THETA6= 1.02;6 CLT
THETA7= 0.476;7 WT to CLinf
THETA8= 0.527;8 WT to V1
THETA9= 0.484;9 WT to 2
THETA10= 0.303;10 WT to Q
THETA11= 0.149;11 SEX to V1
THETA12= 0.223;12 SEX to V
THETA13= -0.212;13 power NDOS to CL

LWT75 = LOG(BWT/75)
MUX1 = THETA1+THETA7*LWT75 +THETA13*LOG(NDOS/2.4)
MUX2 = THETA2+THETA8*LWT75+THETA11*SEX
MUX3 = THETA3+THETA9*LWT75+THETA12*SEX
MUX4 = THETA4+THETA10*LWT75
MUX5 = THETA5
MUX6 = THETA6

CLINF = EXP(MUX1+ET1)
V1 = EXP(MUX2+ET2)
V2 = EXP(MUX3+ET3)
Q = EXP(MUX4+ET4)
KDES = EXP(MUX5+ET5)
CLT = EXP(MUX6+ET6)

S1 = V1/1000

;Reparameterization
K12 = Q/V1
K21 = Q/V2

; PD parameters
LOGKTR = THETA(1)+ETA(1) ; Eta1 Fixed to zero
KTR = EXP(LOGKTR) ; first order transit rate to and from transit and effect compartment
ALPHA = EXP(THETA(2)) ; slope of drug effect
BETA = EXP(THETA(3)) ; weibul function parameter

covar = THETA(4) * (BWT - 75) + THETA(5) * PPN ; covariate effects on Hazard

$DES
; PK model
CL = CLT * EXP(-KDES * T) + CLINF
K10 = CL / V1

DADT(1) = K21 * A(2) - K12 * A(1) - K10 * A(1)
DADT(2) = -K21 * A(2) + K12 * A(1)
CPT = A(1) / S1

; PD model
DADT(5) = KTR * CPT - KTR * A(5) ; Transit compartment
DADT(3) = KTR * A(5) - KTR * A(3) ; Effect compartment
A5=A(5)
A3=A(3)

EDRUGT = ALPHA * A(3)
HAZT = 0
IF(T > 0) HAZT = BETA * (EDRUGT**BETA) * (T**(BETA - 1)) * EXP(covar); WEIBULL (not defined at time zero)
DADT(4) = HAZT ; Cumulative Hazard
DADT(6) = CPT ; Cumulative AUC
AUCT=A(6) ; AUC up to time T
CAV=AUCT/T ; Average concentration up to time T

$ERROR
CP = A(1) / S1
EDRUG = ALPHA * A(3) ; Drug effect
HAZ = 0 ; redefine Hazard in $Error. Needed to compute pdf
IF(TIME > 0) HAZ = BETA * (EDRUG**BETA) * (TIME**(BETA - 1)) * EXP(covar); WEIBULL
SURV = EXP(-A(4)) ; Survival probability
PDF=SURV*HAZ

;Estimation (defined by sim start and end)
;Sim_start
IF(DV.EQ.0) THEN
Y=SURV
CHLAST=A(4)
ELSE
CHLAST=CHLAST ; Keep nmtran happy
ENDIF

IF(DV.EQ.1) THEN
Y=PDF ;pdf
ENDIF
;Sim_end


;Simulation
IF(ICALL.EQ.4) THEN
IF (NEWIND.NE.2) CALL RANDOM (2,R) ; random uniform distribution
DV=0 ; NO EVENT OCCURS
RTTE=0 ; NO EVENT OCCURS
IF(CENS.EQ.1) RTTE=1 ; RTTE set to 1 for censoring and event rows
IF(R.GT.SURV) THEN ; Event when R > SURV
DV=1 ; DV set to 1 at time of event
RTTE=1 ; RTTE set to 1 for censoring and event rows
ENDIF
Y=DV
ENDIF


$THETA -4.53 ; 1 LOGKE0
-9.69 ; 2 LOGALPHA
-0.327 ; 3 LOGBETA
0.0145 ; 4 BWT
0.434 ; 5 PPN 1/0
$OMEGA 0 FIX
;Sim_start
;$SIGMA
;0 FIXED
$ESTIMATION MAXEVAL=9999 PRINT=1 LIKE METHOD=1 LAPLACE NUMERICAL
NOABORT SIG=3
;$SIMULATION(123456) (23000 UNIFORM) ONLYSIM ; Uncomment this for VPC generation

;Sim_end
$COVARIANCE MATRIX=S UNCONDITIONAL
$TABLE TIME ID MID EVID AV_DOSE CAV AUCT CP A5 A3 HAZ SURV
FORMAT=s1PE15.9 ONEHEADER NOPRINT FILE=HZtab202


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 97) A RANDOM QUANTITY IS RAISED TO A POWER. IF THE RESULT AFFECTS
THE VALUE OF THE OBJECTIVE FUNCTION, THE USER SHOULD ENSURE THAT THE
RANDOM QUANTITY IS NEVER 0 WHEN THE POWER 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 27) THE ABBREVIATED CODE CONTAINS A SIMULATION BLOCK BUT THERE IS
NO $SIMULATION RECORD.

License Registered to: Genentech Inc
Expiration Date: 14 DEC 2019
Current Date: 21 DEC 2018
Days until program expires : 358
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
PN survival model With individual PK
0DATA CHECKOUT RUN: NO
DATA SET LOCATED ON UNIT NO.: 2
THIS UNIT TO BE REWOUND: NO
NO. OF DATA RECS IN DATA SET: 5269
NO. OF DATA ITEMS IN DATA SET: 45
ID DATA ITEM IS DATA ITEM NO.: 38
DEP VARIABLE IS DATA ITEM NO.: 8
MDV DATA ITEM IS DATA ITEM NO.: 45
0INDICES PASSED TO SUBROUTINE PRED:
6 2 5 4 0 0 7 0 0 0 0
0LABELS FOR DATA ITEMS:
MID TIME DUR RATE AMT EVID CMT DV CENS CENSD STUD ADC NDOS NAMT_MAX PL_DOSE AV_DOSE CUMDOSE DFREQ RITUX SEXX AGE BW BHT
RACE BMI BSA CTYPE ALB BUN PCPLAT PCTAX PCVINCA PCPROT PPN DIAB ECOG1 PK ID ET1 ET2 ET3 ET4 ET5 ET6 MDV
0(NONBLANK) LABELS FOR PRED-DEFINED ITEMS:
A5 A3 AUCT CAV CP HAZ SURV
0FORMAT FOR DATA:
(11(4E19.0/)/1F2.0)

TOT. NO. OF OBS RECS: 693
TOT. NO. OF INDIVIDUALS: 693
0LENGTH OF THETA: 5
0DEFAULT THETA BOUNDARY TEST OMITTED: NO
0OMEGA HAS SIMPLE DIAGONAL FORM WITH DIMENSION: 1
0DEFAULT OMEGA BOUNDARY TEST OMITTED: NO
0INITIAL ESTIMATE OF THETA:
-0.4530E+01 -0.9690E+01 -0.3270E+00 0.1450E-01 0.4340E+00
0INITIAL ESTIMATE OF OMEGA:
0.0000E+00
0OMEGA CONSTRAINED TO BE THIS INITIAL ESTIMATE
0COVARIANCE STEP OMITTED: NO
R MATRIX SUBSTITUTED: NO
S MATRIX SUBSTITUTED: YES
EIGENVLS. PRINTED: NO
SPECIAL COMPUTATION: NO
COMPRESSED FORMAT: NO
SLOW GRADIENT METHOD USED: YES
SIGDIGITS ETAHAT (SIGLO): -1
SIGDIGITS GRADIENTS (SIGL): -1
RELATIVE TOLERANCE (TOL): -1
ABSOLUTE TOLERANCE-ADVAN 9,13 ONLY (ATOL): -1
EXCLUDE COV FOR FOCE (NOFCOV): NO
RESUME COV ANALYSIS (RESUME): NO
0TABLES STEP OMITTED: NO
NO. OF TABLES: 1
SEED NUMBER (SEED): 11456
RANMETHOD:
MC SAMPLES (ESEED): 300
WRES SQUARE ROOT TYPE: EIGENVALUE
0-- TABLE 1 --
PRINTED: NO
HEADERS: ONE
FILE TO BE FORWARDED: NO
FORMAT: s1PE15.9
LFORMAT:
RFORMAT:
0USER-CHOSEN ITEMS:
TIME ID MID EVID AV_DOSE CAV AUCT CP A5 A3 HAZ SURV
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: 11
0COMPARTMENT ATTRIBUTES
COMPT. NO. FUNCTION INITIAL ON/OFF DOSE DEFAULT DEFAULT
STATUS ALLOWED ALLOWED FOR DOSE FOR OBS.
1 CENTRAL ON YES YES YES YES
2 PERI ON YES YES NO NO
3 EFFCPT ON YES YES NO NO
4 CUMHAZ ON YES YES NO NO
5 TRCPT ON YES YES NO NO
6 AUC ON YES YES NO NO
7 OUTPUT OFF YES NO NO NO
0NRD VALUE(S) FROM SUBROUTINE TOL: 6
1
ADDITIONAL PK PARAMETERS - ASSIGNMENT OF ROWS IN GG
COMPT. NO. INDICES
SCALE BIOAVAIL. ZERO-ORDER ZERO-ORDER ABSORB
FRACTION RATE DURATION LAG
1 12 * * * *
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
0DATA ITEM INDICES USED BY PRED ARE:
EVENT ID DATA ITEM IS DATA ITEM NO.: 6
TIME DATA ITEM IS DATA ITEM NO.: 2
DOSE AMOUNT DATA ITEM IS DATA ITEM NO.: 5
DOSE RATE DATA ITEM IS DATA ITEM NO.: 4
COMPT. NO. DATA ITEM IS DATA ITEM NO.: 7

0PK SUBROUTINE CALLED WITH EVERY EVENT RECORD.
PK SUBROUTINE NOT CALLED AT NONEVENT (ADDITIONAL OR LAGGED) DOSE TIMES.
0ERROR SUBROUTINE CALLED WITH EVERY EVENT RECORD.
0ERROR SUBROUTINE INDICATES THAT DERIVATIVES OF COMPARTMENT AMOUNTS ARE USED.
0DES SUBROUTINE USES FULL STORAGE MODE.

#PARA: PARAFILE=mpilinux8.pnm, PROTOCOL=MPI, NODES= 10

1


#TBLN: 1
#METH: Laplacian Conditional Estimation

ESTIMATION STEP OMITTED: NO
ANALYSIS TYPE: POPULATION
SLOW GRADIENT METHOD USED: YES
CONDITIONAL ESTIMATES USED: YES
CENTERED ETA: NO
EPS-ETA INTERACTION: NO
LAPLACIAN OBJ. FUNC.: YES
NUMERICAL 2ND DERIVATIVES: YES
PRED F SET TO A LIKELIHOOD: YES
NO. OF FUNCT. EVALS. ALLOWED: 9999
NO. OF SIG. FIGURES REQUIRED: 3
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=NPRED
RES=NRES
WRES=NWRES
IWRS=NIWRES
IPRD=NIPRED
IRS=NIRES

MONITORING OF SEARCH:


0ITERATION NO.: 0 OBJECTIVE VALUE: 2515.12240823625 NO. OF FUNC. EVALS.: 6
CUMULATIVE NO. OF FUNC. EVALS.: 6
NPARAMETR: -4.5300E+00 -9.6900E+00 -3.2700E-01 1.4500E-02 4.3400E-01
PARAMETER: -1.0000E-01 -1.0000E-01 -1.0000E-01 1.0000E-01 1.0000E-01
GRADIENT: 1.0050E+01 3.8147E+01 2.8849E-01 -1.4232E+00 -1.1816E+00

0ITERATION NO.: 1 OBJECTIVE VALUE: 2515.12240823625 NO. OF FUNC. EVALS.: 17
CUMULATIVE NO. OF FUNC. EVALS.: 23
NPARAMETR: -4.5300E+00 -9.6900E+00 -3.2700E-01 1.4500E-02 4.3400E-01
PARAMETER: -1.0000E-01 -1.0000E-01 -1.0000E-01 1.0000E-01 1.0000E-01
GRADIENT: -2.0064E+01 -5.2477E+01 -6.3764E-02 -1.5919E+00 -1.3244E+00

0ITERATION NO.: 2 OBJECTIVE VALUE: 2515.12209453222 NO. OF FUNC. EVALS.: 17
CUMULATIVE NO. OF FUNC. EVALS.: 40 RESET HESSIAN, TYPE I
NPARAMETR: -4.5292E+00 -9.6886E+00 -3.2699E-01 1.4565E-02 4.3590E-01
PARAMETER: -9.9983E-02 -9.9986E-02 -9.9995E-02 1.0045E-01 1.0044E-01
GRADIENT: 5.2919E+01 1.1410E+02 -3.7211E-01 1.1565E+00 1.5468E+00

0ITERATION NO.: 3 OBJECTIVE VALUE: 2515.12209453222 NO. OF FUNC. EVALS.: 10
CUMULATIVE NO. OF FUNC. EVALS.: 50
NPARAMETR: -4.5292E+00 -9.6886E+00 -3.2699E-01 1.4565E-02 4.3590E-01
PARAMETER: -9.9983E-02 -9.9986E-02 -9.9995E-02 1.0045E-01 1.0044E-01
GRADIENT: 2.2775E+01 2.3209E+01 -7.2664E-01 9.8636E-01 1.4028E+00

0ITERATION NO.: 4 OBJECTIVE VALUE: 2515.12167335663 NO. OF FUNC. EVALS.: 12
CUMULATIVE NO. OF FUNC. EVALS.: 62
NPARAMETR: -4.5295E+00 -9.6882E+00 -3.2683E-01 1.4543E-02 4.3458E-01
PARAMETER: -9.9988E-02 -9.9981E-02 -9.9948E-02 1.0030E-01 1.0013E-01
GRADIENT: 1.2470E+01 7.4067E+00 -1.4422E-01 2.3810E-01 4.5344E-01

0ITERATION NO.: 5 OBJECTIVE VALUE: 2515.12154323813 NO. OF FUNC. EVALS.: 12
CUMULATIVE NO. OF FUNC. EVALS.: 74
NPARAMETR: -4.5301E+00 -9.6878E+00 -3.2680E-01 1.4543E-02 4.3392E-01
PARAMETER: -1.0000E-01 -9.9977E-02 -9.9938E-02 1.0030E-01 9.9982E-02
GRADIENT: 4.8719E+00 -4.2148E+00 2.2972E-01 2.0959E-02 -1.1415E-01

0ITERATION NO.: 6 OBJECTIVE VALUE: 2515.12154323813 NO. OF FUNC. EVALS.: 0
CUMULATIVE NO. OF FUNC. EVALS.: 74
NPARAMETR: -4.5301E+00 -9.6878E+00 -3.2680E-01 1.4543E-02 4.3392E-01
PARAMETER: -1.0000E-01 -9.9977E-02 -9.9938E-02 1.0030E-01 9.9982E-02
GRADIENT: 4.8719E+00 -4.2148E+00 2.2972E-01 2.0959E-02 -1.1415E-01

#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: 74
NO. OF SIG. DIGITS IN FINAL EST.: 3.4

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: 0.0000E+00
SE: 0.0000E+00
N: 693

P VAL.: 1.0000E+00

ETAshrink(%): 1.0000E+02
EBVshrink(%): 0.0000E+00
EPSshrink(%): 1.0000E+02

#TERE:
Elapsed estimation time in seconds: 3.72
Elapsed covariance time in seconds: 0.71
1




















************************************************************************************************************************
******************** ********************
******************** LAPLACIAN CONDITIONAL ESTIMATION ********************
#OBJT:************** MINIMUM VALUE OF OBJECTIVE FUNCTION ********************
******************** ********************
************************************************************************************************************************






#OBJV:******************************************** 2515.122 **************************************************
1
************************************************************************************************************************
******************** ********************
******************** LAPLACIAN CONDITIONAL ESTIMATION ********************
******************** FINAL PARAMETER ESTIMATE ********************
******************** ********************
************************************************************************************************************************



THETA - VECTOR OF FIXED EFFECTS PARAMETERS *********


TH 1 TH 2 TH 3 TH 4 TH 5

-4.53E+00 -9.69E+00 -3.27E-01 1.45E-02 4.34E-01



OMEGA - COV MATRIX FOR RANDOM EFFECTS - ETAS ********


ETA1

ETA1
+ 0.00E+00

1


OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS *******


ETA1

ETA1
+ 0.00E+00

1
************************************************************************************************************************
******************** ********************
******************** LAPLACIAN CONDITIONAL ESTIMATION ********************
******************** STANDARD ERROR OF ESTIMATE ********************
******************** ********************
************************************************************************************************************************



THETA - VECTOR OF FIXED EFFECTS PARAMETERS *********


TH 1 TH 2 TH 3 TH 4 TH 5

4.46E-01 5.11E-01 9.09E-02 4.20E-03 1.54E-01



OMEGA - COV MATRIX FOR RANDOM EFFECTS - ETAS ********


ETA1

ETA1
+ .........

1


OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS *******


ETA1

ETA1
+ .........

1
************************************************************************************************************************
******************** ********************
******************** LAPLACIAN CONDITIONAL ESTIMATION ********************
******************** COVARIANCE MATRIX OF ESTIMATE ********************
******************** ********************
************************************************************************************************************************


TH 1 TH 2 TH 3 TH 4 TH 5 OM11

TH 1
+ 1.99E-01

TH 2
+ -2.19E-01 2.62E-01

TH 3
+ 3.45E-02 -3.84E-02 8.26E-03

TH 4
+ -2.73E-04 1.42E-04 -3.99E-05 1.76E-05

TH 5
+ -2.53E-03 -1.24E-02 9.20E-04 2.31E-05 2.36E-02

OM11
+ ......... ......... ......... ......... ......... .........

1
************************************************************************************************************************
******************** ********************
******************** LAPLACIAN CONDITIONAL ESTIMATION ********************
******************** CORRELATION MATRIX OF ESTIMATE ********************
******************** ********************
************************************************************************************************************************


TH 1 TH 2 TH 3 TH 4 TH 5 OM11

TH 1
+ 4.46E-01

TH 2
+ -9.57E-01 5.11E-01

TH 3
+ 8.50E-01 -8.27E-01 9.09E-02

TH 4
+ -1.46E-01 6.62E-02 -1.05E-01 4.20E-03

TH 5
+ -3.69E-02 -1.57E-01 6.59E-02 3.58E-02 1.54E-01

OM11
+ ......... ......... ......... ......... ......... .........

1
************************************************************************************************************************
******************** ********************
******************** LAPLACIAN CONDITIONAL ESTIMATION ********************
******************** INVERSE COVARIANCE MATRIX OF ESTIMATE ********************
******************** ********************
************************************************************************************************************************


TH 1 TH 2 TH 3 TH 4 TH 5 OM11

TH 1
+ 1.39E+02

TH 2
+ 1.05E+02 9.20E+01

TH 3
+ -9.38E+01 -1.30E+01 4.55E+02

TH 4
+ 9.96E+02 7.79E+02 -2.73E+02 6.47E+04

TH 5
+ 7.26E+01 5.92E+01 -3.43E+01 4.62E+02 8.21E+01

OM11
+ ......... ......... ......... ......... ......... .........

#CPUT: Total CPU Time in Seconds, 39.825
Stop Time:
Fri Dec 21 13:02:24 PST 2018
