From: "Xiao, Alan" 
Subject: [NMusers] Math problem
Date:Thu, 15 May 2003 14:59:08 -0400

Hello, Dear NMusers,

Could anyone talk a bittle bit about the following message?

This message was generated when I ran a NONMEM program, which was created
from another program (running without any problem) by fixing some ETA values
as zero.  



****************************************************************************
**

 WARNINGS AND ERRORS (IF ANY) FOR PROBLEM  1

 (WARNING  2) NM-TRAN INFERS THAT THE DATA ARE POPULATION.

 (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.
        1 file(s) copied.
Starting nonmem execution ...

run-time error M6201: MATH
- asin: DOMAIN error
Image              PC        Routine            Line        Source
nonmem.exe         0049D349  Unknown               Unknown  Unknown
nonmem.exe         0049D1A7  Unknown               Unknown  Unknown
nonmem.exe         0049D301  Unknown               Unknown  Unknown
nonmem.exe         0049B8F8  Unknown               Unknown  Unknown
nonmem.exe         0049B36E  Unknown               Unknown  Unknown
nonmem.exe         004C4CAC  Unknown               Unknown  Unknown
nonmem.exe         004BDF30  Unknown               Unknown  Unknown
nonmem.exe         004BA649  Unknown               Unknown  Unknown
nonmem.exe         00471110  Unknown               Unknown  Unknown
nonmem.exe         00444CC1  Unknown               Unknown  Unknown
nonmem.exe         004214CC  Unknown               Unknown  Unknown
nonmem.exe         0041DC6B  Unknown               Unknown  Unknown
nonmem.exe         004C8D39  Unknown               Unknown  Unknown
nonmem.exe         004BA0E4  Unknown               Unknown  Unknown
KERNEL32.dll       77F1B9EA  Unknown               Unknown  Unknown
        1 file(s) copied.

***************************************************************************

Thanks,


Alan.
_______________________________________________________

From:   Leonid Gibiansky 
Subject:Re: [NMusers] Math problem
Date:Thu, 15 May 2003 15:30:33 -0400

Domain error usually means that you are trying to use function in the wrong 
domain, e.g., SQRT(-1), log(0). etc. Here the program mentioned  asin 
(arc-sine ?)  For asin, Domain Error occur in asin(x) is x is not in the 
range [-1,1]. Can it be due to rounding error around 1 or -1 ? 
Alternatively, asin can be hidden deep inside the code or in some other 
system functions. It is hard to say anything specific without looking on 
the code. As usual, try to start with new initial values.
Leonid
_______________________________________________________

From: "Serge Guzy" 
Subject:RE: [NMusers] Math problem
Date:Thu, 15 May 2003 14:17:11 -0700

You should write the following before asin(x) computation is performed

IF(X.LT.-1)THEN
X=-1
ENDIF
IF(X.GT.1)THEN
X=1
ENDIF

It is possible that rounding errors cause X to be a little bit outside the possible range
for X [-1,1].
If you do not have access to the code that computes asin, then I do not have any option
to suggest.

Serge Guzy
President POP-PHARM
_______________________________________________________

From: "Xiao, Alan" 
Subject: RE: [NMusers] Math problem
Date:Fri, 16 May 2003 08:56:54 -0400

Serge & Leonid,

Thanks for your reply. 

But, I guess what we are facing at here is related to the source code
running behind?  Or other reasons? - At least I have never used a function
of asin(x) or similar. 

I am wondering whether only I have come across this problem. It's definitely
not a big deal to influence the modeling process because I can easily go
around it with adjustments in models and/or initial guesses.  --- Just a
little curiosity on the source of this problem itself.

Another question which might be a little bit distracting - Has anyone tried
Fourier Transformation in NONMEM?

Have a nice weekend,

Alan.
_______________________________________________________

From:"Lewis B. Sheiner" 
Subject:Re: [NMusers] Math problem
Date:Fri, 16 May 2003 12:42:54 -0700

This may help: when you constrain a parameter in NONMEM to be between 
finite lower and upper bounds, I believe the program uses the arcsin 
transformation to enforce the constraint.  If this is what is happening, 
and NONMEM is somehow running into a problem applying this 
transformation (which  appears to be the case in your problem), then 
this is a NONMEM problem, not your problem, and the folks art Globomax 
should perhaps be asked to address it ...

LBS.
_______________________________________________________

From:"Xiao, Alan" 
Subject: RE: [NMusers] Math problem
Date: Sun, 18 May 2003 23:14:51 -0400


That's exactly the case - with bounds for PK parameters. 

Thanks.

Alan.
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