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What does GUTS stand for?


Originally GUTS was meant as "Grand Unified Theory for Survival" (as a tongue-in-cheek reference to the GUTs in particle physics). Later, we changed it to the more suitable "General Unified Threshold model for Survival", but kept the acronym (which is the most important thing anyway).

What is GUTS all about


Toxicokinetic-toxicodynamic modelling (see about DEBtox for explanation) for survival has been quite popular over the last two decades. Many, apparently very different, models have been developed, which has led to confusion among model developers and model users. In 2010, Roman Ashauer and Thomas Preuss organised a workshop in Eawag's facilities in Kastanienbaum, Switzerland, to discuss TKTD models, with a specific aim to address this confusion in survival models. The participants are shown in the picture, but it's up to you to find out who's who.

During the discussions (and at night, somewhere between sleeping and being awake), I realised that (almost) all published TKTD models for survival are related; they can be seen as special cases of one over-arching framework. These special cases result by setting parameters of an over-arching model (which became GUTS) to specific values. In this way, GUTS shows how these apparently very different models are related, and aids the exploration of the most useful representation of survival for particular species-chemical-data combinations.




Where is GUTS published?


A group of four people from the workshop worked out the details of GUTS and published it: the two organisers (Roman and Thomas), together with Carlo Albert and myself. GUTS was published in Environmental Science & Technology in 2011, and can be found as DOI 10.1021/es103092a. A practical worked-out example of a simple GUTS analysis on a standard data set can be found here. I collect the papers that apply hazard models (specific cases of the GUTS framework) in over here. Also, check out Roman's page on GUTS.

Latest news: Roman and myself will be working on an extensive e-book on GUTS. A first version is expected in the second half of 2017. More information.

Why don't all individuals die at the same time?


There are two very different views on this, which have been combined in GUTS. The most popular view in current-day ecotoxicology is 'individual tolerance' (IT). IT assumes that an organism dies when some dose metric (e.g., the internal concentration or body residue) exceeds a threshold. Not all organisms die at the same time because each organism has a different value for the threshold. It is often assumed that the threshold follows a log-normal distribution in the test population, which underlies the popular probit analysis.

The alternative view is 'stochastic death' (SD). SD assumes that all animals do not die at the same time because death is best viewed as a chance process. Each individual in a test container has the same probability to die, but chance decides which ones will go. This leads to a different statistical approach named survival analysis. Survival analysis is popular in many fields (e.g., insurance and engineering), but not too well known in ecotoxicology. A nice discussion on this subject was written by Newman and McCloskey (2009).




What is the relationship between GUTS and DEBtox?


GUTS and DEBtox are both TKTD approaches, and show some overlap. GUTS deals with survival only (and possibly other quantal endpoints), whereas DEBtox deals with a whole range of organism responses (not only survival, but also growth, reproduction, and in principle also respiration, body composition, product formation, etc. etc.). The survival component of DEBtox models is always some special case of GUTS; most commonly the simple hazard model with scaled internal concentrations.

It is good to realise that DEB theory includes the survival aspects of life history as well, and focusses on stochastic death (SD) as the dominant process. GUTS deals only with survival, and additionally considers individual tolerance (IT) and combinations of IT and SD. GUTS models are derived and used without reference to DEB theory (as there are no energetic aspects considered). Therefore, it is confusing to refer to GUTS models as DEB or DEBtox models, although this is done in some publications. 







Is there software for GUTS?


Yes, I provide Matlab packages for DEBtoxM and the BYOM platform (the latter being more flexible and more upt to date), and there is an R-package produced by Carlo Albert and Sören Vogel. You can also find (links to) software in R and Matlab in the software section on this website. If you have a version of the 'DEBtox for Windows', you can still use that for the DEBtox-style survival analysis (scaled toxicokinetics, constant exposure, hazard model), but the use of this software for sub-lethal effects is not recommended (I think there are some errors in the program, and it is not maintained anymore). There is currently quite some work going on with people developing GUTS implementations, and user interfaces for them, so more is about to emerge in the near future. I will try to keep track of what comes out in the miscellaneous software section.

Is there a course on DEBtox?


At this moment, there is no dedicated course on GUTS, although the summercourse DynModTox covers this topic to some extent (and there is a lot of freedom in the course). Given enough interest, we might be tempted to organise a dedicated course on GUTS.

Workshop 'Mainstreaming GUTS' 2015


In 2015, we had another GUTS workshop, 5 years after Kastanienbaum, this time at the lovely island of Mallorca. From the work done at this workshop, we have generated the following paper (Open Access):

Ashauer R, Albert C, Augustine C, Cedergreen N, Charles S, Ducrot V, Focks A, Gabsi F, Gergs A, Goussen B, Jager T, Kramer NI, Nyman AM, Poulsen V, Reichenberger S, Schäfer RB, Van den Brink PJ, Veltman K, Vogel S, Zimmer EI and Preuss TG (2016). Modelling survival: exposure pattern, species sensitivity and uncertainty. Sci Rep 6:29178 http://dx.doi.org/10.1038/srep29178






Participants in the second international GUTS workshop on Mallorca in 2015.


The DEBtox information site, www.debtox.info, since July 2011