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All individuals are NOT created equal

All individuals are NOT created equal. TexPoint fonts used in EMF. Read the TexPoint manual before you delete this box.: A A A A A A. The homogeneous cohort. … is a myth. mean of responses  response of average individual. How can we solve this?. Experimental

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All individuals are NOT created equal

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  1. All individuals are NOT created equal TexPoint fonts used in EMF. Read the TexPoint manual before you delete this box.: AAAAAA

  2. The homogeneous cohort

  3. … is a myth mean of responses  response of average individual

  4. How can we solve this? Experimental • Follow individuals over time … Modelling • Each individual with its own set of parameters …

  5. Example • Growth of the springtail Folsomia candida • parthenogenetic animal (so clones) • data analysed in Jager et al 2004 (ES&T) • Simple growth model:

  6. Control growth • Fixed: f = 1 and L0 = 0.12 mm • Fitted: rB and Lm for each animal

  7. Control growth • Fixed: f = 1 and L0 = 0.12 mm • Fitted: rB and Lm for each animal 0.7 0.07 rB Lm 0.69 0.065 0.68 0.67 0.06 0.66 0.055 0.65 0.64 0.05 0.63 0.62 0.045 0.61 0.6 0.04 mean indiv. mean indiv.

  8. Adding cadmium • Exposed individuals grow to smaller size … • because they experience an effect on f ? • or, because they accidentally have a lower Lm?

  9. Adding cadmium • Exposed individuals grow to smaller size … • because they experience an effect on f ? • or, because they accidentally have a lower Lm? For an individual in a treatment, we cannot know its control response!

  10. Adding cadmium • Exposed individuals grow to smaller size … • because they experience an effect on f ? • or, because they accidentally have a lower Lm? • Practical approach: • fit rB and Lm for each individual … but • control distribution of rB and Lm as multivariate prior • force same treatment effect on all individuals …

  11. Effects of cadmium • First-order one-compartment toxicokinetics (scaled) • linear-with-threshold effect on f • Three parameters: ke, c0 and cT

  12. Effects of cadmium meta-optimisation , global parameters (ke, c0, cT) individual 3 individual 3 individual 3 individual 3 individual 2 individual 1 optimisation individual (rB1, Lm1)

  13. Effects of cadmium

  14. Effects of cadmium

  15. Effects of cadmium 2 1.8 ke 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 mean indiv.

  16. Concluding remarks I What have I learned? • Even with clones, individuals differ • causes bias in parameter estimates • bias increases with increasing variation … • Inter-individual differences can be included … but: • extremely calculation-intensive • requires good quality data for each individual • statistical method can/should be refined …

  17. Concluding remarks II This is “proof of concept”, next: • more endpoints simultaneously • more complete DEB models … primary parameters • but not too complex … “DEBkiss”: • no reserve, no maturity, simple embryonic rules

  18. Concluding remarks II This is “proof of concept”, next: • more endpoints simultaneously • more complete DEB models … primary parameters • but not too complex … “DEBkiss”: • no reserve, no maturity, simple embryonic rules • more extreme variation between individuals • Alpar Barsi on the pond snail …

  19. See my poster DEBkiss: The quest for the simplest energy-budget model More information on DEBtox/GUTS: http://www.debtox.info on DEB: http://www.bio.vu.nl/thb Courses Summercourse TKTD modelling Denmark 2013 (survival)

  20. Results

  21. DEBkiss

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