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27 28 These models are flexible parametric models that have advantages over Cox regression 29 as the baseline cumulative hazard function is explicitly modelled with restricted cubic splines.
Figure 1 shows the time trend in the total prevalence of non-chromosomal NTD for the period 1991-2011, using pooled data from all of the EUROCAT registries included in the study and with time trends modelled with restricted cubic splines.
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Non-linear associations of diabetes risk with BMI and WC were also modelled using restricted cubic splines with sex-specific distribution-based knots at the 5th, 25th, 50th, 75th and 95th percentiles of BMI and WC.
Estimated date of seroconversion was continuously modelled using restricted cubic splines with knots at the 5th, 50th and 95th percentiles.
Calendar time was also modelled using restricted cubic splines in order to explore a nonlinear relationship with the outcome.
Continuous variables (age and ICNARC Physiology Score) were modelled using restricted cubic splines to allow for a flexible, nonlinear relationship between variables [ 21].
Duration will be flexibly modelled using restricted cubic splines to describe any non-straight-line association and suggest a minimal duration needed to see an effect of CIMT.
Continuous predictors will be flexibly modelled using restricted cubic splines, that is, piecewise cubic functions that are smooth at the knots and restricted to be linear in the tails.
The frequency and interval of modelled strategies were restricted and simplified compared with day-to-day clinical practice and current guidance/recommendations.
This may place unrealistic assumptions about the material being modelled or restrict the application of continuum damage mechanics to materials without significant anisotropy.
Stem lesion length was modelled using generalised least-squares models fitted by restricted maximum likelihood (Pinheiro et al. 2014).
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