SAEM and FOCEi stabilization

A comprehensive collection of non-linear mixed effect (nlme) model algorithms:

• First Order Conditional Estimate (FOCE)

## eg
nlmixr(modelfn, data, "foce");

• First Order Conditional Estimate with interaction (FOCEi),

## eg
nlmixr(modelfn, data, "focei");

• Adaptive Gaussian quadrature (with Laplacian approximation as a special case see glmm and glmm2),
• Stochastic Approximation Estimation-Maximization (SAEM).

## eg
nlmixr(modelfn, data, "saem")

• Traditional R nlme

## eg
nlmixr(modelfn, data, "nlme")

Other features

• A minimalist, intuitive, expressive, and domain-specific nlme modeling language.
• The capability of joint modeling of multiple endpoints.
• A revamped SAEM engine with improved speed and stability.
• The capability of out-of-box Visual Predictive Checks (VPC) after a model fit.
• The capability of out-of-box sophisticated Clinical Trial Simulation (CTS) after a model fit.
• The capability of an out-of-box comprehensive diagnostic kit with a direct hook to xpose after a model fit.
• The capability of modeling “odd type” data, including binary data, count data, and bounded clinical endpoint (e.g., ADAS-cog has a range of 0 to 70).
• Parallel computing ODE solving via the openmp package -- an industry's first among the current population PK/PD simulators to the best of our knowledge.
• An intuitive, powerful, graphic user interface (GUI) based project manager in shinyMixR.

New in this release

This addresses a few stablitily fixes in the last release

• SAEM FOCEi objective function was fixed
• Standard Errors on FOCEi are more reasonable