Can't get Mathematica to simplify an expression

A few things of note:

  1. Like @m_goldberg suggested, it is wise to explicitly state d ∈ Reals, s ∈ Reals.
  2. Because you introduced .'s after your numbers, you force mathematica to treat your integers as floats, which introduces rounding errors, removing these helps.
  3. Simplification introduces absolutes variable epxressions, taking these to be positive or negative helps.

Positive:

FullSimplify[expr, 
 Assumptions -> {d ∈ Reals, 
   s ∈ 
    Reals, -6 d^2 + 
     16 d^3 + (1 + Sqrt[8 d^2 + (1 - 2 s)^2] - 2 s) (-1 + 2 s) - 
     4 d (1 + Sqrt[8 d^2 + (1 - 2 s)^2] - 2 s) (-1 + 2 s) > 0}]

$$\frac{1+\sqrt{8d^2+\left(1-2s\right)^2}-2s}{2\sqrt{8d^2+\left(1-2s\right)^2}}$$

Negative:

FullSimplify[expr, 
 Assumptions -> {d ∈ Reals, 
   s ∈ 
    Reals, -6 d^2 + 
     16 d^3 + (1 + Sqrt[8 d^2 + (1 - 2 s)^2] - 2 s) (-1 + 2 s) - 
     4 d (1 + Sqrt[8 d^2 + (1 - 2 s)^2] - 2 s) (-1 + 2 s) < 0}]

$$\begin{cases} -1 & \left(1+4d\right)\left(1+\sqrt{8d^{2}+\left(1-2s\right)}-2s\right)\left(-1+2s\right)\ge2d^{2}\left(3+8d\right)\\ \frac{2d\left(d-sd^{2}+2\left(1+\sqrt{8d^{2}+\left(1-2s\right)^{2}}\right)\right)\left(-1+2s\right)}{-8d^{2}+\left(1+\sqrt{8d^{2}+\left(1-2s\right)^{2}}-2s\right)\left(-1+2s\right)} & Else \end{cases}$$

Yielding an in total 3 cases environment.


Following from your expression expr:

exact = Rationalize[expr]

vars = Variables[expr]

Refine[exact, Element[vars, Reals]]

Simplify[%, Element[vars, Reals]]

(* substitution picked by me and copy-pasted from the last output *)
% /. Sqrt[8 d^2 + (1 - 2 s)^2] -> x1

(* another such substitution *)    
% /. (1 - 2 s + x1) -> x2

enter image description here


Just one approach, and not necessarily the kind of result you want:

expr  (* your expression *)

FullSimplify[Rationalize[%], Variables[%] ∈ Reals];
out = Experimental`OptimizeExpression[%];

new = Symbol /@ CharacterRange[63396, 63421];
old = DeleteDuplicates@Cases[out, s_Symbol /; Context[s] === "Compile`", {-1}]

Extract[out, {1, 2}, Defer] /.
  Cases[Flatten[{old, new}, {2}], {o_, n_} :> (o :> n)]

enter image description here