Effect of drugs O and C on APD prolongation.

<p><b>A:</b> simulated action potentials of the mouse ventricular model for the epicardial and endocardial cells. Pacing rate was 1 Hz. Relative APD prolongation normalized to the maximum prolongation with I_Ktof completely blocked was determined at various drug concentrations for drug O (○) and drug C (▪) on <b>B:</b> endocardium and <b>C:</b> Epicardium. Pacing rate was 1 Hz.</p

Dose dependent blockade of I_Ktof.

<p>The effect of various concentrations of drug on the action potential for <b>A:</b> open state block, and <b>B:</b> closed state block. The degree of block was determined by holding at −70 mV, the applying a test pulse to +50 mV for 500 ms. <b>C:</b> Open state binding of Drug O. <b>D:</b> Closed state binding of Drug C. Change in peak (▪), change in total current flow (○). Solid lines are Boltzmann fits to the data .</p

Comparison of action potentials at with S1S2 interval at 40 ms.

<p>Endocardium was stimulated at <b>A:</b> 1 Hz <b>B:</b> 10 Hz. Epicardium was stimulated at <b>C:</b> 1 Hz <b>D:</b> 10 Hz. Control, in the absence of drug is indicated by solid black line. Drug C is shown in blue, and drug O in red.</p

Example of APs recorded with different S1–S2 intervals.

<p>The first AP (control) represents the last beat of the pacing train at a cycle length of 1s (S1) on endocardial cells. APs are shown for S1–S2 intervals of 60, 100, 200, and 300 ms. Peak amplitudes are shown above the AP. APD30 is 4.89 ms, 8.17 ms, 6.11 ms, 5.58 ms, and 5.56 ms; APD75 is 18.11 ms, 22.07 ms, 18.65 ms, 17.81 ms, and 17.81 ms; and APD90 is 29.82 ms, 32.73 ms, 30.13 ms, 29.54 ms, and 29.47 ms for control, 60, 100, 200, and 300 ms S1–S2 intervals respectively.</p

Relative APD-BCL relationships.

<p><b>A:</b> endocardium and <b>B:</b> epicardium. (i) APD 30; (ii) APD75; (iii) APD90. Simulations are with 0.1 mM drug C (•), 1 mM drug C (▴), 0.1 mM drug O (○), 1 mM drug O (Δ). All APDs are normalized for control in the absence of drug.</p

Restitution curves for epicardial cells.

<p><b>A:</b> 1 Hz pacing; <b>B:</b> 2 Hz pacing; <b>C:</b> 10 Hz pacing. Top: APD30; Middle: APD75; Bottom: APD30. Control in the absence of drug (▪), 0.1 mM drug C (•), 1 mM drug C (▴), 0.1 mM drug O (○), 1 mM drug O (Δ).</p

APD-BCL relationships.

<p><b>A:</b> endocardium and <b>B:</b> epicardium. (i) APD 30; (ii) APD75; (iii) APD90. Control in the absence of drug (▪), 0.1 mM drug C (•), 1 mM drug C (▴), 0.1 mM drug O (○), 1 mM drug O (Δ).</p

Comparison of action potentials from endocardium and epicardium at fast and slow pacing rates.

<p>Endocardium: <b>A:</b> 200 ms <b>B:</b> 2s. Epicardium: <b>C:</b> 200 ms <b>D:</b> 2 s. Control is solid black line. Drug O is red, drug C blue.</p

Clinical trial interventions and associated costs and effects considered in HIV transmission simulation model.

<p>Uniform distributions were used for all costs and lognormal distribution for all effects in probabilistic analyses. Intervention costs were derived from India-specific sources.[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184179#pone.0184179.ref035" target="_blank">35</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184179#pone.0184179.ref049" target="_blank">49</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184179#pone.0184179.ref051" target="_blank">51</a>] Cost in 2012 USD.</p

Efficient frontier for HIV interventions during a 20-year simulation of HIV epidemic in Maharashtra, India.

<p>a, Graphical representation efficient frontier for all permutations of 12 interventions (4096 total combinations). Blue circles represent packages of interventions on the frontier, red represent packages off the frontier. b, focused graphical representation of efficient frontier for the lower end of discounted cost (0.888–0.898 Billion USD). c, Interventions contained within each efficient frontier package.</p