Circadian testing protocol.

<p>The flowchart identifies the order of measurements conducted each hour during the 24 h test period.</p

Diurnal cone photoreceptor contributions to the human pupil light reflex.

<p>(A) Baseline pupil diameter of 11 participants (mean ± s.e.m) viewing a uniform photopic screen, recorded over 20–24 hours (linear model, line R²>1.00). (B) Average maximum pupil constriction (488 nm) for 11 participants (±s.e.m) analysed as for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017860#pone-0017860-g001" target="_blank">Fig. 1A</a>. Insets; Coloured lines show baseline pupil diameter (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017860#pone-0017860-g001" target="_blank">Fig. 1A</a>) and maximum constriction of one participant (19,F) at circadian times of 3.5 h and 15.4 h (from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017860#pone-0017860-g002" target="_blank">Fig. 2A</a>). Lines show linear regression; R²>0.47. (C) Average maximum pupil constriction (610 nm) for 11 participants (± s.e.m). Direct outer retinal cone photoreceptor contributions to the pupil do not vary diurnally (R²>0.64).</p

Circadian variation of the ipRGC controlled post-illumination pupil response of the pupil light reflex.

<p>Left and right columns show pupil light reflex data for two participants (19yo F, 18yo M). Left ordinates show pupil diameter (% baseline), right ordinates show pupil diameter (mm). (A) Post-illumination pupil responses at three circadian times were 75.0% (3.5 h), 83.2% (9.4 h) and 92.5% (15.4 h) of the mean baseline pupil diameter of 7.77 mm. The pupil light reflex (thin lines) was described by best-fitting linear and exponential functions (thick lines). (B) Post-illumination pupil responses of 71.4% (5.4 h), 77.0% (10.4 h) and 99.6% (15.4 h) of the mean baseline pupil diameter of 6.68 mm. (C) The post-illumination component of the pupil light reflex fitted with a skewed baseline cosine function (Eq 1) (data show mean ± s.d; filled circles; model, line) (R² = 079). (D) As for panel (C) for participant 2 (18 yo M) (R² = 0.71). Post-illumination pupil response (blue lines) from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017860#pone-0017860-g002" target="_blank">Figure 2B</a> at 5.4 h and 15.4 h. Insets in panel (C) and (D) show the post-illumination pupil response (blue lines) from panel (A) at 3.5 and 15.4 h.</p

Search statements and limiters and number of papers identified from each database.

<p>Search statements and limiters and number of papers identified from each database.</p

Comparison of the circadian response of intrinsic ipRGC and cone inputs to the post-illumination pupil response (PIPR) with salivary melatonin.

<p>Symbols (n = 11 participants; mean ± s.e.m) and lines (mean skewed baseline cosine function; Eq 1) encode intrinsic ipRGC (blue) and cone inputs (red) to the ipRGC controlled PIPR and salivary melatonin (black). Arrows indicate threshold change in activity based on the group model. (A) PIPR diameter (488 nm stimulus) began to increase at 10:50 h and peaked at 14:58 h (blue arrows) (R² = 0.65). (B) PIPR diameter (688 nm stimulus) began to increase at 9:16 h and peaked at 15:18 h (red arrows) (R² = 0.80). (C) Salivary melatonin began to increase at 13:30 h and peaked at 18:40 circadian hours (red arrows) (R² = 0.96), 2:40 hours after PIPR (488 nm) began to increase. For the best-fitting salivary melatonin curve (Eq 1), <i>(b)</i> = 4.54 pM; peak amplitude above baseline <i>(H)</i> = 65.40 pM; width <i>(c)</i> = −0.091; phase <i>(Φ)</i> = 11.46 radians and skewness <i>(v)</i> = 0.302. (D) Re-dilation kinetics (mm.s⁻¹) derived from the time-constant of the best-fitting exponential functions to the 488 nm PIPR. (E) Re-dilation kinetics (mm.s⁻¹) for the 610 nm PIPR. Change in post-illumination pupil response amplitude and kinetics independent of the constant external illumination demonstrates circadian control of ipRGC activity.</p

Inclusion criteria and exclusion conditions for selecting papers for systematic review.

<p>Inclusion criteria and exclusion conditions for selecting papers for systematic review.</p

Summary of key methodological characteristics and findings of individual papers.

<p>Summary of key methodological characteristics and findings of individual papers.</p

Ranking of the quality of the body of evidence for each driving performance outcome measure.

<p>Ranking of the quality of the body of evidence for each driving performance outcome measure.</p

Distribution of papers based on their methodological elements.

<p>Distribution of papers based on their methodological elements.</p

Flow diagram of systematic review based on PRISMA 2009.

<p>Flow diagram of systematic review based on PRISMA 2009.</p