***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Entrainment of the circadian pacemaker to the light : dark cycle is necessary for rhythmic physiological functions to be appropriately timed over the 24-h day . Nonentrainment results in sleep , endocrine , and neurobehavioral impairments . Exposures to intermittent bright light pulses have been reported to phase shift the circadian pacemaker with great efficacy . Therefore , we tested the hypothesis that a modulated light exposure ( MLE ) with bright light pulses in the evening would entrain subjects to a light : dark cycle 1 h longer than their own circadian period ( τ ) . Twelve subjects underwent a 65-day inpatient study . Individual subject 's circadian period was determined in a forced desynchrony protocol . Subsequently , subjects were released into 30 longer-than-24-h days ( daylength of τ + 1 h ) in one of three light : dark conditions : ( i ) ≈25 lux ; ( ii ) ≈100 lux ; and ( iii ) MLE : ≈25 lux followed by ≈100 lux , plus two 45-min bright light pulses of ≈9,500 lux near the end of scheduled wakefulness . We found that lighting levels of ≈25 lux were insufficient to entrain all subjects tested . Exposure to ≈100 lux was sufficient to entrain subjects , although at a significantly wider phase angle compared with baseline . Exposure to MLE was able to entrain the subjects to the imposed sleep – wake cycles but at a phase angle comparable to baseline . These results suggest that MLE can be used to entrain the circadian pacemaker to non-24-h days . The implication s of these findings are important because they could be used to treat circadian misalignment associated with space flight and circadian rhythm sleep disorders such as shift-work disorder The circadian pacemaker is differentially sensitive to the re setting effects of retinal light exposure , depending upon the circadian phase at which the light exposure occurs . Previously reported human phase response curves ( PRCs ) to single bright light exposures have employed small sample sizes , and were often based on relatively imprecise estimates of circadian phase and phase re setting . In the present study , 21 healthy , entrained subjects underwent pre- and post-stimulus constant routines ( CRs ) in dim light ( approximately 2 - 7 lx ) with maintained wakefulness in a semi-recumbent posture . The 6.7 h bright light exposure stimulus consisted of alternating 6 min fixed gaze ( approximately 10 000 lx ) and free gaze ( approximately 5000 - 9000 lx ) exposures . Light exposures were scheduled across the circadian cycle in different subjects so as to derive a PRC . Plasma melatonin was used to determine the phase of the onset , offset , and midpoint of the melatonin profiles during the CRs . Phase shifts were calculated as the difference in phase between the pre- and post-stimulus CRs . The result ant PRC of the midpoint of the melatonin rhythm revealed a characteristic type 1 PRC with a significant peak-to-trough amplitude of 5.02 h. Phase delays occurred when the light stimulus was centred prior to the critical phase at the core body temperature minimum , phase advances occurred when the light stimulus was centred after the critical phase , and no phase shift occurred at the critical phase . During the subjective day , no prolonged ' dead zone ' of photic insensitivity was apparent . Phase shifts derived using the melatonin onsets showed larger magnitudes than those derived from the melatonin offsets . These data provide a comprehensive characterization of the human PRC under highly controlled laboratory conditions Purpose To examine the effects of a simulated dawn during the last 30 min of sleep on the subsequent dissipation of sleep inertia and changes in simulated work and physical performance . Methods Eight participants , who reported difficulty with morning waking , were administered in a r and om order to a control ( C ) and a dawn simulation ( DS ) trial ( starting 30 min prior to waking ) . Subjective ratings of sleep quality and alertness were obtained alongside measures of cognitive performance ( addition and reaction time tasks measured at 5 , 30 and 75 min after waking at habitual workday times ) . Physical performance was also measured 35 min after waking using a self-paced cycling protocol . Results After waking in DS , perceived sleep quality was 1.16 ± 0.89 ( p = 0.01 ) points higher compared with C. Ratings of alertness were significantly higher in DS than C throughout the testing period ( p = 0.04 ) . Cognitive performance improved in both trials as time awake increased ( p < 0.0005 ) . On average , participants completed a greater number of additions in DS compared with C ( 69.5 ± 15.3 vs 66.9 ± 16.7 , p = 0.03 ) . Reaction times were also faster in DS compared with C ( 0.81 ± 0.07 s vs 0.86 ± 0.06 s , p < 0.0005 ) . The self-paced time-trial was completed 21.4 s ( 4.7 % ) quicker in DS ( p = 0.07 ) . Conclusion These data provide the first evidence that light exposure during the last 30 min of habitual sleep can increase subjective alertness and improve both cognitive and physical performance after waking Melatonin increases sleepiness , decreases core temperature , and increases peripheral temperature in humans .  Melatonin may produce these effects by activating peripheral receptors or altering autonomic activity . The latter hypothesis was investigated in 16 supine subjects . Three conditions were created by using bright light and exogenous melatonin : normal endogenous , suppressed , and pharmacological melatonin levels . Data during wakefulness from 1.5 h before to 2.5 h after each subject 's estimated melatonin onset ( wake time + 14 h ) were analyzed . Respiratory sinus arrhythmia ( cardiac parasympathetic activity ) and preejection period ( cardiac sympathetic activity ) did not vary among conditions . Pharmacological melatonin levels significantly decreased systolic blood pressure [ 5.75 + /- 1.65 ( SE ) mmHg ] but did not significantly change heart rate . Suppressed melatonin significantly increased rectal temperature ( 0.27 + /- 0.06 degrees C ) , decreased foot temperature ( 1.98 + /- 0.70 degrees C ) , and increased sleep onset latency ( 5.53 + /- 1.87 min ) . Thus melatonin does not significantly alter cardiac autonomic activity and instead may bind to peripheral receptors in the vasculature and heart . Furthermore , increases in cardiac parasympathetic activity before normal nighttime sleep can not be attributed to the concomitant increase in endogenous melatonin STUDY OBJECTIVES Light can induce an acute alerting response in humans ; however , it is unknown whether the magnitude of this response is simply a function of the absolute illuminance of the light itself , or whether it depends on illuminance history preceding the stimulus . Here , we compared the effects of illuminance history on the alerting response to a subsequent light stimulus . DESIGN A r and omized , crossover design was used to compare the effect of two illuminance histories ( 1 lux vs. 90 lux ) on the alerting response to a 6.5-h 90-lux light stimulus during the biological night . SETTING Intensive Physiologic Monitoring Unit , Brigham and Women 's Hospital , Boston , MA . PARTICIPANTS Fourteen healthy young adults ( 6 F ; 23.5 ± 2.9 years ) . INTERVENTIONS Participants were administered two 6.5-h light exposures ( LE ) of 90 lux during the biological night . For 3 days prior to each LE , participants were exposed to either 1 lux or 90 lux during the wake episode . MEASUREMENTS AND RESULTS The alerting response to light was assessed using subjective sleepiness ratings , lapses of attention , and reaction times as measured with an auditory psychomotor vigilance task , as well as power density in the delta/theta range of the waking EEG . The alerting response to light was greater and lasted longer when the LE followed exposure to 1 lux compared to 90 lux light . CONCLUSION The magnitude and duration of the alerting effect of light at night depends on the illuminance history and appears to be subject to sensitization and adaptation Jet lag is caused by a misalignment between circadian rhythms and local destination time . As humans typically take longer to re-entrain after a phase advance than a phase delay , eastward travel is often more difficult than westward travel . Previous strategies to reduce jet lag have focused on shaping the perceived light-dark cycle after arrival , in order to facilitate a phase shift in the appropriate direction . Here we tested treatments that travelers could use to phase advance their circadian rhythms prior to eastward flight . Thus , travelers would arrive with their circadian rhythms already partially re-entrained to local time . We determined how far the circadian rhythms phase advanced , and the associated side effects related to sleep and mood .  Twenty-eight healthy young subjects participated in 1 of 3 different treatments , which all phase advanced each subject 's habitual sleep schedule by 1 h/day for 3 days . The 3 treatments differed in morning light exposure for the 1st 3.5 h after waking on each of the 3 days : continuous bright light ( > 3000 lux ) , intermittent bright light ( > 3000 lux , 0.5 h on , 0.5 off , etc . ) , or ordinary dim indoor light ( < 60 lux ) . A phase assessment in dim light ( < 10 lux ) was conducted before and after the treatments to determine the endogenous salivary dim light melatonin onset ( DLMO ) . The mean DLMO phase advances in the dim , intermittent , and continuous light groups were 0.6 , 1.5 , and 2.1 h , respectively . The intermittent and continuous light groups advanced significantly more than the dim light group ( p < 0.01 ) but were not significantly different from each other . The side effects as assessed with actigraphy and logs were small . A 2-h phase advance may seem small compared to a 6- to 9-h time zone change , as occurs with eastward travel from the USA to Europe . However , a small phase advance will not only reduce the degree of re-entrainment required after arrival , but may also increase postflight exposure to phase-advancing light relative to phase-delaying light , thereby reducing the risk of antidromic re-entrainment . More days of preflight treatment could be used to produce even larger phase advances and potentially eliminate jet lag Background The purpose of the present study is to investigate effects of tryptophan intake and light exposure on melatonin secretion and sleep by modifying tryptophan ingestion at breakfast and light exposure during the daytime , and measuring sleep quality ( by using actigraphy and the OSA sleep inventory ) and melatonin secretion at night . Methods Thirty three male University students ( mean ± SD age : 22 ± 3.1 years ) completed the experiments lasting 5 days and 4 nights . The subjects were r and omly divided into four groups : Poor*Dim ( n = 10 ) , meaning a tryptophan-poor breakfast ( 55 mg/meal ) in the morning and dim light environment ( < 50 lx ) during the daytime ; Rich*Dim ( n = 7 ) , tryptophan-rich breakfast ( 476 mg/meal ) and dim light environment ; Poor*Bright ( n = 9 ) , tryptophan-poor breakfast and bright light environment ( > 5,000 lx ) ; and Rich*Bright ( n = 7 ) , tryptophan-rich breakfast and bright light .  Results Saliva melatonin concentrations on the fourth day were significantly lower than on the first day in the Poor*Dim group , whereas they were higher on the fourth day in the Rich*Bright group . Creatinine-adjusted melatonin in urine showed the same direction as saliva melatonin concentrations . These results indicate that the combination of a tryptophan-rich breakfast and bright light exposure during the daytime could promote melatonin secretion at night ; further , the observations that the Rich*Bright group had higher melatonin concentrations than the Rich*Dim group , despite no significant differences being observed between the Poor*Dim and Rich*Dim groups nor the Poor*Bright and Rich*Bright groups , suggest that bright light exposure in the daytime is an important contributor to raised melatonin levels in the evening . Conclusions This study is the first to report the quantitative effects of changed tryptophan intake at breakfast combined with daytime light exposure on melatonin secretion and sleep quality . Evening saliva melatonin secretion changed significantly and indicated that a tryptophan-rich breakfast and bright light exposure during the daytime promoted melatonin secretion at this time Light exposure can influence sleep and circadian timing , both of which have been shown to influence weight regulation . The goal of this study was to evaluate the relationship between ambient light , sleep and body mass index .  Participants included 54 individuals ( 26 males , mean age 30.6 , SD = 11.7 years ) .  Light levels , sleep midpoint and duration were measured with wrist actigraphy ( Actiwatch-L ) for 7 days . BMI was derived from self-reported height and weight . Caloric intake was determined from 7 days of food logs . For each participant , light and activity data were output in 2 minute epochs , smoothed using a 5 point ( 10 minute ) moving average and then aggregated over 24 hours . The mean light timing above 500 lux ( MLiT500 ) was defined as the average clock time of all aggregated data points above 500 lux . MLiT500 was positively correlated with BMI ( r = 0.51 , p<0.001 ) , and midpoint of sleep ( r = 0.47 , p<0.01 ) . In a multivariable linear regression model including MLiT500 and midpoint of sleep , MLiT500 was a significant predictor of BMI ( B = 
    Output:
    
Broad trends emerged suggesting that ( 1 ) bright light ( > 1000 lux ) has positive implication s for objective ly assessed sleep outcomes compared to dim ( < 100 lux ) and moderate light ( 100‐1000 lux ) and ( 2 ) bright light ( > 1000 lux ) has positive implication s for subjectively assessed sleep outcomes compared to moderate light ( 100‐1000 lux ) .
Effects due to the amount of light are moderated by the timing of light exposure such that , for objective ly assessed sleep outcomes , brighter morning and evening light exposure are consistent with a shift in the timing of the sleep period to earlier and later in the day , respectively .
For subjectively assessed sleep outcomes , brighter light delivered in the morning was associated with self‐reported sleep improvements and brighter evening light exposure was associated with worse self‐reported sleep