***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: OBJECTIVES To inform the debate over whether human sleep can be chronically reduced without consequences , we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation . DESIGN The chronic sleep restriction experiment involved r and omization to one of three sleep doses ( 4 h , 6 h , or 8 h time in bed per night ) , which were maintained for 14 consecutive days . The total sleep deprivation experiment involved 3 nights without sleep ( 0 h time in bed ) . Each study also involved 3 baseline ( pre-deprivation ) days and 3 recovery days . SETTING Both experiments were conducted under st and ardized laboratory conditions with continuous behavioral , physiological and medical monitoring . PARTICIPANTS A total of n = 48 healthy adults ( ages 21 - 38 ) participated in the experiments . INTERVENTIONS Noctumal sleep periods were restricted to 8 h , 6 h or 4 h per day for 14 days , or to 0 h for 3 days . All other sleep was prohibited . RESULTS Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days result ed in significant cumulative , dose-dependent deficits in cognitive performance on all tasks . Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days , and did not significantly differentiate the 6 h and 4 h conditions . Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis -- displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights . Comparison of chronic sleep restriction to total sleep deprivation showed that the latter result ed in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost . A statistical model revealed that , regardless of the mode of sleep deprivation , lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h ( s.e . 0.73 h ) . CONCLUSIONS Since chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation , it appears that even relatively moderate sleep restriction can seriously impair waking neurobehavioral functions in healthy adults . Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits , which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign . Physiological sleep responses to chronic restriction did not mirror waking neurobehavioral responses , but cumulative wakefulness in excess of a 15.84 h predicted performance lapses across all four experimental conditions . This suggests that sleep debt is perhaps best understood as result ing in additional wakefulness that has a neurobiological " cost " which accumulates over time In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias A telephone survey was conducted of a r and om sample of New York State licensed drivers to determine the prevalence and circumstances of  drowsy driving .  Based on the survey responses , 54.6 % of the drivers had driven while drowsy within the past year ; 22.6 % had ever fallen asleep at the wheel without having a crash , 2.8 % had ever crashed when they fell asleep , and 1.9 % had crashed when driving while drowsy . Of the reported crashes due to driving while drowsy or falling asleep at the wheel , 82.5 % involved the driver alone in the vehicle , 60.0 % occurred between 11:00 p.m. and 7:00 a.m. 47.5 % were drive-off-road crashes , and 40.0 % occurred on a highway or expressway . Multiple regression analysis suggested that the following driver variables are predictive of an increased frequency of driving drowsy : demographic characteristics ( younger drivers , more education , and men ) ; sleep patterns ( fewer hours of sleep at night and greater frequency of trouble staying awake during the day ) ; work patterns ( greater frequency of driving for job and working rotating shifts ) ; and driving patterns ( greater number of miles driven annually and fewer number of hours a person can drive before becoming drowsy ) In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted During long and monotonous driving at night , most drivers progressively show signs of visual fatigue and loss of vigilance . Their capacity to maintain adequate driving performance usually is affected and varies with the age of the driver . The main question is to know , on one h and , if occurrence of fatigue and drowsiness is accompanied by a modification in the driving performance of the driver and , on the other h and , if this relationship partially depends on the driver 's age . Forty-six male drivers , divided into three age categories : 20 - 30 , 40 - 50 , and 60 - 70 years , performed a 350-km motorway driving session at night on a driving simulator .  Driving errors were measured in terms of number of running-off-the-road incidents ( RORI ) and large speed deviations . The evolution of physiological vigilance level was evaluated using electroencephalography ( EEG ) recording . In older drivers , in comparison with young and middle-aged drivers , the degradation of driving performance was correlated to the evolution of lower frequency waking EEG ( i.e. , theta ) . Contrary to young and middle-aged drivers , the deterioration of the vigilance level attested by EEG correlated with the increase in gravity of all studied driving errors in older drivers . Thus , depending on the age category considered , only part of the driving errors would constitute a relevant indication as for the occurrence of a state of low arousal We ran a r and omized cross-over design study under  sleep-deprived and non-sleep-deprived driving conditions to test the effects of sleep restriction on real driving performance . The study was performed in a sleep laboratory and on an open French highway . Twenty-two healthy male subjects ( age = 21.5 + /- 2 years ; distance driven per year = 12,225 + /- 4739 km ( 7641 + /- 2962 miles ) [ mean + /- S.D. ] ) drove 1000 km ( 625 miles ) over 10 h during five 105 min sessions on an open highway . Self-rated fatigue and sleepiness before each session , number of inappropriate line crossings from video recordings and simple reaction time ( RT ) were measured . Total crossings increased after sleep restriction ( 535 crossings in the sleep-restricted condition versus 66 after non-restricted sleep ( incidence rate ratio ( IRR ) : 8.1 ; 95 % confidence interval ( 95 % CI ) : 3.2 - 20.5 ; p < 0.001 ) ) , from the first driving session . The interaction between the two factors ( conditionxtime of day ) was also significant ( F(5 , 105 ) = 3.229 ; p < 0.05 ) . Increasing sleepiness score was associated with increasing crossings during the next driving session in the sleep-restricted ( IRR : 1.9 ; 95 % CI : 1.4 - 2.4 ) but not in the non-restricted condition ( IRR : 1.0 ; 95 % CI : 0.8 - 1.3 ) . Increasing self-perceived fatigue was not associated with increasing crossings in either condition ( IRR : 0.95 ; 95 % CI : 0.93 - 0.98 and IRR : 1.0 ; 95 % CI : 0.98 - 1.02 ) . Rested subjects drove 1000 km with four shorts breaks with only a minor performance decrease . Sleep restriction induced important performance degradation even though time awake ( 8h ) and session driving times ( 105 min ) were relatively short . Major inter-individual differences were observed under sleep restriction . Performance degradation was associated with sleepiness and not fatigue . Sleepiness combined with fatigue significantly affected RT . Road safety campaigns should encourage drivers to avoid driving after sleep restriction , even on relatively short trips especially if they feel sleepy A novel task , combining simulated driving with subtraction , was compared in 26 participants ages 18 to 26 years ( M = 20.6 , SD = 2.3 ; 13 men ) . After two nights of 8.5 hr . in bed , participants performed a 30-min . driving and subtraction task followed by a 10-min . Psychomotor Vigilance Task . These tasks were repeated after two more nights of 8.5 hr . time in bed for the control group and 5 hours and 3 hours time in bed for the restricted group . The sensitivity of the task to moderate sleep loss was supported because impairment was seen on several dual-task variables whereas impairment was not observed on the Psychomotor Vigilance Task This article introduces the approach of GRADE to rating  quality of evidence .  GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence In industrialized countries one-fifth of all traffic accidents can be ascribed to sleepiness behind the wheel . Driver sleepiness can have many causes , including the use of medicinal drugs or prolonged driving . The present study compared the effects of prolonged highway driving at night with driving impairment caused by alcohol . A cross-over balanced design tested 14 healthy young men who drove three sessions during night-time on the open road .  The driving sessions were of 2 , 4 and 8 h ( 03:00 - 05:00 , 01:00 - 05:00 and 21:00 - 05:00 hours ) duration . St and ard deviation of lateral position ( SDLP , cm ) , measuring the weaving of the car in the last driving hour of each session , was the primary parameter . Only 2 h of continuous nocturnal driving were sufficient to produce driving impairment comparable to a blood alcohol concentration ( BAC ) of 0.05 % ; after 3 h of driving impairment corresponds to a BAC of 0.08 % . In conclusion , a maximum of two continuous nocturnal driving hours should be recommended Slowed eyelid closure coupled with increased duration and frequency of closure is associated with drowsiness . This study assessed the utility of two devices for automated measurement of slow eyelid closure in a st and ard poor performance condition ( alcohol ) and following 12-h sleep deprivation . Twenty-two healthy participants ( mean age=20.8 ( SD 1.9 ) years ) with no history of sleep disorders participated in the study . Participants underwent one baseline and one counterbalanced session each over two weeks ; one 24-hour period of sleep deprivation , and one daytime session during which alcohol was consumed after a normal night of sleep . Participants completed a test battery consisting of a 30-min simulated driving task , a 10-min Psychomotor Vigilance Task ( PVT ) and the Karolinska Sleepiness Scale ( KSS ) each in two baseline sessions , and in two r and omised , counterbalanced experimental sessions ; following sleep deprivation and following alcohol consumption . Eyelid closure was measured during both tasks using two automated devices ( Copilot and Optalert ™ ) . There was an increase in the proportion of time with eyelids closed and the Johns Drowsiness Score ( incorporating relative velocity of eyelid movements ) following sleep deprivation using Optalert ( p<0.05 for both ) . These measures correlated significantly with crashes , PVT lapses and subjective sleepiness ( r-values 0.46 - 0.69 , p<0.05 ) . No difference between the two sessions for PERCLOS recorded during the PVT or the driving task as measured by the Cop 
    Output:
    
While speed-related outcomes and crash events ( also with very low- quality evidence ) both increased under chronic sleep loss , discrepant findings were reported under conditions of acute total sleep deprivation .