Accident Case Study Delayed Reaction To Bed

1. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness Scale. Sleep (1991) 14:50–5. [PubMed]

2. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res (1989) 28:193–213.10.1016/0165-1781(89)90047-4 [PubMed][Cross Ref]

3. Pagani L, Semenova EA, Moriggi E, Revell VL, Hack LM, Lockley SW, et al. The physiological period length of the human circadian clock in vivo is directly proportional to period in human fibroblasts. PLoS One (2010) 10:e13376.10.1371/journal.pone.0013376 [PMC free article][PubMed][Cross Ref]

4. Bell-Pedersen D, Cassone VM, Earnest DJ, Golden SS, Hardin PE, Thomas TL, et al. Circadian rhythms from multiple oscillators: lessons from diverse organisms. Nat Rev Genet (2005) 7:544–56.10.1038/nrg1633 [PMC free article][PubMed][Cross Ref]

5. Albrecht U. Timing to perfection: the biology of central and peripheral circadian clocks. Neuron (2012) 74(2):246–60.10.1016/j.neuron.2012.04.006 [PubMed][Cross Ref]

6. Golombek DA, Rosenstein RE. Physiology of circadian entrainment. Physiol Rev (2010) 90(3):1063–102.10.1152/physrev.00009.2009 [PubMed][Cross Ref]

7. Morin LP. Neuroanatomy of the extended circadian rhythm system. Exp Neurol (2013) 243:4–20.10.1016/j.expneurol.2012.06.026 [PMC free article][PubMed][Cross Ref]

8. Hattar S, Liao HW, Takao M, Berson DM, Yau KW. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science (2002) 295(5557):1065–70.10.1126/science.1069609 [PMC free article][PubMed][Cross Ref]

9. LeGates TA, Fernandez DC, Hattar S. Light as a central modulator of circadian rhythms, sleep and affect. Nat Rev Neurosci (2014) 15(7):443–54.10.1038/nrn3743 [PMC free article][PubMed][Cross Ref]

10. Mohawk JA, Green CB, Takahashi JS. Central and peripheral circadian clocks in mammals. Annu Rev Neurosci (2012) 35:445–62.10.1146/annurev-neuro-060909-153128 [PMC free article][PubMed][Cross Ref]

11. Reppert SM, Weaver DR. Coordination of circadian timing in mammals. Nature (2002) 418(6901):935–41.10.1038/nature00965 [PubMed][Cross Ref]

12. Sack RL, Auckley D, Auger RR, Carskadon MA, Wright KP, Jr, Vitiello MV, et al. Circadian rhythm sleep disorders: part I, basic principles, shift work and jet lag disorders. An American Academy of Sleep Medicine review. Sleep (2007) 30(11):1460–83. [PMC free article][PubMed]

13. Lockley SW. Overview of the circadian timekeeping system and diagnostic tools for circadian rhythm sleep disorders. In: Barkoukis TJ, Matheson JK, Ferber R, Doghrami K, editors. , editors. Therapy in Sleep Medicine. Philadelphia, PA: Saunders; (2012). p. 363–77.

14. Lahti T, Merikanto I, Partonen T. Circadian clock disruptions and the risk of cancer. Ann Med (2012) 8:847–53.10.3109/07853890.2012.727018 [PubMed][Cross Ref]

15. Kettner NM, Katchy CA, Fu L. Circadian gene variants in cancer. Ann Med (2014) 4:208–20.10.3109/07853890.2014.914808 [PMC free article][PubMed][Cross Ref]

16. Duffy JF, Cain SW, Chang AM, Phillips AJ, Münch MY, Gronfier C, et al. Sex difference in the near-24-hour intrinsic period of the human circadian timing system. Proc Natl Acad Sci U S A (2011) 108(Suppl 3):15602–8.10.1073/pnas.1010666108 [PMC free article][PubMed][Cross Ref]

17. Lockley S, Cohen D, Harper D, Uchiyama M. Other circadian rhythm disorders: non-24-hour sleep-wake disorder and irregular sleep-wake disorder. In: Barkoukis TJ, Matheson JK, Ferber R, Doghrami K, editors. , editors. Therapy in Sleep Medicine. Philadelphia, PA: Saunders; (2012). p. 411–24.

18. Sack RL, Lewy AJ, Blood ML, Keith LD, Nakagawa H. Circadian rhythm abnormalities in totally blind people: incidence and clinical significance. J Clin Endocrinol Metab (1992) 75(1):127–34.10.1210/jc.75.1.127 [PubMed][Cross Ref]

19. American Academy of Sleep Medicine. International Classification of Sleep Disorders: Diagnostic and Coding Manual. 3rd ed Darien, IL: American Academy of Sleep Medicine; (2014).

20. Auger RR, Burgess HJ, Emens JS, Deriy LV, Thomas SM, Sharkey KM. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: advanced sleep-wake phase disorder (ASWPD), delayed sleep-wake phase disorder (DSWPD), non-24-hour sleep-wake rhythm disorder (N24SWD), and irregular sleep-wake rhythm disorder (ISWRD). An update for 2015. J Clin Sleep Med (2015) 11(10):1199–236.10.5664/jcsm.5100 [PMC free article][PubMed][Cross Ref]

21. Uchiyama M, Lockley SW. Non-24-hour sleep-wake syndrome in sighted and blind patients. Sleep Med Clin (2009) 4:195–211.10.1016/j.jsmc.2009.02.002 [Cross Ref]

22. Lavedan C, Forsberg M, Gentile AJ. Tasimelteon: a selective and unique receptor binding profile. Neuropharmacology (2015) 91:142–7.10.1016/j.neuropharm.2014.12.004 [PubMed][Cross Ref]

23. Stahl SM. Mechanism of action of tasimelteon in non-24 sleep-wake syndrome: treatment for a circadian rhythm disorder in blind patients. CNS Spectr (2014) 19(6):475–8.10.1017/S1092852914000637 [PubMed][Cross Ref]

24. Boivin DB, James FO, Santo JB, Caliyurt O, Chalk C. Non-24-hour sleep-wake syndrome following a car accident. Neurology (2003) 60(11):1841–3.10.1212/01.WNL.0000061482.24750.7C [PubMed][Cross Ref]

25. O’Neill B, Gardani M, Findlay G, Whyte T, Cullen T. Challenging behaviour and sleep cycle disorder following brain injury: a preliminary response to agomelatine treatment. Brain Inj (2014) 28(3):378–81.10.3109/02699052.2013.865264 [PubMed][Cross Ref]

26. Achermann P, Borbély AA. Mathematical models of sleep regulation. Front Biosci (2003) 8:s683–93.10.2741/1064 [PubMed][Cross Ref]

27. Borbély AA. A two process model of sleep regulation. Hum Neurobiol (1982) 1(3):195–204. [PubMed]

28. Jones CR, Huang AL, Ptáček LJ, Fu YH. Genetic basis of human circadian rhythm disorders. Exp Neurol (2013) 243:28–33.10.1016/j.expneurol.2012.07.012 [PMC free article][PubMed][Cross Ref]

29. Reichert CF, Maire M, Gabel V, Viola AU, Kolodyazhniy V, Strobel W, et al. Insights into behavioral vulnerability to differential sleep pressure and circadian phase from a functional ADA polymorphism. J Biol Rhythms (2014) 29(2):119–30.10.1177/0748730414524898 [PubMed][Cross Ref]

30. Valomon A, Holst SC, Bachmann V, Viola AU, Schmidt C, Zürcher J, et al. Genetic polymorphisms of DAT1 and COMT differentially associate with actigraphy-derived sleep-wake cycles in young adults. Chronobiol Int (2014) 31(5):705–14.10.3109/07420528.2014.896376 [PubMed][Cross Ref]

31. Maire M, Reichert CF, Gabel V, Viola AU, Strobel W, Krebs J, et al. Sleep ability mediates individual differences in the vulnerability to sleep loss: evidence from a PER3 polymorphism. Cortex (2014) 52:47–59.10.1016/j.cortex.2013.11.008 [PubMed][Cross Ref]

32. Chellappa SL, Viola AU, Schmidt C, Bachmann V, Gabel V, Maire M, et al. Light modulation of human sleep depends on a polymorphism in the clock gene Period3. Behav Brain Res (2014) 271:23–9.10.1016/j.bbr.2014.05.050 [PubMed][Cross Ref]

33. Brown SA, Kunz D, Dumas A, Westermark PO, Vanselow K, Tilmann-Wahnschaffe A, et al. Molecular insights into human daily behavior. Proc Natl Acad Sci U S A (2008) 105(5):1602–7.10.1073/pnas.0707772105 [PMC free article][PubMed][Cross Ref]

34. Zhu L, Zee PC. Circadian rhythm sleep disorders. Neurol Clin (2012) 30(4):1167–91.10.1016/j.ncl.2012.08.011 [PMC free article][PubMed][Cross Ref]

35. Salas C, Pérez-Vera P, Frías S. Genetic abnormalities in leukemia secondary to treatment in patients with Hodgkin’s disease. Rev Invest Clin (2011) 1:53–63. [PubMed]

36. Katada S, Sassone-Corsi P. The histone methyltransferase MLL1 permits the oscillation of circadian gene expression. Nat Struct Mol Biol (2010) 12:1414–21.10.1038/nsmb.1961 [PubMed][Cross Ref]

37. Valekunja UK, Edgar RS, Oklejewicz M, van der Horst GT, O’Neill JS, Tamanini F, et al. Histone methyltransferase MLL3 contributes to genome-scale circadian transcription. Proc Natl Acad Sci U S A (2013) 4:1554–9.10.1073/pnas.1214168110 [PMC free article][PubMed][Cross Ref]

38. Gatfield D, Schibler U. Physiology. Proteasomes keep the circadian clock ticking. Science (2007) 316(5828):1135–6.10.1126/science.1144165 [PubMed][Cross Ref]

39. Blau J. PERspective on PER phosphorylation. Genes Dev (2008) 22(13):1737–40.10.1101/gad [PMC free article][PubMed][Cross Ref]

40. Hirota T, Lee JW, St John PC, Sawa M, Iwaisako K, Noguchi T, et al. Identification of small molecule activators of cryptochrome. Science (2012) 337(6098):1094–7.10.1126/science.1223710 [PMC free article][PubMed][Cross Ref]

41. Lee E, Kim EY. A role for timely nuclear translocation of clock repressor proteins in setting circadian clock speed. Exp Neurobiol (2014) 23(3):191–9.10.5607/en.2014.23.3.191 [PMC free article][PubMed][Cross Ref]

42. Etchegaray JP, Machida KK, Noton E, Constance CM, Dallmann R, Di Napoli MN, et al. Casein kinase 1 delta regulates the pace of the mammalian circadian clock. Mol Cell Biol (2009) 29(14):3853–66.10.1128/MCB.00338-09 [PMC free article][PubMed][Cross Ref]

43. Lee HM, Chen R, Kim H, Etchegaray JP, Weaver DR, Lee C. The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1. Proc Natl Acad Sci U S A (2011) 108(39):16451–6.10.1073/pnas.1107178108 [PMC free article][PubMed][Cross Ref]

44. Schmutz I, Wendt S, Schnell A, Kramer A, Mansuy IM, Albrecht U. Protein phosphatase 1 (PP1) is a post-translational regulator of the mammalian circadian clock. PLoS One (2011) 6(6):e21325.10.1371/journal.pone.0021325 [PMC free article][PubMed][Cross Ref]

45. Papp SJ, Huber AL, Jordan SD, Kriebs A, Nguyen M, Moresco JJ, et al. DNA damage shifts circadian clock time via Hausp-dependent Cry1 stabilization. Elife (2015) 4:e04883.10.7554/eLife.04883 [PMC free article][PubMed][Cross Ref]

46. Godinho SI, Maywood ES, Shaw L, Tucci V, Barnard AR, Busino L, et al. The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period. Science (2007) 316(5826):897–900.10.1126/science.1141138 [PubMed][Cross Ref]

47. Busino L, Bassermann F, Maiolica A, Lee C, Nolan PM, Godinho SI, et al. SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins. Science (2007) 316(5826):900–4.10.1126/science.1141194 [PubMed][Cross Ref]

48. Anand SN, Maywood ES, Chesham JE, Joynson G, Banks GT, Hastings MH, et al. Distinct and separable roles for endogenous CRY1 and CRY2 within the circadian molecular clockwork of the suprachiasmatic nucleus, as revealed by the Fbxl3(Afh) mutation. J Neurosci (2013) 17:7145–53.10.1523/JNEUROSCI.4950-12.2013 [PMC free article][PubMed][Cross Ref]

49. Vitaterna MH, Ko CH, Chang AM, Buhr ED, Fruechte EM, Schook A, et al. The mouse Clock mutation reduces circadian pacemaker amplitude and enhances efficacy of resetting stimuli and phase-response curve amplitude. Proc Natl Acad Sci U S A (2006) 103(24):9327–32.10.1073/pnas.0603601103 [PMC free article][PubMed][Cross Ref]

50. Hatori M, Gill S, Mure LS, Goulding M, O’Leary DD, Panda S. Lhx1 maintains synchrony among circadian oscillator neurons of the SCN. Elife (2014) 3:e03357.10.7554/eLife.03357 [PMC free article][PubMed][Cross Ref]

51. Bedont JL, LeGates TA, Slat EA, Byerly MS, Wang H, Hu J, et al. Lhx1 controls terminal differentiation and circadian function of the suprachiasmatic nucleus. Cell Rep (2014) 7(3):609–22.10.1016/j.celrep.2014.03.060 [PMC free article][PubMed][Cross Ref]

52. Yamaguchi Y, Suzuki T, Mizoro Y, Kori H, Okada K, Chen Y, et al. Mice genetically deficient in vasopressin V1a and V1b receptors are resistant to jet lag. Science (2013) 342(6154):85–90.10.1126/science.1238599 [PubMed][Cross Ref]

53. van Geijlswijk IM, Korzilius HP, Smits MG. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep (2010) 33(12):1605–14. [PMC free article]

Whether he was truly asleep at the wheel or just zoned out, Metro North train engineer William Rockefeller isn't the only shiftworker to find himself at the center of a fatal accident with reports of sleep deprivation. Regardless of the outcome of the investigation, the accident got us thinking about the many disasters that have a working corps suffering from a lack of sleep at the center.

Perhaps tragic accidents like this one -- and the global catastrophes outlined below -- can wake us up to the realities of skimping on sleep. The gravity of the following disasters -- combined with the near-misses at Davis-Besse Nuclear Power Station in Ohio and Peach Bottom Nuclear Reactor in Pennsylvania -- should serve as a reminder to all of us that sleep is utterly crucial.

In a 1988 study on the connection between sleep (or lack of it) and manmade catastrophes, a committee of researchers concluded that, in the examples cited below, "[i]t cannot be proved that the human responses and errors occurring in all or most of these incidents and accidents resulted from lowered alertness, inattention, or delayed reaction due to active, sleep-related processes. Yet, it appears to be more than coincidental that the serious accidents were made worse by inadequate human response at a time when other data reflect a diminished capacity to function effectively despite one's belief and best intentions. ... Sleep and sleep-related factors appear to be involved in widely disparate types of disasters."


When the nuclear power plant in Ukraine exploded, creating what some have described as the world's worst nuclear disaster, the engineers involved had been working for 13 hours or more, MSN reported. Two plant workers died that night. Nearly 240 people were originally diagnosed with radiation poisoning, and 134 cases were later confirmed. Of those confirmed cases, 28 people died during the following few weeks. The number of deaths attributed to the explosion over the next 15 years proved difficult to quantify. "In reality, the actual number
of deaths caused by this accident is unlikely ever to be precisely known," the World Health Organization wrote in a 2006 report.

Three Mile Island

Considered to be the most serious nuclear incident on U.S. soil, the accident at Three Mild Island in Pennsylvania was attributed to human error. Between 4 and 6 a.m. on March 28, 1979, shiftworkers didn't notice as the plant lost coolant, eventually resulting in the overheating of the reactor's core, according to the United States Nuclear Regulatory Commission. Officials discovered later than about half of the core had melted, yet there were minimal effects outside of the plant.

The Challenger Explosion

The space shuttle exploded just seconds after its January 1986 launch, killing all seven crew members. According to a 1988 report, certain managers involved in the launch had only slept two hours before arriving to work at 1 a.m. that morning. The Presidential Commission on the accident admitted the danger of this deprivation in its June 1986 report, writing, "The willingness of NASA employees in general to work excessive hours, while admirable, raises serious questions when it jeopardizes job performance, particularly when critical management decisions are at stake."

The Exxon Valdez Oil Spill

When the supertanker ran aground in Alaska in 1989, destroying wildlife and spilling 258,000 barrels of crude oil in the process, third mate Gregory Cousins was allegedly sleeping at the helm, leaving him unable to turn the boat back into the shipping lanes in time to avoid disaster. The crew had just put in a 22-hour shift loading the oil onto the ship, the Anchorage Daily News reported, and Cousins had reportedly only had a "catnap" in the last 16 hours leading up to the crash.

American Airlines Flight 1420 Crash

On June 1, 1999, American Airlines Flight 1420 overshot the runway at Little Rock National Airport, killing 11, including the captain, and injuring the first officer, the flight attendants and 105 passengers. Only 24 passengers were not injured. Severe thunderstorms played a role, but the National Transportation Safety Board also determined that "impaired performance resulting from fatigue" was involved.

CORRECTION: This article previously suggested incorrectly that sleep deprivation had been explicitly cited as a factor in the meltdown at Three Mile Island. Language has also been added to provide further context for the association between these disasters and lack of sleep.

One thought on “Accident Case Study Delayed Reaction To Bed

Leave a Reply

Your email address will not be published. Required fields are marked *