What this trial measures

• Circadian Phase14 days

  Saliva will be assayed for melatonin used standardized assays. Melatonin will be sampled at 1h intervals during wakefulness. Melatonin onset will be calculated using the linear interpolated time at which melatonin levels reach 25% of a fitted peak-to-trough amplitude.

• Energy Intake14 days

  Throughout the forced desynchrony protocol, participants will have ad libitum access to food, which will be scored using NDSR software. NDSR was developed to help plan, manage, and analyze food and nutrient intake. Each meal and set of snacks will be timestamped (midpoint of snack availability) and binned by circadian phase based on the individuals' melatonin and also by time awake.

• Energy Content14 days

  Throughout the forced desynchrony protocol, participants will have ad libitum access to food, which will be scored using NDSR software. NDSR was developed to help plan, manage, and analyze food and nutrient intake. Each meal and set of snacks will be timestamped (midpoint of snack availability) and binned by circadian phase based on the individuals' melatonin and also by time awake.

• Glucose Metabolism~3 days

  The participant's glucose and insulin response to a mixed meal diet high in carbohydrates may be tested up to 3 times during the protocol (Days 2, 4, and 13). Each participant will have a choice of 1 of 2 meal options and will be given that meal throughout the study. During this mixed meal test, a baseline blood draw will occur \~7-min before the meal and then the frequency of blood samples will increase to every 10-min after the meal for 90 min and then every 30 min for 90 min for a total of 14 samples (\~1 mL each, total of \~14 mL) over 180 minutes to measure glucose and hormone response in detail. Samples at each time point will be obtained for measurement of suppressibility of plasma free fatty acids. Blood will also be drawn every 4h during the protocol for 24h insulin and glucose.

• Resting energy expenditure14 days

  Resting energy expenditure will be measured upon awaking each protocol day via indirect calorimetry. Oxygen consumption and carbon dioxide production will be used to calculate metabolic rate.

• Resting energy macronutrient oxidation14 days

  Resting macronutrient oxidation will be measured upon awaking each protocol day via indirect calorimetry. Oxygen consumption and carbon dioxide production will be used to calculate the oxidation of carbohydrate and fat.

• Blood Pressure14 days

  Beat-to-beat blood pressure will be obtained using a non-invasive device employing the volume-clamp method with hydrostatic correction (Nexfin). Beat-to-beat blood pressure will be recorded 1) during each sleep episode and 2) each constant posture period following awakening. Both systolic and diastolic blood pressure will be measured.

• Heart Rate14 days

  For the duration of the study, 2 channels of EKG are recorded (RA-V6) and stored on BioPac recorders using Acqknowledge software (256 Hz).

• Sympathetic Activity14 days

  The investigators will use the high frequency power of the heart rate variability power spectrum to estimate cardiac parasympathetic activity (vagal tone) as modulated by respiratory sinus arrhythmia. RR interval data for sequential 5-minute time segments will be used for heart rate variability analysis according to published criteria. Frequency domain measures are calculated by interpolating the RR tachogram with a cubic spline and re-sampling. Power spectral density will be calculated using Welch's technique. Calculated time domain heart rate variability measures will include mean RR, SD of all normal-normal RR intervals, and a percentage of RR intervals differing by greater than 50 msec.

• Parasympathetic Activity14 days

  The investigators will use the high frequency power of the heart rate variability power spectrum to estimate cardiac parasympathetic activity (vagal tone) as modulated by respiratory sinus arrhythmia. RR interval data for sequential 5-minute time segments will be used for heart rate variability analysis according to published criteria. Frequency domain measures are calculated by interpolating the RR tachogram with a cubic spline and re-sampling. Power spectral density will be calculated using Welch's technique. Calculated time domain heart rate variability measures will include mean RR, SD of all normal-normal RR intervals, and a percentage of RR intervals differing by greater than 50 msec.

• Vascular Endothelial Function14 days

  The investigators will measure vascular endothelial function at various points throughout the protocol. Brachial or femoral artery flow-mediated dilation will be measured in the supine position.

• Leptin14 days

  The investigators will measure markers of hunger via the satiety hormone leptin. Blood will be assayed using our standard procedures approximately every six hours.

• Ghrelin14 days

  The investigators will measure markers of hunger via the hunger hormone ghrelin. Blood will be assayed using our standard procedures approximately every six hours.

• Endocannabinoids14 days

  The endocannabinoids 2-AG and AEA, as well as non-endocannabinoid N-acylethanolamines (N-oleoylethanolamine \[OEA\] and N-palmitoylethanolamine \[PEA\]), and 2-monoacylglycerols (2-oleoylglycerol \[2-OG\]) via blood. Blood will be assayed using our standard procedures approximately every six hours.

• Posture Test Blood Pressure14 days

  Standing up after a period of lying down is a large physiological challenge requiring sympathetic activation to maintain perfusion pressure to the brain and void syncope. Participants will be fitted with a 2 lead EKG, a finger cuff for non-invasive BP recordings on a beat-by-beat basis and a sphygmomanometer cuff on the other arm for manual assessment of BP \[for cross calibration and safety check\]. The finger cuffs will be placed on the non-dominant hand and held in place by an arm sling so that the BP cuffs will be at heart level. BP will be assessed while participants stand up from a semi-recumbent posture and remain standing for \~5min.

• Posture Test Heart Rate14 days

  Standing up after a period of lying down is a large physiological challenge requiring sympathetic activation to maintain perfusion pressure to the brain and void syncope. Participants will be fitted with a 2 lead EKG, a finger cuff for non-invasive BP recordings on a beat-by-beat basis and a sphygmomanometer cuff on the other arm for manual assessment of BP \[for cross calibration and safety check\]. The finger cuffs will be placed on the non-dominant hand and held in place by an arm sling so that the BP cuffs will be at heart level. HR will be assessed while participants stand up from a semi-recumbent posture and remain standing for \~5min.

• External Temperature Assessment14 days

  Skin temperatures (in degrees Celsius) will be continuously assessed using wireless Thermochron iButtons. These iButtons are small (1.6 cm x 0.6 cm), independent temperature sensors and use data loggers enclosed in a watertight stainless-steel package. The iButtons will be taped to the skin with thin, air-permeable adhesive surgical tape in up to 9 different locations and programmed prior to placement via a USB computer interface. Data will be recorded every minute. "Proximal skin temperature" is the averaged skin temperatures of infraclavicular region (mean of left and right) and sternum; "distal skin temperature" is the average skin temperatures of the wrists and ankles.

• Internal Temperature Assessment14 days

  Temperature data (in degrees Celsius) will also be collected every minute through either rectal thermistors or telemetry pill.The phase of the body temperature rhythm will be determined by the weighted average of the fitted minima of core body temperature data obtained from a single and dual-harmonic fit.

• Total Energy Expenditure14 days

  Total energy expenditure (TEE) will also be collected across the chronic sleep and circadian disruption protocol by using doubly-labeled water (DLW). DLW is a method based on administration of an oral loading dose of water labeled with both deuterium and oxygen isotope. The tracers quickly equilibrate in the total body water. Deuterium is eliminated from the body in urine only, but the oxygen isotope is eliminated in both urine and carbon dioxide; the difference of the elimination curves is equal to the amount of carbon dioxide expired over the testing period. Urine samples are collected at baseline before the loading dose and again 4-6h after consuming the water on day 1; final urine samples 14 days later.

• Changes in Alertness14 days

  The investigators will quantify a measure of alertness and hunger to determine the dynamics of acute circadian misalignment and re-entrainment on multiple aspects of waking performance. Alertness will be measured for subjective assessments via a Visual Analog Scale (VAS). The VAS Alert will be performed during sleep inertia testing, which will be the impairment observed immediately upon waking. Sleep inertia testing will occur at \~1, 10, 20, 30, 40, 50, 60, 70, 80, and 90 minutes after waking.

• Measuring Mood with POMS14 days

  Investigators will measure mood to determine the dynamics of acute circadian misalignment and re-entrainment of waking performance. Mood will be measured by utilizing the POMS questionnaire. The POMS questionnaire is a standard validated psychological test that assesses vigor, fatigue, confusion, anger-hostility, depression, and tension-anxiety by presenting 30 words to participants and requires them to rate how they identify with each word using a numerical value. Each number is associated with a scoring system via a Likert scale (e.g. "Not at All", "A Little", "Moderately", "Quite a Lot" or "Extremely"). These scores are analyzed by a Total Mood Disturbance (TMD) score via the numerical values provided by the participant. Lower scores indicate that a participant has a more consistent or stable mood profile. POMS will be administered beginning two hours after waking and repeated every two hours across wakefulness.

• Measuring Mood with PANAS14 days

  Mood will be additionally investigated by administering the PANAS questionnaire, which is a self-reported measure and consists of different words that describe emotions. There are two scales to this questionnaire, one which measures a positive affect (the ability for a participant to experience positive emotions or interact positively with others), and a negative affect (experiencing negative emotions or interacting negatively with others). Participants will be presented with a questionnaire with 20 words related to emotions and a 5-point Likert scale. Positive affect scores can range from 10-50, with higher scores representing a higher level of positive affect. Negative affect scores can also range from 10-50, and lower scores represent lower levels of negative affect. PANAS will be administered beginning two hours after waking and repeated every two hours across wakefulness.

• Changes in Degrees of Sleepiness14 days

  Investigators will use the Stanford Sleepiness Scale (SSS) for a subjective assessment of sleepiness. The SSS uses a 7-point Likert scale in order to quantify sleepiness at the time of test administration. Values are assigned as follows: 1. "Feeling active and vital, alert, or wide awake." 2. "Functioning at a high level, but not at peak; able to concentrate." 3. "Awake, but relaxed; responsive but not fully alert." 4. "Somewhat foggy, let down." 5. "Foggy; losing interest in remaining awake; slowed down." 6. "Sleepy, woozy, fighting sleep; prefer to lie down." 7. "No longer fighting sleep, sleep onset soon; having dream-like thoughts."

• Changes in Sustained Attention and Reaction Time14 days

  Investigators will administer the Psychomotor Vigilance Task (PVT) is a 10 minute, computer-based test in which the participant presses a button as soon as a light appears on the computer screen. This light will appear randomly every few seconds. The main measurements of this task include the mean and median reaction time in milliseconds and sustained attention, as well as false responses. False responses refers to a participant pressing the button before a light is displayed on the computer screen. Individuals who are sleep deprived or are sleep deficit tend to display decreased alertness, declined psychomotor skills, and increased false responses, and therefore have a slower overall reaction time. This test will be administered starting two hours after waking and repeated every two hours across wakefulness.

• Changes in Cognitive Performance14 days

  Cognitive performance will be measured by investigators administering the Digit Symbol Substitution Test (DSST). This is a computer test that presents participants with abstract symbols associated with numbers on a computer screen. The participant must match the symbol that appears on the screen with the corresponding abstract symbol and number. The DSST is a 90 second test and results measured include the total correct and participant errors. Higher scores with fewer errors indicate increased cognitive performance. The DSST will be performed during sleep inertia testing, which will be the impairment observed immediately upon waking. Sleep inertia testing will occur at \~1, 10, 20, 30, 40, 50, 60, 70, 80, and 90 minutes after waking.

• Changes in Working Memory14 days

  The addition (ADD) task is a 2-digit addition task that will be administered via computer test every 2h to assess working memory. Participants are required to answer as many addition questions as they can within a certain time frame. Results measured include the total correct and participant errors. Higher scores with fewer errors indicate an increased ability to hold information temporarily. The ADD task will be administered two hours after waking and repeated every two hours across wakefulness.