Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder.

Patterns of daily human activity are controlled by an intrinsic circadian clock that promotes ∼24 hr rhythms in many behavioral and physiological processes. This system is altered in delayed sleep phase disorder (DSPD), a common form of insomnia in which sleep episodes are shifted to later times misaligned with the societal norm. Here, we report a hereditary form of DSPD associated with a dominant coding variation in the core circadian clock gene CRY1, which creates a transcriptional inhibitor with enhanced affinity for circadian activator proteins Clock and Bmal1.

Concentration-Response Modeling of ECG Data From Early-Phase Clinical Studies as an Alternative Clinical and Regulatory Approach to Assessing QT Risk - Experience From the Development Program of Lemborexant.

Lemborexant is a novel dual orexin receptor antagonist being developed to treat insomnia. Its potential to cause QT prolongation was evaluated using plasma concentration-response (CR) modeling applied to data from 2 multiple ascending-dose (MAD) studies. In the primary MAD study, placebo or lemborexant (2.

Alterations in skin temperature and sleep in the fear of harm phenotype of pediatric bipolar disorder.

In children diagnosed with pediatric bipolar disorder (PBD), disturbances in the quality of sleep and wakefulness are prominent. A novel phenotype of PBD called Fear of Harm (FOH) associated with separation anxiety and aggressive obsessions is associated with sleep onset insomnia, parasomnias (nightmares, night-terrors, enuresis), REM sleep-related problems, and morning sleep inertia. Children with FOH often experience thermal discomfort (e.

Effects of a month-long napping regimen in older individuals.

Objectives: To examine the effects of a month-long nap regimen using one of two durations (45 minutes or 2 hours) on nighttime sleep and waking function in a group of healthy older participants and to assess the degree to which healthy older individuals are willing and able to adhere to such napping regimens.

Design: Three laboratory sessions, with 2-week at-home recording interspersed, using a between-participants approach.

Setting: Laboratory of Human Chronobiology at Weill Cornell Medical College and participants' homes.

Measuring melatonin in humans.

Study Objectives: To provide guidelines for collecting and analyzing urinary, salivary, and plasma melatonin, thereby assisting clinicians and researchers in determining which method of measuring melatonin is most appropriate for their particular needs and facilitating the comparison of data between laboratories.

Methods: A modified RAND process was utilized to derive recommendations for methods of measuring melatonin in humans.

Results: Consensus-based guidelines are presented for collecting and analyzing melatonin for studies that are conducted in the natural living environment, the clinical setting, and in-patient research facilities under controlled conditions.

Sex hormones, sleep, and core body temperature in older postmenopausal women.

Study Objectives: Assessment of relationships between polysomnographic sleep, sex hormones, and core body temperature in postmenopausal women.

Design And Participants: Ten women aged 57 to 71 years, at least 5 years past menopause.

Setting: Laboratory of Human Chronobiology at Weill Cornell Medical College.

Delayed sleep phase disorder in temporal isolation.

Study Objectives: This study sought to characterize sleep and the circadian rhythm of body core temperature of an individual with delayed sleep phase disorder (DSPD) in the absence of temporal cues and social entrainment and to compare those measures to age-matched normal control subjects studied under identical conditions.

Design: Polysomnography and body temperature were recorded continuously for 4 days in entrained conditions, followed immediately by 17 days in a "free-running" environment.

Setting: Temporal isolation facility in the Laboratory of Human Chronobiology, Weill Cornell Medical College.

Vagus nerve stimulation in children with mitochondrial electron transport chain deficiencies.

We retrospectively investigated outcome data for vagus nerve stimulation (VNS) in children less than 12 years of age with intractable seizures and mitochondrial disease. Five children with a mitochondrial disease, due to electron transport chain deficiency, were studied. Information was collected from clinic visits prior to, and subsequent to, VNS implantation.

The nature of spontaneous sleep across adulthood.

The decline in sleep quality that often accompanies aging is thought to be the consequence of alterations in both circadian and homeostatic processes widely assumed to be responsible for sleep/wake regulation. A number of experimental approaches have been used to examine various aspects of age-related sleep changes, but none has examined spontaneous sleep across the entire 24-h day. Using the 'disentrainment' protocol, we studied such sleep in young, middle-aged and older adults.

Vagus nerve stimulation for intractable seizures in children.

Forty-three children less than 12 years of age having intractable seizures were treated with vagus nerve stimulation. Five children were monitored for <12 months, 16 children for 12 to 17 months, and 22 children for > or =18 months with overall median seizure reduction of 55%. Thirty-seven percent had at least 90% reduction.

Effects of a nap on nighttime sleep and waking function in older subjects.

Objectives: To examine, in older subjects, the effect on waking function of increasing 24-hour sleep amounts by providing a nap opportunity; to assess what effects an afternoon nap may have on subsequent nighttime sleep quality and composition.

Design: Two-session, within-subject laboratory design.

Setting: The study was conducted in the Laboratory of Human Chronobiology at Weill Cornell Medical College.

Technology transfer concerns of college graduates with disabilities: Profiles in transition from higher education to competitive careers.

The article describes the technology transfer concerns reported by a small sample (N=14) of recent college graduates with disabilities. In structured, in-depth interviews, researchers asked respondents to reflect on the extent to which they had utilized technology resources during their college years in preparation for the world of work. Results suggest that colleges and universities need to play a more active role in introducing students with disabilities to both generalized and assistive technology services.

Failure of timed bright light exposure to alleviate age-related sleep maintenance insomnia.

Objectives: To determine whether a twice-weekly maintenance schedule of evening bright light exposure is effective in alleviating sleep maintenance insomnia on a long-term basis, after the establishment of a more favorable phase relationship between the core body temperature (CBT) rhythm and sleep.

Design: Subjects underwent light treatment while living at home. Eleven to 13 consecutive days of acute light treatment (active) were followed by a 3-month maintenance light treatment period (active or control).