All organisms exhibit significant daily rhythms in a myriad of functions from molecular levels to the level of the whole organism. Significantly, most of these rhythms will persist under constant conditions, showing that they are driven by an internal circadian clock. In birds the circadian system is composed of several interacting sites, each of which may contain a circadian clock. These sites include the pineal organ, the suprachiasmatic nucleus (SCN) of the hypothalamus, and, in some species, the eyes. Light is the most powerful entraining stimulus for circadian rhythms and, in birds, light can affect the system via three different pathways: the eyes, the pineal, and extraretinal photoreceptors located in the deep brain. Circadian pacemakers in the pineal and in the eyes of some avian species communicate with the hypothalamic pacemakers via the rhythmic synthesis and release of the hormone melatonin. Often the hypothalamic pacemakers are unable to sustain persistent rhythmicity in constant conditions in the absence of periodic melatonin input from the pineal (or eyes). It has also been proposed that pineal pacemakers may be unable to sustain rhythmicity in constant conditions without periodic neural input from the SCN. Significant variation can occur among birds in the relative roles that the pineal, the SCN, and the eyes play within the circadian system; for example, in the house sparrow pacemakers in the pineal play the predominant role, in the pigeon circadian pacemakers in both the pineal and eyes play a significant role, and in Japanese quail ocular pacemakers play the predominant role.

Our previous studies showed that the eyes of Japanese quail contain a biological clock that drives a daily rhythm of melatonin synthesis. Furthermore, we hypothesized that these ocular clocks are pacemakers because eye removal abolishes freerunning rhythms in constant darkness (DD). If the eyes are indeed acting as pacemakers, we predicted that the two ocular pacemakers in an individual bird must remain in phase in DD and, furthermore, the two ocular pacemakers would rapidly regain coupling after being forced out of phase. These predictions were confirmed by demonstrating that 1) the ocular melatonin rhythms of the two eyes maintained phase for at least 57 days in DD and 2) after ocular pacemakers were forced out of phase by alternately patching the eyes in constant light, two components of body temperature were observed that fused into a consolidated rhythm after 5-6 days in DD, showing pacemaker recoupling. The ability to maintain phase in DD and rapidly recouple after out-of-phase entrainment demonstrates that the eyes are strongly coupled pacemakers that work in synchrony to drive circadian rhythmicity in Japanese quail.

Mild traumatic brain injuries (mTBIs) are the most common type of brain injury. Timely diagnosis of mTBI is crucial in making ‘go/no-go’ decision in order to prevent repeated injury, avoid strenuous activities which may prolong recovery, and assure capabilities of high-level performance of the subject. If undiagnosed, mTBI may lead to various short- and long-term abnormalities, which include, but are not limited to impaired cognitive function, fatigue, depression, irritability, and headaches. Existing screening and diagnostic tools to detect acute and early-stage mTBIs have insufficient sensitivity and specificity. This results in uncertainty in clinical decision-making regarding diagnosis and returning to activity or requiring further medical treatment. Therefore, it is important to identify relevant physiological biomarkers that can be integrated into a mutually complementary set and provide a combination of data modalities for improved on-site diagnostic sensitivity of mTBI. In recent years, the processing power, signal fidelity, and the number of recording channels and modalities of wearable healthcare devices have improved tremendously and generated an enormous amount of data. During the same period, there have been incredible advances in machine learning tools and data processing methodologies. These achievements are enabling clinicians and engineers to develop and implement multiparametric high-precision diagnostic tools for mTBI. In this review, we first assess clinical challenges in the diagnosis of acute mTBI, and then consider recording modalities and hardware implementation of various sensing technologies used to assess physiological biomarkers that may be related to mTBI. Finally, we discuss the state of the art in machine learning-based detection of mTBI and consider how a more diverse list of quantitative physiological biomarker features may improve current data-driven approaches in providing mTBI patients timely diagnosis and treatment.

This clinical methods comparison study describes the difference between light levels measured at the wrist (Actiwatch-L) and at the eye (Daysimeter) in a postoperative in-patient population. The mean difference between the two devices was less than 10 lux at light levels less than 5000 lux. Agreement between the devices was found to decrease as eye-level light exposure increased. Measurements at eye level of 5000 lux or more corresponded to a difference between the devices of greater than 100 lux. Agreement between the eye- and wrist-level light measurements also appears to be influenced by time of day. During the day, the measurement differences were on average 50 lux higher at eye level, whereas at night they were on average 50 lux lower. Although the wrist-level monitor was found to underestimate light exposure at higher light levels, it was well tolerated by participants in the clinical setting. In contrast, the eye-level monitor was cumbersome and uncomfortable for the patients to wear. This study provides light-exposure data on patients in real conditions in the clinical environment. The results show that wrist-level monitoring provides an adequate estimate of light exposure for in-hospital circadian studies.

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