SleepNet: Attention-Enhanced Robust Sleep Prediction using Dynamic Social Networks

Sleep behavior significantly impacts health and acts as an indicator of physical and mental well-being. Monitoring and predicting sleep behavior with ubiquitous sensors may therefore assist in both sleep management and tracking of related health conditions. While sleep behavior depends on, and is reflected in the physiology of a person, it is also impacted by external factors such as digital media usage, social network contagion, and the surrounding weather. In this work, we propose SleepNet, a system that exploits social contagion in sleep behavior through graph networks and integrates it with physiological and phone data extracted from ubiquitous mobile and wearable devices for predicting next-day sleep labels about sleep duration. Our architecture overcomes the limitations of large-scale graphs containing connections irrelevant to sleep behavior by devising an attention mechanism. The extensive experimental evaluation highlights the improvement provided by incorporating social networks in the model. Additionally, we conduct robustness analysis to demonstrate the system's performance in real-life conditions. The outcomes affirm the stability of SleepNet against perturbations in input data. Further analyses emphasize the significance of network topology in prediction performance revealing that users with higher eigenvalue centrality are more vulnerable to data perturbations.Comment: Accepted for publication in Proceedings of the ACM on Interactive, Mobile, Wearable and Ubiquitous Technologies (IMWUT), 8 (March 2024

A Physiologically Based Model of Orexinergic Stabilization of Sleep and Wake

The orexinergic neurons of the lateral hypothalamus (Orx) are essential for regulating sleep-wake dynamics, and their loss causes narcolepsy, a disorder characterized by severe instability of sleep and wake states. However, the mechanisms through which Orx stabilize sleep and wake are not well understood. In this work, an explanation of the stabilizing effects of Orx is presented using a quantitative model of important physiological connections between Orx and the sleep-wake switch. In addition to Orx and the sleep-wake switch, which is composed of mutually inhibitory wake-active monoaminergic neurons in brainstem and hypothalamus (MA) and the sleep-active ventrolateral preoptic neurons of the hypothalamus (VLPO), the model also includes the circadian and homeostatic sleep drives. It is shown that Orx stabilizes prolonged waking episodes via its excitatory input to MA and by relaying a circadian input to MA, thus sustaining MA firing activity during the circadian day. During sleep, both Orx and MA are inhibited by the VLPO, and the subsequent reduction in Orx input to the MA indirectly stabilizes sustained sleep episodes. Simulating a loss of Orx, the model produces dynamics resembling narcolepsy, including frequent transitions between states, reduced waking arousal levels, and a normal daily amount of total sleep. The model predicts a change in sleep timing with differences in orexin levels, with higher orexin levels delaying the normal sleep episode, suggesting that individual differences in Orx signaling may contribute to chronotype. Dynamics resembling sleep inertia also emerge from the model as a gradual sleep-to-wake transition on a timescale that varies with that of Orx dynamics. The quantitative, physiologically based model developed in this work thus provides a new explanation of how Orx stabilizes prolonged episodes of sleep and wake, and makes a range of experimentally testable predictions, including a role for Orx in chronotype and sleep inertia

Evolution of the Near-Infrared Tully-Fisher Relation: Constraints on the Relationship Between the Stellar and Total Masses of Disk Galaxies since z=1

Using a combination of Keck spectroscopy and near-infrared imaging, we investigate the K-band and stellar mass Tully-Fisher relation for 101 disk galaxies at 0.2 < z < 1.2, with the goal of placing the first observational constraints on the assembly history of halo and stellar mass. Our main result is a lack of evolution in either the K-band or stellar mass Tully-Fisher relation from z = 0 - 1.2. Furthermore, although our sample is not statistically complete, we consider it suitable for an initial investigation of how the fraction of total mass that has condensed into stars is distributed with both redshift and total halo mass. We calculate stellar masses from optical and near-infrared photometry and total masses from maximum rotational velocities and disk scale lengths, utilizing a range of model relationships derived analytically and from simulations. We find that the stellar/total mass distribution and stellar-mass Tully-Fisher relation for z > 0.7 disks is similar to that at lower redshift, suggesting that baryonic mass is accreted by disks along with dark matter at z < 1, and that disk galaxy formation at z < 1 is hierarchical in nature. We briefly discuss the evolutionary trends expected in conventional structure formation models and the implications of extending such a study to much larger samples.Comment: ApJ, in press, 9 page

Power Analysis for Human Melatonin Suppression Experiments

In humans, the nocturnal secretion of melatonin by the pineal gland is suppressed by ocular exposure to light. In the laboratory, melatonin suppression is a biomarker for this neuroendocrine pathway. Recent work has found that individuals differ substantially in their melatonin-suppressive response to light, with the most sensitive individuals being up to 60 times more sensitive than the least sensitive individuals. Planning experiments with melatonin suppression as an outcome needs to incorporate these individual differences, particularly in common resource-limited scenarios where running within-subjects studies at multiple light levels is costly and resource-intensive and may not be feasible with respect to participant compliance. Here, we present a novel framework for virtual laboratory melatonin suppression experiments, incorporating a Bayesian statistical model. We provide a Shiny web app for power analyses that allows users to modify various experimental parameters (sample size, individual-level heterogeneity, statistical significance threshold, light levels), and simulate a systematic shift in sensitivity (e.g., due to a pharmacological or other intervention). Our framework helps experimenters to design compelling and robust studies, offering novel insights into the underlying biological variability in melatonin suppression relevant for practical applications

Genome-wide gene by environment study of time spent in daylight and chronotype identifies emerging genetic architecture underlying light sensitivity

Study Objectives: Light is the primary stimulus for synchronizing the circadian clock in humans. There are very large interindividual differences in the sensitivity of the circadian clock to light. Little is currently known about the genetic basis for these interindividual differences.Methods: We performed a genome-wide gene-by-environment interaction study (GWIS) in 280 897 individuals from the UK Biobank cohort to identify genetic variants that moderate the effect of daytime light exposure on chronotype (individual time of day preference), acting as “light sensitivity” variants for the impact of daylight on the circadian system.Results: We identified a genome-wide significant SNP mapped to the ARL14EP gene (rs3847634; p &lt; 5 × 10−8), where additional minor alleles were found to enhance the morningness effect of daytime light exposure (βGxE = −.03, SE = 0.005) and were associated with increased gene ARL14EP expression in brain and retinal tissues. Gene-property analysis showed light sensitivity loci were enriched for genes in the G protein-coupled glutamate receptor signaling pathway and genes expressed in Per2+ hypothalamic neurons. Linkage disequilibrium score regression identified Bonferroni significant genetic correlations of greater light sensitivity GWIS with later chronotype and shorter sleep duration. Greater light sensitivity was nominally genetically correlated with insomnia symptoms and risk for post-traumatic stress disorder (PTSD).Conclusions: This study is the first to assess light as an important exposure in the genomics of chronotype and is a critical first step in uncovering the genetic architecture of human circadian light sensitivity and its links to sleep and mental healt

The Magnitude-Size Relation of Galaxies out to z ~ 1

As part of the Deep Extragalactic Evolutionary Probe (DEEP) survey, a sample of 190 field galaxies (I_{814} <= 23.5) in the ``Groth Survey Strip'' has been used to analyze the magnitude-size relation over the range 0.1 < z < 1.1. The survey is statistically complete to this magnitude limit. All galaxies have photometric structural parameters, including bulge fractions (B/T), from Hubble Space Telescope images, and spectroscopic redshifts from the Keck Telescope. The analysis includes a determination of the survey selection function in the magnitude-size plane as a function of redshift, which mainly drops faint galaxies at large distances. Our results suggest that selection effects play a very important role. A first analysis treats disk-dominated galaxies with B/T < 0.5. If selection effects are ignored, the mean disk surface brightness (averaged over all galaxies) increases by ~1.3 mag from z = 0.1 to 0.9. However, most of this change is plausibly due to comparing low luminosity galaxies in nearby redshift bins to high luminosity galaxies in distant bins. If this effect is allowed for, no discernible evolution remains in the disk surface brightness of bright (M_B < -19) disk-dominated galaxies. A second analysis treats all galaxies by substituting half-light radius for disk scale length, with similar conclusions. Indeed, at all redshifts, the bulk of galaxies is consistent with the magnitude-size envelope of local galaxies, i.e., with little or no evolution in surface brightness. In the two highest redshift bins (z > 0.7), a handful of luminous, high surface brightness galaxies appears that occupies a region of the magnitude-size plane rarely populated by local galaxies. Their wide range of colors and bulge fractions points to a variety of possible origins.Comment: 19 pages, 12 figures. Accepted for publication in the Astrophysical Journa

Neural responses to facial and vocal expressions of fear and disgust

Neuropsychological studies report more impaired responses to facial expressions of fear than disgust in people with amygdala lesions, and vice versa in people with Huntington's disease. Experiments using functional magnetic resonance imaging (fMRI) have confirmed the role of the amygdala in the response to fearful faces and have implicated the anterior insula in the response to facial expressions of disgust. We used fMRI to extend these studies to the perception of fear and disgust from both facial and vocal expressions. Consistent with neuropsychological findings, both types of fearful stimuli activated the amygdala. Facial expressions of disgust activated the anterior insula and the caudate-putamen; vocal expressions of disgust did not significantly activate either of these regions. All four types of stimuli activated the superior temporal gyrus. Our findings therefore (i) support the differential localization of the neural substrates of fear and disgust; (ii) confirm the involvement of the amygdala in the emotion of fear, whether evoked by facial or vocal expressions; (iii) confirm the involvement of the anterior insula and the striatum in reactions to facial expressions of disgust; and (iv) suggest a possible general role for the perception of emotional expressions for the superior temporal gyrus

Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis

Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership, U.S. Agency for International Development, U.K. Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin.Background: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization. Results: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group. Conclusions: The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.)Publisher PDFPeer reviewe

The effects of self-selected light-dark cycles and social constraints on human sleep and circadian timing: a modeling approach

Why do we go to sleep late and struggle to wake up on time? Historically, light-dark cycles were dictated by the solar day, but now humans can extend light exposure by switching on artificial lights. We use a mathematical model incorporating effects of light, circadian rhythmicity and sleep homeostasis to provide a quantitative theoretical framework to understand effects of modern patterns of light consumption on the human circadian system. The model shows that without artificial light humans wakeup at dawn. Artificial light delays circadian rhythmicity and preferred sleep timing and compromises synchronisation to the solar day when wake-times are not enforced. When wake-times are enforced by social constraints, such as work or school, artificial light induces a mismatch between sleep timing and circadian rhythmicity (‘social jet-lag’). The model implies that developmental changes in sleep homeostasis and circadian amplitude make adolescents particularly sensitive to effects of light consumption. The model predicts that ameliorating social jet-lag is more effectively achieved by reducing evening light consumption than by delaying social constraints, particularly in individuals with slow circadian clocks or when imposed wake-times occur after sunrise. These theory-informed predictions may aid design of interventions to prevent and treat circadian rhythm-sleep disorders and social jet-lag

Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation.

Methamphetamine (MA) is a highly addictive psychomotor stimulant, with life-time prevalence rates of abuse ranging from 5-10% world-wide. Yet, a paucity of research exists regarding MA addiction vulnerability/resiliency and neurobiological mediators of the transition to addiction that might occur upon repeated low-dose MA exposure, more characteristic of early drug use. As stimulant-elicited neuroplasticity within dopamine neurons innervating the nucleus accumbens (NAC) and prefrontal cortex (PFC) is theorized as central for addiction-related behavioral anomalies, we used a multi-disciplinary research approach in mice to examine the interactions between sub-toxic MA dosing, motivation for MA and mesocorticolimbic monoamines. Biochemical studies of C57BL/6J (B6) mice revealed short- (1 day), as well as longer-term (21 days), changes in extracellular dopamine, DAT and/or D2 receptors during withdrawal from 10, once daily, 2 mg/kg MA injections. Follow-up biochemical studies conducted in mice selectively bred for high vs. low MA drinking (respectively, MAHDR vs. MALDR mice), provided novel support for anomalies in mesocorticolimbic dopamine as a correlate of genetic vulnerability to high MA intake. Finally, neuropharmacological targeting of NAC dopamine in MA-treated B6 mice demonstrated a bi-directional regulation of MA-induced place-conditioning. These results extend extant literature for MA neurotoxicity by demonstrating that even subchronic exposure to relatively low MA doses are sufficient to elicit relatively long-lasting changes in mesocorticolimbic dopamine and that drug-induced or idiopathic anomalies in mesocorticolimbic dopamine may underpin vulnerability/resiliency to MA addiction