Using speckle correlations for single-shot 3D imaging.

Recovery of a 3D object behind a scattering medium is an important problem in many fields, including biomedical and defense applications. Speckle correlation imaging can recover objects in a single shot but contains no depth information. To date, its extension to 3D recovery has relied on multiple measurements, multi-spectral light, or pre-calibration of the speckle with a reference object. Here, we show that the presence of a point source behind the scatterer enables single-shot reconstruction of multiple objects at multiple depths. The method relies on speckle scaling from the axial memory effect, in addition to the transverse one, and recovers objects directly, without the need for phase retrieval. We provide simulation and experimental results to show object reconstructions at different depths with a single-shot measurement. We also provide theoretical principles describing the region where speckle scales with axial distance and its effects on the depth of field. Our technique will be useful where a natural point source exists, such as fluorescence imaging or car headlights in fog.

Daytime light exposure is a strong predictor of seasonal variation in sleep and circadian timing of university students.

In the absence of electric light, sleep for humans typically starts soon after dusk and at higher latitudes daily sleep timing changes seasonally as photoperiod changes. However, access to electric light shields humans from natural photoperiod changes, and whether seasonal changes in sleep occur despite this isolation from the natural light-dark cycle remains a matter of controversy. We measured sleep timing in over 500 university students living in the city of Seattle, WA (47.6°N) throughout the four seasons; we show that even when students are following a school schedule, sleep timing is delayed during the fall and winter. For instance, during the winter school days, students fell asleep 35 min later and woke up 27 min later (under daylight-savings time) than students during the summer school days, a change that is an hour larger relative to solar midnight. Furthermore, chronotype defined by mid-sleep on free days corrected for oversleep (MSFc), an indirect estimate of circadian phase, was more than 30 min later in the winter compared with the summer. Analysis of the effect of light exposure showed that the number of hours of light exposure to at least 50 lux during the daytime was a stronger predictor of MSFc than the exposure time to this illuminance after dusk. Specifically, MSFc was advanced by 30 min for each additional hour of light exposure during daytime and delayed by only 15 min for each additional hour of postdusk exposure to light. Additionally, the time of the day of exposure to high light intensities was more predictive of MSFc when daytime exposure was considered than when exposure for the full 24-h day was considered. Our results show that although sleep time is highly synchronized to social time, a delayed timing of sleep is evident during the winter months. They also suggest that daily exposure to daylight is key to prevent this delayed phase of the circadian clock and thus circadian disruption that is typically exacerbated in high-latitude winters.

Feasibility of time-restricted eating and impacts on cardiometabolic health in 24-h shift workers: The Healthy Heroes randomized control trial.

Over a quarter of the workforce in industrialized countries does shift work, which increases the risk for cardiometabolic disease. Yet shift workers are often excluded from lifestyle intervention studies to reduce this risk. In a randomized control trial with 137 firefighters who work 24-h shifts (23-59 years old, 9% female), 12 weeks of 10-h time-restricted eating (TRE) was feasible, with TRE participants decreasing their eating window (baseline, mean 14.13 h, 95% CI 13.78-14.47 h; intervention, 11.13 h, 95% CI 10.73-11.54 h, p = 3.29E-17) with no adverse effects, and improved quality of life assessed via SF-36 (ClinicalTrials.gov: NCT03533023). Compared to the standard of care (SOC) arm, TRE significantly decreased VLDL particle size. In participants with elevated cardiometabolic risks at baseline, there were significant reductions in TRE compared to SOC in glycated hemoglobin A1C and diastolic blood pressure. For individuals working a 24-h shift schedule, TRE is feasible and can improve cardiometabolic health, especially for individuals with increased risk. VIDEO ABSTRACT.

Pixel super-resolution with spatially entangled photons.

Pixelation occurs in many imaging systems and limits the spatial resolution of the acquired images. This effect is notably present in quantum imaging experiments with correlated photons in which the number of pixels used to detect coincidences is often limited by the sensor technology or the acquisition speed. Here, we introduce a pixel super-resolution technique based on measuring the full spatially-resolved joint probability distribution (JPD) of spatially-entangled photons. Without shifting optical elements or using prior information, our technique increases the pixel resolution of the imaging system by a factor two and enables retrieval of spatial information lost due to undersampling. We demonstrate its use in various quantum imaging protocols using photon pairs, including quantum illumination, entanglement-enabled quantum holography, and in a full-field version of N00N-state quantum holography. The JPD pixel super-resolution technique can benefit any full-field imaging system limited by the sensor spatial resolution, including all already established and future photon-correlation-based quantum imaging schemes, bringing these techniques closer to real-world applications.

Associations between the timing of eating and weight-loss in calorically restricted healthy adults: Findings from the CALERIE study.

Calorie restriction (CR) and time-restricted eating (TRE) are distinctly different dietary management strategies with overlapping health outcomes. After two years of CR, healthy participants in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) study showed significant weight-loss relative to the ad libitum intake control group and achieved 12% CR on average. Preclinical rodent studies have shown that sustaining a consistent eating interval of 8-12 h between the first and last calories of each day-without reducing daily calorie intake-can impart health benefits that partly overlap with those imparted by CR. Preclinical CR protocols often inadvertently restrict eating interval, and conversely, clinical studies of TRE often inadvertently result in modest CR. Other factors related to daily timing of food intake, such as breakfast skipping, and early food intake also impact health outcomes. These observations have raised the possibility that CR protocols can be further optimized by adopting relevant aspects of eating patterns to boost weight loss and health outcomes. With a goal to inform CR protocols that aim to optimize eating patterns, the objective of this secondary analysis was to test aspects of daily timing of food intake associated with greater weight loss in the CALERIE study participants. We found no difference in the daily time window of energy intake between the CR and control arms. In the CALERIE trial, weight change was used as a proxy for adherence to CR, and hence we used linear models to test the relationships among CR, weight loss, and temporal aspects of daily eating pattern. We found that CR alone could explain 41% of the variance in weight loss. We tested the contribution of eating interval, time to 50% daily calorie intake, and day-to-day shifts in the time of the first (breakfast) or last meal consumed. We found that eating interval and variation in the timing of the first and last meals significantly influenced weight loss after controlling for CR. Our models suggest that shorter eating intervals are associated with greater CR (1% of the variance explained) and facilitate additional weight loss. Our models suggest that less day to day variation in first mealtime is directly associated with weight loss (6% of the variance explained). More regular first meal timing is also associated with greater CR (2% of the variance explained). Likewise, regular timing of the last daily meal is directly associated with weight loss (1% of the variance explained) and greater CR (1% of the variance explained). The time to 50% of daily calorie intake or consuming half the caloric intake earlier in the day is associated with additional CR (2% of the variance explained). In summary, these secondary analyses on CALERIE data suggest that - in order to maximize CR and weight loss - future CR protocols should encourage participants to adopt consistent timing of their first and last meals, a shorter eating window, and earlier consumption of food.

Ultrahigh-Resolution, Label-Free Hyperlens Imaging in the Mid-IR.

The hyperbolic phonon polaritons supported in hexagonal boron nitride (hBN) with long scattering lifetimes are advantageous for applications such as super-resolution imaging via hyperlensing. Yet, hyperlens imaging is challenging for distinguishing individual and closely spaced objects and for correlating the complicated hyperlens fields with the structure of an unknown object underneath. Here, we make significant strides to overcome each of these challenges. First, we demonstrate that monoisotopic h11BN provides significant improvements in spatial resolution, experimentally resolving structures as small as 44 nm and those with sub 25 nm spacings at 6.76 µm free-space wavelength. We also present an image reconstruction algorithm that provides a structurally accurate, visual representation of the embedded objects from the complex hyperlens field. Further, we offer additional insights into optimizing hyperlens performance on the basis of material properties, with an eye toward realizing far-field imaging modalities. Thus, our results significantly advance label-free, high-resolution, spectrally selective hyperlens imaging and image reconstruction methodologies.

Protocol for a randomised controlled trial on the feasibility and effects of 10-hour time-restricted eating on cardiometabolic disease risk among career firefighters doing 24-hour shift work: the Healthy Heroes Study.

INTRODUCTION: Career firefighters experience chronic circadian rhythm disruption, increasing their risk of cardiometabolic disease. The recent discovery that eating patterns regulate circadian rhythmicity in metabolic organs has raised the hypothesis that maintaining a consistent daily cycle of eating and fasting can support circadian rhythms and reduce disease risks. Preclinical animal studies and preliminary clinical trials have shown promising effects of time-restricted eating (TRE) to reduce disease risk without compromising physical performance. However, there is a lack of research on TRE in shift workers including firefighters. This study aims to investigate the feasibility and efficacy of 10-hour TRE on health parameters that contribute to cardiometabolic disease risks among career firefighters who work on a 24-hour shift schedule. METHODS AND ANALYSES: The Healthy Heroes Study is a randomised controlled parallel open-label clinical trial with 150 firefighters over 1 year. Firefighters are randomised with a 1:1 ratio to either the control or intervention group. The control group receives Mediterranean diet nutritional counselling (standard of care, 'SOC'). The intervention group receives the same SOC and a self-selected 10-hour TRE window. After the 2-week baseline, participants enter a 3-month monitored intervention, followed by a 9-month self-guided period with follow-up assessments. The impact of TRE on blood glucose, body weight, body composition, biomarkers (neuroendocrine, inflammatory and metabolic), sleep and mood is evaluated. These assessments occur at baseline, at the end of intervention and at 6, 9 and 12-month follow-ups. Temporal calorie intake is monitored with the smartphone application myCircadianClock throughout the study. Continuous glucose monitors, wrist-worn actigraphy device and questionnaires are used to monitor glucose levels, activity, sleep and light exposure. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Boards of the University of California San Diego and the Salk Institute for Biological Studies. Results will be disseminated through peer-reviewed manuscripts, reports and presentations. TRIAL REGISTRATION NUMBER: NCT03533023; Pre result.

Time-Restricted Eating Effects on Body Composition and Metabolic Measures in Humans who are Overweight: A Feasibility Study.

OBJECTIVE: In contrast to intentionally restricting energy intake, restricting the eating window may be an option for treating obesity. By comparing time-restricted eating (TRE) with an unrestricted (non-TRE) control, it was hypothesized that TRE facilitates weight loss, alters body composition, and improves metabolic measures. METHODS: Participants (17 women and 3 men; mean [SD]: 45.5 [12.1] years; BMI 34.1 [7.5] kg/m2 ) with a prolonged eating window (15.4 [0.9] hours) were randomized to TRE (n = 11: 8-hour window, unrestricted eating within window) versus non-TRE (n = 9: unrestricted eating) for 12 weeks. Weight, body composition (dual x-ray absorptiometry), lipids, blood pressure, 2-hour oral glucose tolerance, 2-week continuous glucose monitoring, and 2-week physical activity (actigraphy assessed) were measured during the pre- and end-intervention periods. RESULTS: The TRE group significantly reduced the eating window (end-intervention window: 9.9 [2.0] hours) compared with the non-TRE group (end-intervention window: 15.1 [1.1] hours) (P < 0.01). Compared with non-TRE, TRE decreased the number of eating occasions, weight, lean mass, and visceral fat (all P ≤ 0.05). Compared with preintervention measures, the TRE group reduced the number of eating occasions (-21.9% [30.1%]) and reduced weight (-3.7% [1.8%]), fat mass (-4% [2.9%]), lean mass (-3.0% [2.7%]), and visceral fat (-11.1% [13.4%]) (all P ≤ 0.05). Physical activity and metabolic measures remained unchanged. CONCLUSIONS: In the setting of a randomized trial, TRE presents a simplified view of food intake that reduces weight.

Ten-Hour Time-Restricted Eating Reduces Weight, Blood Pressure, and Atherogenic Lipids in Patients with Metabolic Syndrome.

In animal models, time-restricted feeding (TRF) can prevent and reverse aspects of metabolic diseases. Time-restricted eating (TRE) in human pilot studies reduces the risks of metabolic diseases in otherwise healthy individuals. However, patients with diagnosed metabolic syndrome often undergo pharmacotherapy, and it has never been tested whether TRE can act synergistically with pharmacotherapy in animal models or humans. In a single-arm, paired-sample trial, 19 participants with metabolic syndrome and a baseline mean daily eating window of ≥14 h, the majority of whom were on a statin and/or antihypertensive therapy, underwent 10 h of TRE (all dietary intake within a consistent self-selected 10 h window) for 12 weeks. We found this TRE intervention improves cardiometabolic health for patients with metabolic syndrome receiving standard medical care including high rates of statin and anti-hypertensive use. TRE is a potentially powerful lifestyle intervention that can be added to standard medical practice to treat metabolic syndrome. VIDEO ABSTRACT.

Quantum image distillation.

Imaging with quantum states of light promises advantages over classical approaches in terms of resolution, signal-to-noise ratio, and sensitivity. However, quantum detectors are particularly sensitive sources of classical noise that can reduce or cancel any quantum advantage in the final result. Without operating in the single-photon counting regime, we experimentally demonstrate distillation of a quantum image from measured data composed of a superposition of both quantum and classical light. We measure the image of an object formed under quantum illumination (correlated photons) that is mixed with another image produced by classical light (uncorrelated photons) with the same spectrum and polarization, and we demonstrate near-perfect separation of the two superimposed images by intensity correlation measurements. This work provides a method to mix and distinguish information carried by quantum and classical light, which may be useful for quantum imaging, communications, and security.

Time-Restricted Feeding Improves Glucose Tolerance in Men at Risk for Type 2 Diabetes: A Randomized Crossover Trial.

OBJECTIVE: This study aimed to assess the effects of 9-hour time-restricted feeding (TRF), early (TRFe) or delayed (TRFd), on glucose tolerance in men at risk for type 2 diabetes. METHODS: Fifteen men (age 55 ± 3 years, BMI 33.9 ± 0.8 kg/m2 ) wore a continuous glucose monitor for 7 days of baseline assessment and during two 7-day TRF conditions. Participants were randomized to TRFe (8 am to 5 pm) or TRFd (12 pm to 9 pm), separated by a 2-week washout phase. Glucose, insulin, triglycerides, nonesterified fatty acids, and gastrointestinal hormone incremental areas under the curve were calculated following a standard meal on days 0 and 7 at 8 am (TRFe) or 12 pm (TRFd). RESULTS: TRF improved glucose tolerance as assessed by a reduction in glucose incremental area under the curve (P = 0.001) and fasting triglycerides (P = 0.003) on day 7 versus day 0. However, there were no mealtime by TRF interactions in any of the variables examined. There was also no effect of TRF on fasting and postprandial insulin, nonesterified fatty acids, or gastrointestinal hormones. Mean fasting glucose by continuous glucose monitor was lower in TRFe (P = 0.02) but not TRFd (P = 0.17) versus baseline, but there was no difference between TRF conditions. CONCLUSIONS: While only TRFe lowered mean fasting glucose, TRF improved glycemic responses to a test meal in men at risk for type 2 diabetes regardless of the clock time that TRF was initiated.

High-resolution light-field imaging via phase space retrieval.

By combining a high-resolution image from a standard camera with a low-resolution light-field image from a lenslet array, we numerically reconstruct a high-resolution light-field image. We experimentally demonstrate the method by creating a high-definition 3D image of a human cheek cell with a commercially available microscope.

Nonlinear Imaging using Object-Dependent Illumination.

Nonlinear imaging systems can surpass the limits of linear optics, but nearly all rely on physical media and atomic/molecular response to work. These materials are constrained by their physical properties, such as frequency selectivity, environmental sensitivity, time behavior, and fixed nonlinear response. Here, we show that electro-optic spatial light modulators (SLMs) can take the place of traditional nonlinear media, provided that there is a feedback between the shape of the object and the pattern on the modulator. This feedback creates a designer illumination that generalizes the field of adaptive optics to include object-dependent patterns. Unlike physical media, the SLM response can provide a wide range of mathematical functions, operate over broad bandwidths at high speeds, and work equally well at high power and single-photon levels. We demonstrate the method experimentally for both coherent and incoherent light.

Adaptive Quantum Optics with Spatially Entangled Photon Pairs.

Light shaping facilitates the preparation and detection of optical states and underlies many applications in communications, computing, and imaging. In this Letter, we generalize light shaping to the quantum domain. We show that patterns of phase modulation for classical laser light can also shape higher orders of spatial coherence, allowing deterministic tailoring of high-dimensional quantum entanglement. By modulating spatially entangled photon pairs, we create periodic, topological, and random patterns of quantum illumination, without effect on intensity. We then structure the quantum illumination to simultaneously compensate for entanglement that has been randomized by a scattering medium and to characterize the medium's properties via a quantum measurement of the optical memory effect. The results demonstrate fundamental aspects of spatial coherence and open the field of adaptive quantum optics.

Predicting age from the transcriptome of human dermal fibroblasts.

Biomarkers of aging can be used to assess the health of individuals and to study aging and age-related diseases. We generate a large dataset of genome-wide RNA-seq profiles of human dermal fibroblasts from 133 people aged 1 to 94 years old to test whether signatures of aging are encoded within the transcriptome. We develop an ensemble machine learning method that predicts age to a median error of 4 years, outperforming previous methods used to predict age. The ensemble was further validated by testing it on ten progeria patients, and our method is the only one that predicts accelerated aging in these patients.

Sleepmore in Seattle: Later school start times are associated with more sleep and better performance in high school students.

Most teenagers are chronically sleep deprived. One strategy proposed to lengthen adolescent sleep is to delay secondary school start times. This would allow students to wake up later without shifting their bedtime, which is biologically determined by the circadian clock, resulting in a net increase in sleep. So far, there is no objective quantitative data showing that a single intervention such as delaying the school start time significantly increases daily sleep. The Seattle School District delayed the secondary school start time by nearly an hour. We carried out a pre-/post-research study and show that there was an increase in the daily median sleep duration of 34 min, associated with a 4.5% increase in the median grades of the students and an improvement in attendance.

General Model of Photon-Pair Detection with an Image Sensor.

We develop an analytic model that relates intensity correlation measurements performed by an image sensor to the properties of photon pairs illuminating it. Experiments using an effective single-photon counting camera, a linear electron-multiplying charge-coupled device camera, and a standard CCD camera confirm the model. The results open the field of quantum optical sensing using conventional detectors.

Massively Parallel Coincidence Counting of High-Dimensional Entangled States.

Entangled states of light are essential for quantum technologies and fundamental tests of physics. Current systems rely on entanglement in 2D degrees of freedom, e.g., polarization states. Increasing the dimensionality provides exponential speed-up of quantum computation, enhances the channel capacity and security of quantum communication protocols, and enables quantum imaging; unfortunately, characterizing high-dimensional entanglement of even bipartite quantum states remains prohibitively time-consuming. Here, we develop and experimentally demonstrate a new theory of camera detection that leverages the massive parallelization inherent in an array of pixels. We show that a megapixel array, for example, can measure a joint Hilbert space of 1012 dimensions, with a speed-up of nearly four orders-of-magnitude over traditional methods. The technique uses standard geometry with existing technology, thus removing barriers of entry to quantum imaging experiments, generalizes readily to arbitrary numbers of entangled photons, and opens previously inaccessible regimes of high-dimensional quantum optics.

Enhanced phase retrieval using nonlinear dynamics.

Historically, phase retrieval algorithms have relied on linear propagation between two different amplitude (intensity) measurements. While generally successful, these algorithms have many issues, including susceptibility to noise, local minima, and indeterminate initial and final conditions. Here, we show that nonlinear propagation overcomes these issues, as intensity-induced changes to the index of refraction create additional constraints on the phase. More specifically, phase-matching conditions (conservation of wave energy and momentum) induce an object-dependent resonance between the measured amplitudes and the unknown phase. The result is a non-classical convergence profile in the reconstruction algorithm that contains a zero crossing, where the observable minimum in amplitude error and the unobservable minimum in phase error align at the same iteration number. We demonstrate this convergence experimentally in a photorefractive crystal, showing that there is a clear rule for stopping iterations. We find that the optimum phase retrieval occurs for a nonlinear strength that gives minimal correlation between the linear and nonlinear output amplitudes, i.e. a condition that maximizes the information diversity between linear and nonlinear propagation. The corresponding algorithm greatly improves the conventional Gerchberg-Saxton result and holds much potential for enhancing other methods of diffractive imaging.

Imagery May Arise from Associations Formed through Sensory Experience: A Network of Spiking Neurons Controlling a Robot Learns Visual Sequences in Order to Perform a Mental Rotation Task.

Mental imagery occurs "when a representation of the type created during the initial phases of perception is present but the stimulus is not actually being perceived." How does the capability to perform mental imagery arise? Extending the idea that imagery arises from learned associations, we propose that mental rotation, a specific form of imagery, could arise through the mechanism of sequence learning-that is, by learning to regenerate the sequence of mental images perceived while passively observing a rotating object. To demonstrate the feasibility of this proposal, we constructed a simulated nervous system and embedded it within a behaving humanoid robot. By observing a rotating object, the system learns the sequence of neural activity patterns generated by the visual system in response to the object. After learning, it can internally regenerate a similar sequence of neural activations upon briefly viewing the static object. This system learns to perform a mental rotation task in which the subject must determine whether two objects are identical despite differences in orientation. As with human subjects, the time taken to respond is proportional to the angular difference between the two stimuli. Moreover, as reported in humans, the system fills in intermediate angles during the task, and this putative mental rotation activates the same pathways that are activated when the system views physical rotation. This work supports the proposal that mental rotation arises through sequence learning and the idea that mental imagery aids perception through learned associations, and suggests testable predictions for biological experiments.