Ocean ecosystems are undergoing accelerating disruption from human impacts such as climate change. Warming ocean temperatures drive pathogenic outbreaks, increase harmful algal blooms and cause coral stress. These can have serious consequences for marine ecosystems, human health and the aquaculture industry, representing a critical One Health issue. Monitoring key marine species offers valuable insights, but current methods are resource-intensive, low-resolution and unsuitable for frequent deployment. Here we introduce a low-cost, field-deployable CRISPR biosensing platform for detecting marine organismal DNA and RNA. Harnessing the programmability of CRISPR diagnostics for environmental biosurveillance, we demonstrate versatility across three climate-linked indicators: Vibrio spp., Pseudo-nitzschia spp. and heat-stressed corals. Portable 3D-printed processor and incubator devices enable direct processing of filter-captured samples with temperature control. Field readiness is reinforced by lyophilized reagents, lateral flow readouts, dropper-based handling and a two-step multiplexed workflow, delivering results within 1 hour without laboratory instruments. Benchmarking with authentic pathogens and environmental seawater confirmed seawater tolerance and robust detection of 108 colony-forming units per filter of Vibrio pathogens, equivalent to 102 copies per microlitre for 1 litre of filtered sample. This decentralized platform reduces barriers to routine monitoring and can provide early warnings of ecosystem disturbances, while supporting One Health initiatives in the marine space. Human impacts on marine ecosystems are increasing the likelihood of pathogenic outbreaks, harmful algal blooms and coral stress. Here the authors develop a CRISPR biomonitoring tool that can help detect key marine species that are important to public health, the aquaculture sector and marine ecosystems.

Subsensory noise stimulation targeting sensory receptors has been shown to improve balance control in healthy and impaired individuals. However, the potential for application of this technique in other contexts is still unknown. Gait control and adaptation rely heavily on the input from proprioceptive organs in the muscles and joints. Here we investigated the use of subsensory noise stimulation as a means to influence motor control by altering proprioception during locomotor adaptations to forces delivered by a robot. The forces increase step length unilaterally and trigger an adaptive response that restores the original symmetry. Healthy participants performed two adaptation experiments, one with stimulation applied to the hamstring muscles and one without. We found that participants adapted faster but to a lesser extent when undergoing stimulation. We argue that this behavior is because of the dual effect that the stimulation has on the afferents encoding position and velocity in the muscle spindles.

The COVID-19 pandemic highlights the need for diagnostics that can be rapidly adapted and deployed in a variety of settings. Several SARS-CoV-2 variants have shown worrisome effects on vaccine and treatment efficacy, but no current point-of-care (POC) testing modality allows their specific identification. We have developed miSHERLOCK, a low-cost, CRISPR-based POC diagnostic platform that takes unprocessed patient saliva; extracts, purifies, and concentrates viral RNA; performs amplification and detection reactions; and provides fluorescent visual output with only three user actions and 1 hour from sample input to answer out. miSHERLOCK achieves highly sensitive multiplexed detection of SARS-CoV-2 and mutations associated with variants B.1.1.7, B.1.351, and P.1. Our modular system enables easy exchange of assays to address diverse user needs and can be rapidly reconfigured to detect different viruses and variants of concern. An adjunctive smartphone application enables output quantification, automated interpretation, and the possibility of remote, distributed result reporting.

Integrating synthetic biology into wearables could expand opportunities for noninvasive monitoring of physiological status, disease states and exposure to pathogens or toxins. However, the operation of synthetic circuits generally requires the presence of living, engineered bacteria, which has limited their application in wearables. Here we report lightweight, flexible substrates and textiles functionalized with freeze-dried, cell-free synthetic circuits, including CRISPR-based tools, that detect metabolites, chemicals and pathogen nucleic acid signatures. The wearable devices are activated upon rehydration from aqueous exposure events and report the presence of specific molecular targets by colorimetric changes or via an optical fiber network that detects fluorescent and luminescent outputs. The detection limits for nucleic acids rival current laboratory methods such as quantitative PCR. We demonstrate the development of a face mask with a lyophilized CRISPR sensor for wearable, noninvasive detection of SARS-CoV-2 at room temperature within 90 min, requiring no user intervention other than the press of a button.

The ability to track depression severity over time using passive sensing of speech would enable frequent and inexpensive monitoring, allowing rapid assessment of treatment efficacy as well as improved long term care of individuals at high risk for depression. In this paper an algorithm is proposed that estimates the articulatory coordination of speech from audio and video signals, and uses these coordination features to learn a prediction model to track depression severity with treatment. In addition, the algorithm is able to adapt its prediction model to an individual’s baseline data in order to improve tracking accuracy. The algorithm is evaluated on two data sets. The first is the Wyss Institute Biomarkers for Depression (WIBD) multi-modal data set, which includes audio and video speech recordings. The second data set was collected by Mundt et al (2007) and contains audio speech recordings only. The data sets are comprised of patients undergoing treatment for depression as well as control subjects. In its within-subject tracking of clinical Hamilton depression (HAM-D) ratings, the algorithm achieves root mean squared error (RMSE) of 5.49 with Spearman correlation of r = 0.63 on the WIBD data set, and achieves RMSE = 5.99 with r = 0.48 on the Mundt data set.

Athletes incorporate afferent signals from the mechanoreceptors of their plantar feet to provide information about posture, stability, and joint position. Sub-threshold stochastic resonance (SR) sensory enhancing insoles have been shown to improve balance and proprioception in young and elderly participant populations. Balance and proprioception are correlated with improved athletic performance, such as agility. Agility is defined as the ability to quickly change direction. An athlete’s agility is commonly evaluated during athletic performance testing to assess their ability to participate in a competitive sporting event. Therefore, the purpose of this study was to examine the effects of SR insoles during a hexagonal agility task routinely used by coaches and sports scientists. Twenty recreational athletes were recruited to participate in this study. Each athlete was asked to perform a set of hexagonal agility trials while SR stimulation was either on or off. Vicon motion capture was used to measure feet position during six successful trials for each stimulation condition. Stimulation condition was randomized in a pairwise fashion. The study outcome measures were the task completion time and the positional accuracy of footfalls. Pairwise comparisons revealed a 0.12s decrease in task completion time (p=0.02) with no change in hopping accuracy (p=0.99) when SR stimulation was on. This is the first study to show athletic performance benefits while wearing proprioception and balance improving equipment on healthy participants. With further development, a self-contained sensory enhancing insole device could be used by recreational and professional athletes to improve movements that require rapid changes in direction.

Introduction Inclined walking while carrying a loaded backpack induces fatigue, which may destabilize gait and lead to injury. Stochastic resonance (SR) technology has been used to stabilize spatiotemporal gait characteristics of elderly individuals but has not been tested on healthy recreational athletes. Herein, we determined if sustained vigorous walking on an inclined surface while carrying a load destabilizes gait and if SR has a further effect. Methods Participants were fitted with a backpack weighing 30% of their body weight and asked to walk at a constant self-selected pace while their feet were tracked using an optical motion capture system. Their shoes were fitted with SR insoles that were set at 90% of the participant’s sensory threshold. The treadmill incline was increased every 5 min until volitional exhaustion after which the treadmill was returned to a level grade. SR stimulation was turned ON and OFF in a pairwise random fashion throughout the protocol. Spatiotemporal gait characteristics were calculated when SR was ON and OFF for the BASELINE period, the MAX perceived exertion period, and the POST period. Results Vigorous activity increases variability in the rhythmic stepping (stride time and stride length) and balance control (double support time and stride width) mechanisms of gait. Overall, SR increased stride width variability by 9% before, during, and after a fatiguing exercise. Conclusion The increased stride time and stride length variability may compromise the stability of gait during and after vigorous walking. However, participants may compensate by increasing double support time and stride width variability to maintain their stability under these adverse conditions. Furthermore, applying SR resulted in an additional increase of stride width variability and may potentially improve balance before, during, and after adverse walking conditions.

Objectives: To test whether subsensory vibratory noise applied to the sole of the foot using a novel piezoelectric vibratory insole can significantly improve sensation, enhance balance, and reduce gait variability in elderly people, as well as to determine the optimal level of vibratory noise and whether the therapeutic effect would endure and the user's sensory threshold would remain constant during the course of a day.Design: A randomized, single-blind, crossover study of 3 subsensory noise stimulation levels on 3 days.Setting: Balance and gait laboratory.Participants: Healthy community-dwelling elderly volunteers (N=12; age, 65-90y) who could feel the maximum insole vibration.Interventions: A urethane foam insole with the piezoelectric actuators delivering subsensory vibratory noise stimulation to the soles of the feet.Main Outcome Measures: Balance, gait, and timed Up and Go (TUG) test.Results: The vibratory insoles significantly improved performance on the TUG test, reduced the area of postural sway, and reduced the temporal variability of walking at both 70% and 85% of the sensory threshold and during the course of a day. Vibratory sensation thresholds remained relatively stable within and across study days.Conclusions: This study provides proof of concept that the application of the principle of stochastic resonance to the foot sole sensory system using a new low-voltage piezoelectric technology can improve measures of balance and gait that are associated with falls. Effective vibratory noise amplitudes range from 70% to 85% of the sensory threshold and can be set once daily. (C) 2015 by the American Congress of Rehabilitation Medicine

Damian G. Stephen , Bethany J. Wilcox , James B. Niemi , Jason R. Franz , Casey Kerrigan , Susan E. D’Andrea * Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States Afferent Corporation, Providence, RI, United States Department of Orthopaedics, Warren Alpert Medical School, Brown University, Providence, RI, United States Department of Physical Medicine and Rehabilitation, School of Medicine, University of Virginia, Charlottesville, VA, United States Department of Integrative Physiology, University of Colorado-Boulder, Boulder, CO, United States f JKM Technologies, LLC, Charlottesville, VA, United States g Providence VA Medical Center, Gait and Motion Analysis Laboratory, Center for Restorative and Regenerative Medicine, Providence, RI, United States

The purpose of this study was to determine whether providing subsensory stochastic-resonance mechanical vibration to the foot soles of elderly walkers could decrease gait variability. In a randomized double-blind controlled trial, 29 subjects engaged in treadmill walking while wearing sandals customized with three actuators capable of producing stochastic-resonance mechanical vibration embedded in each sole. For each subject, we determined a subsensory level of vibration stimulation. After a 5-min acclimation period of walking with the footwear, subjects were asked to walk on the treadmill for six trials, each 30 s long. Trials were pair-wise random: in three trials, actuators provided subsensory vibration; in the other trials, they did not. Subjects wore reflective markers to track body motion. Stochastic-resonance mechanical stimulation exhibited baseline-dependent effects on spatial stride-to-stride variability in gait, slightly increasing variability in subjects with least baseline variability and providing greater reductions in variability for subjects with greater baseline variability (p < .001). Thus, applying stochastic-resonance mechanical vibrations on the plantar surface of the foot reduces gait variability for subjects with more variable gait. Stochastic-resonance mechanical vibrations may provide an effective intervention for preventing falls in healthy elderly walkers.

OBJECTIVES:Previous studies have shown that subthreshold electrical or mechanical noise can reduce the sensory threshold and impart short-term improvements in sensorimotor function. We undertook this study to examine the effects of combined subsensory electrical and vibratory stimulation in conjunction with exercise training on long-term motor performance. DESIGN:Thirty subjects were recruited from adult community-dwelling stroke survivors with residual hemiparesis. Subjects were screened for residual motor ability using a functional task, and those who functioned below this level were excluded. All subjects had a history of a single unilateral ischemic or hemorrhagic stroke at least 6 mos before study entry and were not actively receiving occupational or physical therapy. Subjects were stratified by baseline upper extremity Fugl-Meyer (UEFM) (more impaired [28-35] and less impaired [36-55]) and were randomized to one of two groups: treatment (stochastic resonance stimulation [plus over minus sign] exercise: 15 subjects) and control (sham stimulation [plus over minus sign] exercise: 15 subjects). RESULTS:No significant difference was found between the stochastic resonance treatment and control group in the UEFM or in any of the secondary measures. The combined group showed modest improvements in UEFM from baseline to completion of therapy (mean improvement, 2.6 points) (P = 0.004); however, these improvements declined by 1-mo follow-up to 1.5 points (P = 0.055). No change in sensory function was detectable. CONCLUSIONS:Stochastic resonance therapy combined with occupational therapy was no more effective than occupational therapy alone in restoring sensorimotor performance. Other stochastic resonance stimulation montages or protocols might prove more effective.

Acute application of stochastic resonance (SR), defined as a subsensory level of mechanical noise presented directly to sensory neurons, improves the vibration and tactile perception in diabetic patients with mild to moderate neuropathy. This study examined the effect of 1 hour of continuous SR stimulation on sensory nerve function. Twenty diabetic patients were studied. The effect of stimulation was measured at 2 time points, at the beginning and after 60 minutes of continual SR stimulation. This effect was measured using the vibration perception threshold (VPT) at the big toe under 2 conditions: a null (no SR) condition and active SR, defined as mechanical noise below the subject's own threshold of perception. The measurements under null and active conditions were done randomly and the examiner was blinded regarding the type of condition. Immediately after SR application, the VPT with SR in null condition was similar to baseline (32.2 ± 13.1, P = nonsignificant) but was significantly lower during active SR (27.4 ± 11.9) compared with both baseline ( P = .018) and off position ( P = .045). The 60 minutes VPT with active SR (28.7 ± 11.1) reached significance comparing the baseline when one outlier was removed from the analysis ( P = .031). It may be concluded that SR for a continuous 60-minute period can sustain the VPT improvement in diabetic patients with moderate to severe neuropathy. These results permit the conclusion that there is no short-term adaptation to the stimulation signal. Long-term application of this technique, perhaps in the form of a continually vibrating shoe insert, or insole, may result in sustained improvement of nerve function.

Objective: Somatosensory function declines with diabetic neuropathy and often with stroke, resulting in diminished motor performance. Recently, it has been shown that input noise can enhance human sensorimotor function. The goal of this study was to investigate whether subsensory mechanical noise applied to the soles of the feet via vibrating insoles can be used to improve quiet-standing balance control in 15 patients with diabetic neuropathy and 15 patients with stroke. Sway data of 12 healthy elderly subjects from a previous study on vibrating insoles were added for comparison. Methods. Five traditional sway parameters and three sway parameters from random-walk analysis were computed for each trial (no noise or noise). Results: Application of noise resulted in a statistically significant reduction in each of the eight sway parameters in the subjects with diabetic neuropathy, the subjects with stroke, and the elderly subjects. We also found that higher levels of baseline postural sway in sensory-impaired individuals was correlated with greater improvements in balance control with input noise. Interpretation This work indicates that noise-based devices could ameliorate diabetic and stroke impairments in balance control.

omatosensory feedback is an important component of the balance control system. Older adults, patients with diabetic neuropathy, and patients with stroke exhibit a marked deficit in the perception of cutaneous and proprioceptive stimuli (e.g., see [1] and references therein). Such changes to the somatosensory system, which have been associated with increases in mechanoreceptor detection thresholds , may predispose individuals to falls, which are the most common cause of morbidity and mortality among older persons. Accordingly, there is a pressing need to develop bioengi-neering techniques and devices that improve sensorimotor function in older adults and patients with sensory deficits. Recently, it has been shown that noise can enhance the detection and transmission of weak signals in certain nonlinear systems, via a mechanism known as stochastic resonance (SR). The phenomenon of SR, which is counterintuitive given that noise has traditionally been viewed as a detriment to signal detection and transmission, is based on the concept that the flow of information through a system can be maximized by the presence of a particular, nonzero level of noise. SR was originally proposed in the context of global climate modeling as a possible explanation for the periodic recurrences of the Earth's ice ages [2], [3]. Since then, SR-type dynamics have been demonstrated in a variety of physical and biological systems [4]-[10], including rat cutaneous afferents [11] and human muscle spindles [12]. In this article, we review our work on using input noise (mechanical and electrical, respectively) to enhance somatosensation in humans [1], [13]-[16] and improve the performance of the human balance control system [17], [18]. We also discuss bioengineering applications and future directions for SR-based techniques and devices. As a first effort in this area, we designed a study to examine the effects of input noise on tactile sensation in humans. Specifically , we were interested in studying noise-mediated changes in the perception of subthreshold tactile stimuli. We hypothesized that the ability of an individual to detect a subthreshold tactile stimulus can be significantly enhanced by the presence of a particular, nonzero level of noise [13], [14]. To test this hypothesis, we conducted psychophysical experiments on ten healthy young subjects (age 18-31 years, mean 25 years). Local indentations were applied to the tip of each subject's right middle digit using a cylindrical probe (Figure 1). The protocol consisted of the presentation of: a) a subthreshold mechanical stimulus plus mechanical noise, or b) no mechanical stimulus …