Exploration of physiological sensors, features, and machine learning models for pain intensity estimation.

In current clinical settings, typically pain is measured by a patient's self-reported information. This subjective pain assessment results in suboptimal treatment plans, over-prescription of opioids, and drug-seeking behavior among patients. In the present study, we explored automatic objective pain intensity estimation machine learning models using inputs from physiological sensors. This study uses BioVid Heat Pain Dataset. We extracted features from Electrodermal Activity (EDA), Electrocardiogram (ECG), Electromyogram (EMG) signals collected from study participants subjected to heat pain. We built different machine learning models, including Linear Regression, Support Vector Regression (SVR), Neural Networks and Extreme Gradient Boosting for continuous value pain intensity estimation. Then we identified the physiological sensor, feature set and machine learning model that give the best predictive performance. We found that EDA is the most information-rich sensor for continuous pain intensity prediction. A set of only 3 features from EDA signals using SVR model gave an average performance of 0.93 mean absolute error (MAE) and 1.16 root means square error (RMSE) for the subject-independent model and of 0.92 MAE and 1.13 RMSE for subject-dependent. The MAE achieved with signal-feature-model combination is less than 1 unit on 0 to 4 continues pain scale, which is smaller than the MAE achieved by the methods reported in the literature. These results demonstrate that it is possible to estimate pain intensity of a patient using a computationally inexpensive machine learning model with 3 statistical features from EDA signal which can be collected from a wrist biosensor. This method paves a way to developing a wearable pain measurement device.

Towards non-invasive heart rate monitoring in free-ranging cetaceans: a unipolar suction cup tag measured the heart rate of trained Risso's dolphins.

Heart rate monitoring in free-ranging cetaceans to understand their behavioural ecology and diving physiology is challenging. Here, we developed a simple, non-invasive method to monitor the heart rate of cetaceans in the field using an electrocardiogram-measuring device and a single suction cup equipped with an electrode. The unipolar suction cup was placed on the left lateral body surface behind the pectoral fin of Risso's dolphins (Grampus griseus) and a false killer whale (Pseudorca crassidens) in captivity; their heart rate was successfully monitored. We observed large heart rate oscillations corresponding to respiration in the motionless whales during surfacing (a false killer whale, mean 47 bpm, range 20-75 bpm; Risso's dolphins, mean ± s.d. 61 ± 15 bpm, range 28-120 bpm, n = 4 individuals), which was consistent with the sinus arrhythmia pattern (eupneic tachycardia and apneic bradycardia) observed in other cetaceans. Immediately after respiration, the heart rate rapidly increased to approximately twice that observed prior to the breath. Heart rate then gradually decreased at around 20-50 s and remained relatively constant until the next breath. Furthermore, we successfully monitored the heart rate of a free-swimming Risso's dolphin. The all-in-one suction cup device is feasible for field use without restraining animals and is helpful in further understanding the diving physiology of free-ranging cetaceans. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.

Out of the laboratory, into the field: perspectives on social, ethical and regulatory challenges in UK wildlife research.

Drawing on insights from qualitative social science research, this paper aims to prompt reflection on social, ethical and regulatory challenges faced by scientists undertaking invasive animal research in the field and propose ways of addressing these challenges to promote good care for animals and environments. In particular, we explore challenges relating to the management of (i) relationships with publics and stakeholders, who may be present at field sites or crucial to research success; (ii) ethical considerations not present in the laboratory, such as the impacts of research on populations and ecosystems; (iii) working under an array of regulations, which may operate in accordance with competing ethical principles or objectives; and (iv) relationships with regulators (especially vets), which may involve disagreements over ethics and expertise, especially because regulators may be more accustomed to overseeing research in the laboratory than the field. We argue that flexibility-at a personal and policy level-and respect for others' expertise emerged as two key ways of negotiating ethical challenges, fostering positive working relationships and promoting good care for individual animals and broader ecosystems. While our analysis focuses on the UK, we propose that many of these lessons are broadly applicable to international contexts. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.

A brief introduction to the analysis of time-series data from biologging studies.

Recent advances in tagging and biologging technology have yielded unprecedented insights into wild animal physiology. However, time-series data from such wild tracking studies present numerous analytical challenges owing to their unique nature, often exhibiting strong autocorrelation within and among samples, low samples sizes and complicated random effect structures. Gleaning robust quantitative estimates from these physiological data, and, therefore, accurate insights into the life histories of the animals they pertain to, requires careful and thoughtful application of existing statistical tools. Using a combination of both simulated and real datasets, I highlight the key pitfalls associated with analysing physiological data from wild monitoring studies, and investigate issues of optimal study design, statistical power, and model precision and accuracy. I also recommend best practice approaches for dealing with their inherent limitations. This work will provide a concise, accessible roadmap for researchers looking to maximize the yield of information from complex and hard-won biologging datasets. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.

Animal tag technology keeps coming of age: an engineering perspective.

Animal-borne tags (biologgers) have now become extremely sophisticated, recording data from multiple sensors at high frequencies for long periods and, as such, have become a powerful tool for behavioural ecologists and physiologists studying wild animals. But the design and implementation of these tags is not trivial because engineers have to maximize performance and ability to function under onerous conditions while minimizing tag mass and volume (footprint) to maximize the wellbeing of the animal carriers. We present some of the major issues faced by tag engineers and show how tag designers must accept compromises while maintaining systems that can answer the questions being posed. We also argue that basic understanding of engineering issues in tag design by biologists will help feedback to engineers to better tag construction but also reduce the likelihood that tag-deploying biologists will misunderstand their own results. Finally, we suggest that proper consideration of conventional technology together with new approaches will lead to further step changes in our understanding of wild-animal biology using smart tags. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.

What is physiologging? Introduction to the theme issue, part 2.

The physiological mechanisms by which animals regulate energy expenditure, respond to stimuli and stressors, and maintain homeostasis at the tissue, organ and whole organism levels can be described by 'physiologging'-that is, the use of onboard miniature electronic devices to record physiological metrics of animals in captivity or free-living in the wild. Despite its origins in the 1960s, physiologging has evolved more slowly than its umbrella field of biologging. However, the recording of physiological metrics in free-living animals will be key to solving some of the greatest challenges in biodiversity conservation, issues pertaining to animal health and welfare, and for inspiring future therapeutic strategies for human health. Current physiologging technologies encompass the measurement of physiological variables such as heart rate, brain activity, body temperature, muscle stimulation and dynamic movement, yet future developments will allow for onboard logging of metrics relating to organelle, molecular and genetic function. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.

Future trends in measuring physiology in free-living animals.

Thus far, ecophysiology research has predominantly been conducted within controlled laboratory-based environments, owing to a mismatch between the recording technologies available for physiological monitoring in wild animals and the suite of behaviours and environments they need to withstand, without unduly affecting subjects. While it is possible to record some physiological variables for free-living animals using animal-attached logging devices, including inertial-measurement, heart-rate and temperature loggers, the field is still in its infancy. In this opinion piece, we review the most important future research directions for advancing the field of 'physiologging' in wild animals, including the technological development that we anticipate will be required, and the fiscal and ethical challenges that must be overcome. Non-invasive, multi-sensor miniature devices are ubiquitous in the world of human health and fitness monitoring, creating invaluable opportunities for animal and human physiologging to drive synergistic advances. We argue that by capitalizing on the research efforts and advancements made in the development of human wearables, it will be possible to design the non-invasive loggers needed by ecophysiologists to collect accurate physiological data from free-ranging animals ethically and with an absolute minimum of impact. In turn, findings have the capacity to foster transformative advances in human health monitoring. Thus, we invite biomedical engineers and researchers to collaborate with the animal-tagging community to drive forward the advancements necessary to realize the full potential of both fields. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.

Shining new light on sensory brain activation and physiological measurement in seals using wearable optical technology.

Sensory ecology and physiology of free-ranging animals is challenging to study but underpins our understanding of decision-making in the wild. Existing non-invasive human biomedical technology offers tools that could be harnessed to address these challenges. Functional near-infrared spectroscopy (fNIRS), a wearable, non-invasive biomedical imaging technique measures oxy- and deoxyhaemoglobin concentration changes that can be used to detect localized neural activation in the brain. We tested the efficacy of fNIRS to detect cortical activation in grey seals (Halichoerus grypus) and identify regions of the cortex associated with different senses (vision, hearing and touch). The activation of specific cerebral areas in seals was detected by fNIRS in responses to light (vision), sound (hearing) and whisker stimulation (touch). Physiological parameters, including heart and breathing rate, were also extracted from the fNIRS signal, which allowed neural and physiological responses to be monitored simultaneously. This is, to our knowledge, the first time fNIRS has been used to detect cortical activation in a non-domesticated or laboratory animal. Because fNIRS is non-invasive and wearable, this study demonstrates its potential as a tool to quantitatively investigate sensory perception and brain function while simultaneously recording heart rate, tissue and arterial oxygen saturation of haemoglobin, perfusion changes and breathing rate in free-ranging animals. This article is part of the theme issue 'Measuring physiology in free-living animals (Part I)'.

An engineering perspective on the development and evolution of implantable cardiac monitors in free-living animals.

The latest technologies associated with implantable physiological monitoring devices can record multiple channels of data (including: heart rates and rhythms, activity, temperature, impedance and posture), and coupled with powerful software applications, have provided novel insights into the physiology of animals in the wild. This perspective details past challenges and lessons learned from the uses and developments of implanted biologgers designed for human clinical application in our research on free-ranging American black bears (Ursus americanus). In addition, we reference other research by colleagues and collaborators who have leveraged these devices in their work, including: brown bears (Ursus arctos), grey wolves (Canis lupus), moose (Alces alces), maned wolves (Chrysocyon brachyurus) and southern elephant seals (Mirounga leonina). We also discuss the potentials for applications of such devices across a range of other species. To date, the devices described have been used in fifteen different wild species, with publications pending in many instances. We have focused our physiological research on the analyses of heart rates and rhythms and thus special attention will be paid to this topic. We then discuss some major expected step changes such as improvements in sensing algorithms, data storage, and the incorporation of next-generation short-range wireless telemetry. The latter provides new avenues for data transfer, and when combined with cloud-based computing, it not only provides means for big data storage but also the ability to readily leverage high-performance computing platforms using artificial intelligence and machine learning algorithms. These advances will dramatically increase both data quantity and quality and will facilitate the development of automated recognition of extreme physiological events or key behaviours of interest in a broad array of environments, thus further aiding wildlife monitoring and management. This article is part of the theme issue 'Measuring physiology in free-living animals (Part I)'.

Introduction to the theme issue: Measuring physiology in free-living animals.

By describing where animals go, biologging technologies (i.e. animal attached logging of biological variables with small electronic devices) have been used to document the remarkable athletic feats of wild animals since the 1940s. The rapid development and miniaturization of physiologging (i.e. logging of physiological variables such as heart rate, blood oxygen content, lactate, breathing frequency and tidal volume on devices attached to animals) technologies in recent times (e.g. devices that weigh less than 2 g mass that can measure electrical biopotentials for days to weeks) has provided astonishing insights into the physiology of free-living animals to document how and why wild animals undertake these extreme feats. Now, physiologging, which was traditionally hindered by technological limitations, device size, ethics and logistics, is poised to benefit enormously from the on-going developments in biomedical and sports wearables technologies. Such technologies are already improving animal welfare and yield in agriculture and aquaculture, but may also reveal future pathways for therapeutic interventions in human health by shedding light on the physiological mechanisms with which free-living animals undertake some of the most extreme and impressive performances on earth. This article is part of the theme issue 'Measuring physiology in free-living animals (Part I)'.

A non-invasive system to measure heart rate in hard-shelled sea turtles: potential for field applications.

To measure the heart rate of unrestrained sea turtles, it has been believed that a probe must be inserted inside the body owing to the presence of the shell. However, inserting the probe is invasive and difficult to apply to animals in the field. Here, we have developed a non-invasive heart rate measurement method for some species of sea turtles. In our approach, an electrocardiogram (ECG) was performed using an animal-borne ECG recorder and two electrodes-which were electrically insulated from seawater-pasted on the carapace. Based on the measured ECG, the heartbeat signals were identified with an algorithm using a band-pass filter. We implemented this algorithm in a user-friendly program package, ECGtoHR. In experiments conducted in a water tank and in a lagoon, we successfully measured the heart rate of loggerhead, olive ridley and black turtles, but not green and hawksbill turtles. The average heart rate of turtles when resting underwater was 6.2 ± 1.9 beats min-1 and that when moving at the surface was 14.0 ± 2.4 beats min-1. Our approach is particularly suitable for endangered species such as sea turtles, and has the potential to be extended to a variety of other free-ranging species. This article is part of the theme issue 'Measuring physiology in free-living animals (Part I)'.

Navigation of a Freely Walking Fruit Fly in Infinite Space Using a Transparent Omnidirectional Locomotion Compensator (TOLC).

Animal behavior is an essential element in behavioral neuroscience study. However, most behavior studies in small animals such as fruit flies (Drosophilamelanogaster) have been performed in a limited spatial chamber or by tethering the fly's body on a fixture, which restricts its natural behavior. In this paper, we developed the Transparent Omnidirectional Locomotion Compensator (TOLC) for a freely walking fruit fly without tethering, which enables its navigation in infinite space. The TOLC maintains a position of a fruit fly by compensating its motion using the transparent sphere. The TOLC is capable of maintaining the position error < 1 mm for 90.3% of the time and the heading error < 5° for 80.2% of the time. The inverted imaging system with a transparent sphere secures the space for an additional experimental apparatus. Because the proposed TOLC allows us to observe a freely walking fly without physical tethering, there is no potential injury during the experiment. Thus, the TOLC will offer a unique opportunity to investigate longitudinal studies of a wide range of behavior in an unrestricted walking Drosophila.

Self-adhesive protein/polypyrrole hybrid film for flexible electronic sensors in physiological signal monitoring.

Flexible electronic sensors composed of conductive material and flexible film have attracted increasing attention in decades due to its commercial, medical and scientific value. However, the poor interfacial bonding robustness between conductive materials and flexible film influences widely practical application of sensors. It is still a great challenge to fabricate a self-adhesive conductive film. Herein, we report a freestanding and self-adhesive bovine serum albumin/polypyrrole (BSA/PPy) hybrid film at the air/water interface. It is discovered that the PPy nanoparticles aggregate uniformly on the BSA film that is formed by amyloid-like BSA aggregation. The BSA/PPy film was integrated with polydimethylsiloxane (PDMS) film to fabricate flexible electronic sensors. The test indicates that the BSA/PPy film-based sensor could tolerate 500 cycles of bending without the resistance performance variation. The BSA/PPy film functions as a key mediator to dynamically tune the PPy conductance in response to external pressures and strains. The sensors exhibit ability for detecting tiny acoustic vibration, real-time human motion, physiological behavior and for differentiating various breathing pattern. Our strategy may open a pathway to readily construct flexible electronic sensors toward practical applications.

Multiorgan-on-a-Chip: A Systemic Approach To Model and Decipher Inter-Organ Communication.

Multiorgan-on-a-chip (multi-OoC) platforms have great potential to redefine the way in which human health research is conducted. After briefly reviewing the need for comprehensive multiorgan models with a systemic dimension, we highlight scenarios in which multiorgan models are advantageous. We next overview existing multi-OoC platforms, including integrated body-on-a-chip devices and modular approaches involving interconnected organ-specific modules. We highlight how multi-OoC models can provide unique information that is not accessible using single-OoC models. Finally, we discuss remaining challenges for the realization of multi-OoC platforms and their worldwide adoption. We anticipate that multi-OoC technology will metamorphose research in biology and medicine by providing holistic and personalized models for understanding and treating multisystem diseases.

From 3D Back to 2D Monolayer Stomach Organoids-on-a-Chip.

2D monolayer gastric organoids (2DMGOs)-on-a-chip have consistent structures and can live for more than a year in culture. This state-of-the-art cell physiological system in a microfluidic device provides a way to investigate biomedically relevant, stimuli-dependent cellular responses in a variety of differentiated 2DMGOs.

Deciphering Organoids: High-Dimensional Analysis of Biomimetic Cultures.

Organoids are self-organising stem cell-derived ex vivo cultures widely adopted as biomimetic models of healthy and diseased tissues. Traditional low-dimensional experimental methods such as microscopy and bulk molecular analysis have generated remarkable biological insights from organoids. However, as complex heterocellular systems, organoids are especially well-positioned to take advantage of emerging high-dimensional technologies. In particular, single-cell methods offer considerable opportunities to analyse organoids at unprecedented scale and depth, enabling comprehensive characterisation of cellular processes and spatial organisation underpinning organoid heterogeneity. This review evaluates state-of-the-art analytical methods applied to organoids, discusses the latest advances in single-cell technologies, and speculates on the integration of these two rapidly developing fields.

Intragastric satiety-inducing device reduces food intake and suppresses body weight gain in a rodent model.

BACKGROUND: An intragastric satiety-inducing device (ISD) (Full Sense Device; Baker, Foote, Kemmeter, Walburn, LLC, Grand Rapids, MI) is a novel weight-loss device, which may induce satiety by applying continuous pressure on the gastric cardia. This study investigated the effect of the ISD on food intake and body weight gain in a rodent model. METHODS: Thirty-two male Sprague-Dawley rats (weight, 250-300 g) were randomly divided into four groups of eight individuals. Single-disk (SD) and double-disk (DD) group animals underwent peroral placement of a single- or double-disk ISD, respectively, under fluoroscopic guidance. The ISD comprised a 4 mm × 1.5 cm nitinol stent placed in the lower esophagus and one (single-disk) or two (double-disk) 2.5-cm-diameter star-shaped nitinol disks placed in the gastric fundus. Esophageal stent (ES) and sham-operated (SO) group animals underwent peroral placement of the ES part of the ISD and a sham operation, respectively. RESULTS: Food intake was significantly different among the four groups over the 4-week study period (P < 0.001); food intake was significantly lower in the SD and DD groups than in the SO group (P = 0.016 and P = 0.002, respectively) but was not significantly different between the SD and DD groups (P > 0.999) and between the ES and SO groups (P = 0.677). Body weight was significantly different among the four groups by the end of the study period (P < 0.001); body weight was significantly lower in the DD group than in the SD, ES, and SO groups (P = 0.010, P < 0.001, and P < 0.001, respectively) and in the SD group than in the SO group (P = 0.001), but it was not significantly different between the ES and SO groups (P = 0.344). CONCLUSION: ISD reduced food intake and suppressed body weight gain in a rodent model.

A Modified Protocol for Cortisol Analysis in Zebrafish (Danio rerio), Individual Embryos, and Larvae.

A modified protocol for the extraction and analysis of cortisol in individual zebrafish, Danio rerio, embryo, and larva samples has been developed and evaluated. Recovery efficiency of the method was high, specifically calculated at 93.8% ± 6.5%. Dilution tests showed high parallelism, while increasing the number of individuals used in each extraction sample resulted in a linear, although slightly underestimated, increase of cortisol yield. Results of cortisol content from 0, 3, and 5 days postfertilization (dpf) fish using the proposed protocol were within the range of most published studies analyzing cortisol in pooled samples of 10-30 individuals. Moreover, 5 dpf larvae had significantly higher cortisol levels than embryos, a pattern commonly observed in literature. Finally, application of an osmotic stress in 5 dpf larvae led to a statistically significant increase in cortisol content.

Absolute and relative reliability of several measures of static postural stability calculated using a GYKO inertial sensor system.

PURPOSE: The aim of this study was to analyse absolute and relative reliability of a number of postural static stability measures obtained from a GYKO inertial sensor system in young adults. METHODS: The study examined 29 healthy non-athlete young adults. A test was performed for 30 s while standing on one foot, without moving, with eyes open and arms relaxed along the sides of the body. The examinations were performed twice, with a one-week interval. Relative reliability was measured using the intraclass correlation coefficient (ICC) and the 95% confidence interval (95% CI), whereas the absolute reliability was evaluated based on the standard error of measurement (SEM) and the minimal detectable change (MDC). RESULTS: The results of this study showed moderate to good relative reliability scores for all the postural stability measures, with ICC values ranging from 0.62 to 0.70. For most of the analysed variables, SEM% ranged from ca. 10 to 14%. Relatively high SEM% values were obtained only for two variables (Area, Convex Hull Area). CONCLUSIONS: The low costs of GYKO inertial sensor systems, the fast and easy installation, the mobility and high reliability of the measurement of postural stability show that it can be effective alternative to stabilographic platforms.

Practical implications of the 2019 Nobel Prize in Physiology or Medicine: from molecular adaptation to hypoxia to novel anti-anemic drugs in the clinic.

The 2019 Nobel Prize for Medicine or Physiology was assigned to three prestigious physician-scientists, Gregg L. Semenza, William G. Kaelin, and Peter J. Ratcliffe, who clarified the molecular mechanisms of hypoxia adaptation. This viewpoint traces their fundamental findings, which have paved the way for the development of innovative drugs for a wide range of common diseases, including cancer and anemia.