Internet of Things for beyond-the-laboratory prosthetics research.

Research on upper-limb prostheses is typically laboratory-based. Evidence indicates that research has not yet led to prostheses that meet user needs. Inefficient communication loops between users, clinicians and manufacturers limit the amount of quantitative and qualitative data that researchers can use in refining their innovations. This paper offers a first demonstration of an alternative paradigm by which remote, beyond-the-laboratory prosthesis research according to user needs is feasible. Specifically, the proposed Internet of Things setting allows remote data collection, real-time visualization and prosthesis reprogramming through Wi-Fi and a commercial cloud portal. Via a dashboard, the user can adjust the configuration of the device and append contextual information to the prosthetic data. We evaluated this demonstrator in real-time experiments with three able-bodied participants. Results promise the potential of contextual data collection and system update through the internet, which may provide real-life data for algorithm training and reduce the complexity of send-home trials. This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.

Highly Deformed o-Carborane Functionalised Non-linear Polycyclic Aromatics with Exceptionally Long C-C Bonds.

The effect of substituting o-carborane into the most sterically hindered positions of phenanthrene and benzo(k)tetraphene is reported. Synthesised via a Bull-Hutchings-Quayle benzannulation, the crystal structures of these non-linear acenes exhibited the highest aromatic deformation parameters observed for any reported carborane compound to date, and among the largest carboranyl C-C bond length of all organo-substituted o-carboranes. Photoluminescence studies of these compounds demonstrated efficient intramolecular charge-transfer, leading to aggregation induced emission properties. Additionally, an unusual low-energy excimer was observed for the phenanthryl compound. These are two new members of the family of carborane-functionalised non-linear acenes, notable for their peculiar structures and multi-luminescent properties.

Arduino-Based Myoelectric Control: Towards Longitudinal Study of Prosthesis Use.

Understanding how upper-limb prostheses are used in daily life helps to improve the design and robustness of prosthesis control algorithms and prosthetic components. However, only a very small fraction of published research includes prosthesis use in community settings. The cost, limited battery life, and poor generalisation may be the main reasons limiting the implementation of home-based applications. In this work, we introduce the design of a cost-effective Arduino-based myoelectric control system with wearable electromyogram (EMG) sensors. The design considerations focused on home studies, so the robustness, user-friendly control adjustments, and user supports were the main concerns. Three control algorithms, namely, direct control, abstract control, and linear discriminant analysis (LDA) classification, were implemented in the system. In this paper, we will share our design principles and report the robustness of the system in continuous operation in the laboratory. In addition, we will show a first real-time implementation of the abstract decoder for prosthesis control with an able-bodied participant.

Carborane-Induced Excimer Emission of Severely Twisted Bis-o-Carboranyl Chrysene.

The synthesis of a highly twisted chrysene derivative incorporating two electron deficient o-carboranyl groups is reported. The molecule exhibits a complex, excitation-dependent photoluminescence, including aggregation-induced emission (AIE) with good quantum efficiency and an exceptionally long singlet excited state lifetime. Through a combination of detailed optical studies and theoretical calculations, the excited state species are identified, including an unusual excimer induced by the presence of o-carborane. This is the first time that o-carborane has been shown to induce excimer formation ab initio, as well as the first observation of excimer emission by a chrysene-based small molecule in solution. Bis-o-carboranyl chrysene is thus an initial member of a new family of o-carboranyl phenacenes exhibiting a novel architecture for highly-efficient multi-luminescent fluorophores.

Altered retinoid signaling compromises decidualization in human endometriotic stromal cells.

Decidualization alters multiple molecular pathways in endometrium to permit successful embryo implantation. We have reported that paracrine factors, including retinoids, secreted from progesterone-treated endometrial stromal cells, act on nearby epithelial cells to induce the estradiol metabolizing enzyme HSD17B2. This same induction is not seen in endometriotic stromal cells. We have also shown significant differences in retinoid uptake, metabolism and action in endometriotic tissue and stromal cells compared to normal endometrium. Here, we characterize retinoid signaling during decidualization in these cells. Endometrial and endometriotic cells were isolated, cultured and incubated and decidualized. Genes involved in retinoid metabolism and trafficking were examined using RT-PCR and Western blotting. Prolactin, a decidualization marker, was also examined. We found that both endometrial and endometriotic stromal cells express all intracellular proteins involved in retinoid uptake and metabolism. Decidualization significantly reduced the expression of the genes responsible for retinoid uptake and shuttling to the nucleus. However, expression of CRBP1, an intracellular carrier protein for retinol, increased, as did RBP4, a carrier protein for retinol in the blood, which can function in a paracrine manner. Secreted RBP4 was detected in the media from decidualized endometrial cells but not from endometriotic cells. We believe that retinoid trafficking in endometrial stromal cells during decidualization may shift to favor paracrine rather than intracrine signaling, which may enhance signaling to the adjacent epithelium. There is blunting of this signaling in endometriotic cells. These alterations in retinoid signaling may help explain the decidualization defects and deficient estradiol inactivation (via HSD17B2) seen in endometriosis.

Genome-wide DNA methylation analysis predicts an epigenetic switch for GATA factor expression in endometriosis.

Endometriosis is a gynecological disease defined by the extrauterine growth of endometrial-like cells that cause chronic pain and infertility. The disease is limited to primates that exhibit spontaneous decidualization, and diseased cells are characterized by significant defects in the steroid-dependent genetic pathways that typify this process. Altered DNA methylation may underlie these defects, but few regions with differential methylation have been implicated in the disease. We mapped genome-wide differences in DNA methylation between healthy human endometrial and endometriotic stromal cells and correlated this with gene expression using an interaction analysis strategy. We identified 42,248 differentially methylated CpGs in endometriosis compared to healthy cells. These extensive differences were not unidirectional, but were focused intragenically and at sites distal to classic CpG islands where methylation status was typically negatively correlated with gene expression. Significant differences in methylation were mapped to 403 genes, which included a disproportionally large number of transcription factors. Furthermore, many of these genes are implicated in the pathology of endometriosis and decidualization. Our results tremendously improve the scope and resolution of differential methylation affecting the HOX gene clusters, nuclear receptor genes, and intriguingly the GATA family of transcription factors. Functional analysis of the GATA family revealed that GATA2 regulates key genes necessary for the hormone-driven differentiation of healthy stromal cells, but is hypermethylated and repressed in endometriotic cells. GATA6, which is hypomethylated and abundant in endometriotic cells, potently blocked hormone sensitivity, repressed GATA2, and induced markers of endometriosis when expressed in healthy endometrial cells. The unique epigenetic fingerprint in endometriosis suggests DNA methylation is an integral component of the disease, and identifies a novel role for the GATA family as key regulators of uterine physiology-aberrant DNA methylation in endometriotic cells correlates with a shift in GATA isoform expression that facilitates progesterone resistance and disease progression.

Paracrine activation of WNT/ß-catenin pathway in uterine leiomyoma stem cells promotes tumor growth.

Uterine leiomyomas are extremely common estrogen and progesterone-dependent tumors of the myometrium and cause irregular uterine bleeding, severe anemia, and recurrent pregnancy loss in 15-30% of reproductive-age women. Each leiomyoma is thought to arise from a single mutated myometrial smooth muscle stem cell. Leiomyoma side-population (LMSP) cells comprising 1% of all tumor cells and displaying tumor-initiating stem cell characteristics are essential for estrogen- and progesterone-dependent in vivo growth of tumors, although they have remarkably lower estrogen/progesterone receptor levels than mature myometrial or leiomyoma cells. However, how estrogen/progesterone regulates the growth of LMSP cells via mature neighboring cells is unknown. Here, we demonstrate a critical paracrine role of the wingless-type (WNT)/ß-catenin pathway in estrogen/progesterone-dependent tumorigenesis, involving LMSP and differentiated myometrial or leiomyoma cells. Estrogen/progesterone treatment of mature myometrial cells induced expression of WNT11 and WNT16, which remained constitutively elevated in leiomyoma tissues. In LMSP cells cocultured with mature myometrial cells, estrogen-progesterone selectively induced nuclear translocation of ß-catenin and induced transcriptional activity of its heterodimeric partner T-cell factor and their target gene AXIN2, leading to the proliferation of LMSP cells. This effect could be blocked by a WNT antagonist. Ectopic expression of inhibitor of ß-catenin and T-cell factor 4 in LMSP cells, but not in mature leiomyoma cells, blocked the estrogen/progesterone-dependent growth of human tumors in vivo. We uncovered a paracrine role of the WNT/ß-catenin pathway that enables mature myometrial or leiomyoma cells to send mitogenic signals to neighboring tissue stem cells in response to estrogen and progesterone, leading to the growth of uterine leiomyomas.

Online extraction and single trial analysis of regions contributing to erroneous feedback detection.

Understanding how the brain processes errors is an essential and active field of neuroscience. Real time extraction and analysis of error signals provide an innovative method of assessing how individuals perceive ongoing interactions without recourse to overt behaviour. This area of research is critical in modern Brain-Computer Interface (BCI) design, but may also open fruitful perspectives in cognitive neuroscience research. In this context, we sought to determine whether we can extract discriminatory error-related activity in the source space, online, and on a trial by trial basis from electroencephalography data recorded during motor imagery. Using a data driven approach, based on interpretable inverse solution algorithms, we assessed the extent to which automatically extracted error-related activity was physiologically and functionally interpretable according to performance monitoring literature. The applicability of inverse solution based methods for automatically extracting error signals, in the presence of noise generated by motor imagery, was validated by simulation. Representative regions of interest, outlining the primary generators contributing to classification, were found to correspond closely to networks involved in error detection and performance monitoring. We observed discriminative activity in non-frontal areas, demonstrating that areas outside of the medial frontal cortex can contribute to the classification of error feedback activity.

Reducing Motor Variability Enhances Myoelectric Control Robustness Across Untrained Limb Positions.

The limb position effect is a multi-faceted problem, associated with decreased upper-limb prosthesis control acuity following a change in arm position. Factors contributing to this problem can arise from distinct environmental or physiological sources. Despite their differences in origin, the effect of each factor manifests similarly as increased input data variability. This variability can cause incorrect decoding of user intent. Previous research has attempted to address this by better capturing input data variability with data abundance. In this paper, we take an alternative approach and investigate the effect of reducing trial-to-trial variability by improving the consistency of muscle activity through user training. Ten participants underwent 4 days of myoelectric training with either concurrent or delayed feedback in a single arm position. At the end of training participants experienced a zero-feedback retention test in multiple limb positions. In doing so, we tested how well the skill learned in a single limb position generalized to untrained positions. We found that delayed feedback training led to more consistent muscle activity across both the trained and untrained limb positions. Analysis of patterns of activations in the delayed feedback group suggest a structured change in muscle activity occurs across arm positions. Our results demonstrate that myoelectric user-training can lead to the retention of motor skills that bring about more robust decoding across untrained limb positions. This work highlights the importance of reducing motor variability with practice, prior to examining the underlying structure of muscle changes associated with limb position.

Evidencing the effectiveness of upper limb prostheses: a multi-stakeholder perspective on study requirements.

The provision of upper limb prosthetic devices through the National Health Services (NHS) within the United Kingdom is driven by national policies. NHS England have recently published a new policy to provide multi-grip myoelectric hands. The policy highlighted that there was limited evidence to support its deployment and it will be reviewed should new information arise. The clear identification of the evidence gap provides an opportunity for the academic research community to conduct studies that will inform future iterations of this and other upper limb prosthetic related policies. This paper presents a summary of findings and recommendations based on two multi-stakeholder workshops held in June 2022 and July 2022, which explored the design requirements for policy-driven research studies. The workshops involved people from a broad range of stakeholder groups: policy, academia, NHS clinical and management, industry, and a person with upper limb absence. The workshop discussions focused on the research questions that NHS England identified in the policy evidence review: (1) Clinical Effectiveness; (2) Cost Effectiveness; (3) Safety; and (4) Patient Subgroups. The recommendations based on stakeholder discussions included the need to gather qualitative and quantitative research evidence, use goal-based outcome measures, and conduct longitudinal studies. Future research studies also need to address the complexities of conducting national and international policy-driven research, such as clinical resource capacity and participant involvement.

Delaying feedback during pre-device training facilitates the retention of novel myoelectric skills: a laboratory and home-based study.

Objective.The objective of this study was to assess the impact of delayed feedback training on the retention of novel myoelectric skills, and to demonstrate the use of this training approach in the home environment.Approach.We trained limb-intact participants to use a motor learning-based upper-limb prosthesis control scheme called abstract decoding. A delayed feedback paradigm intended to prevent within-trial adaptation and to facilitate motor learning was used. We conducted two multi-day experiments. Experiment 1 was a laboratory-based study consisting of two groups trained over a 4 day period with concurrent or delayed feedback. An additional follow-up session took place after 18 days to assess the retention of motor skills. Experiment 2 was a home-based pilot study that took place over five consecutive days to investigate delayed feedback performance when using bespoke training structures.Main Results.Approximately 35 000 trials were collected across both experiments. Experiment 1 found that the retention of motor skills for the delayed feedback group was significantly better than that of their concurrent feedback counterparts. In addition, the delayed feedback group improved their retention of motor skills across days, whereas the concurrent feedback group did not. Experiment 2 demonstrated that by using a bespoke training protocol in an environment that is more conducive to learning, it is possible for participants to become highly accurate in the absence of feedback.Significance.These results show that with delayed feedback training, it is possible to retain novel myoelectric skills. Using abstract decoding participants can activate four distinct muscle patterns without using complex algorithms. The accuracy achieved in the pilot study supports the feasibility of motor learning-based upper-limb prosthesis control after home-based myoelectric training.

Vitality surveillance at distance using thin-film tandem-like narrowband near-infrared photodiodes with light-enhanced responsivity.

Remote measurement of vital sign parameters like heartbeat and respiration rate represents a compelling challenge in monitoring an individual's health in a noninvasive way. This could be achieved by large field-of-view, easy-to-integrate unobtrusive sensors, such as large-area thin-film photodiodes. At long distances, however, discriminating weak light signals from background disturbance demands superior near-infrared (NIR) sensitivity and optical noise tolerance. Here, we report an inherently narrowband solution-processed, thin-film photodiode with ultrahigh and controllable NIR responsivity based on a tandem-like perovskite-organic architecture. The device has low dark currents (<10-6 mA cm-2), linear dynamic range >150 dB, and operational stability over time (>8 hours). With a narrowband quantum efficiency that can exceed 200% at 850 nm and intrinsic filtering of other wavelengths to limit optical noise, the device exhibits higher tolerance to background light than optically filtered silicon-based sensors. We demonstrate its potential in remote monitoring by measuring the heart rate and respiration rate from distances up to 130 cm in reflection.

Identification of the Origin of Ultralow Dark Currents in Organic Photodiodes.

Organic bulk heterojunction photodiodes (OPDs) attract attention for sensing and imaging. Their detectivity is typically limited by a substantial reverse bias dark current density (Jd ). Recently, using thermal admittance or spectral photocurrent measurements, Jd has been attributed to thermal charge generation mediated by mid-gap states. Here, the temperature dependence of Jd in state-of-the-art OPDs is reported with Jd down to 10-9  mA cm-2 at -0.5 V bias. For a variety of donor-acceptor bulk-heterojunction blends it is found that the thermal activation energy of Jd is lower than the effective bandgap of the blends, by ca. 0.3 to 0.5 eV, but higher than expected for mid-gap states. Ultra-sensitive sub-bandgap photocurrent spectroscopy reveals that the minimum photon energy for optical charge generation in OPDs correlates with the dark current thermal activation energy. The dark current in OPDs is attributed to thermal charge generation at the donor-acceptor interface mediated by intra-gap states near the band edges.

Towards User-Centred Prosthetics Research Beyond the Laboratory.

The purpose of this study was to explore a range of perspectives on how academic research and clinical assessment of upper-limb prosthetics could happen in environments outside of laboratories and clinics, such as within peoples' homes. Two co-creation workshops were held, which included people who use upper limb prosthetic devices (hereafter called users), clinicians, academics, a policy stakeholder, and a representative from the upper-limb prosthetics industry (hereafter called professionals). The discussions during the workshops indicate that research and clinical assessment conducted remotely from a laboratory or clinic could inform future solutions that address user needs. Users were open to the idea of sharing sensor and contextual data from within their homes to external laboratories during research studies. However, this was dependent upon several considerations, such as choice and control over data collection. Regarding clinical assessment, users had reservations of how data may be used to inform future prosthetic prescriptions whilst, clinicians were concerned with resource implications and capacity to process user data. The paper presents findings of the discussions shared by participants during both workshops. The paper concludes with a conjecture that collecting sensor and contextual data from users within their home environment will contribute towards literature within the field, and potentially inform future care policies for upper limb prosthetics. The involvement of users during such studies will be critical and can be enabled via a co-creation approach. In the short term, this may be achieved through academic research studies, which may in the long term inform a framework for clinical in-home trials and clinical remote assessment.

Multiscale nest-site selection of ducks in the western boreal forest of Alberta.

There is limited data regarding the nesting ecology of boreal ducks and their response to industrial development, despite this region being an important North American breeding area. We investigated how landcover and oil and gas development affect third-order nest-site selection of boreal ducks. We located duck nests in Alberta's western boreal forest between 2016 and 2018. We used multiscale analysis to identify how scale affects the selection of a resource using generalized linear mixed-effects models and determined what scale-optimized combination of landscape features were most important in describing where ducks nest. We located 136 nests of six species of upland nesting ducks between 2016 and 2018. The magnitude, direction, and best spatial scale varied by resource. For landcover, ducks selected nest-sites associated with mineral wetlands (300 m) and open water (300 m). Ducks avoided greater densities of seismic lines (300 m) and pipelines (2500 m) but selected nest-sites associated with borrow pits (300 m) and roads (1000 m). We used our models to predict important duck nesting habitat in the boreal forest, which can support conservation and management decisions. We recommend conservation actions target the conservation of mineral wetlands and associated habitats within this working landscape. Further research is necessary to understand the adaptive consequences of nest-site selection and how industrial development influences important nest predators.

Increasing Voluntary Myoelectric Training Time Through Game Design.

In virtual prosthetic training research, serious games have been investigated for over 30 years. However, few game design elements are used and assessed for their effect on the voluntary adherence and repetition of the performed task. We compared two game-based versions of an established myoelectric-controlled virtual prosthetic training task with an interface without game elements of the same task [for video, see (Garske, 2022)]. Twelve limb-intact participants were sorted into three groups of comparable ability and asked to perform the task as long as they were motivated. Following the task, they completed a questionnaire regarding their motivation and engagement in the task. The investigation established that participants in the game-based groups performed the task significantly longer when more game design elements were implemented in the task (medians of 6 vs. 9.5 vs. 14 blocks for groups with increasing number of different game design elements). The participants in the game-based versions were also more likely to end the task out of fatigue than for reasons of boredom or frustration, which was verified by a fatigue analysis of the myoelectric signal. We demonstrated that the utilization of game design methodically in virtual myoelectric training tasks can support adherence and duration of a virtual training, in the short-term. Whether such short-term enhanced engagement would lead to long-term adherence remains an open question.

Endometriosis expresses a molecular pattern consistent with decreased retinoid uptake, metabolism and action.

BACKGROUND: Retinoic acid (RA) regulates key biological processes, including differentiation, apoptosis and cell survival. RA mediates induction of 17 beta-hydroxysteroid dehydrogenase type 2 mRNA, catalyzing the conversion of estradiol to estrone, in endometrium but not endometriosis because of a defect in endometriotic stromal cells. This defect may involve both the uptake and metabolism of RA. In this study, we analyze the expression of genes involved in RA signaling in normal endometrium and endometriosis. METHODS: Tissue and stromal cells from ovarian endometriomas and eutopic endometrium from disease-free women were collected. Real-time reverse transcription-polymerase chain reaction was used to measure mRNA levels. Western blotting was used to evaluate protein expression. RESULTS: We found that endometriotic tissue and stromal cells demonstrated significantly decreased mRNA expression of the major genes involved in RA signaling, including STRA6, CRBP1, ALDH1A2, CRABP2 and FABP5. We found increased levels of CYP26B1, responsible for RA metabolism. Nuclear extracts showed that RARα, RXRα and PPARß/δ were underexpressed in both tissues and stromal cells from endometriotic tissue. Differences in protein levels were confirmed by western blotting. CONCLUSIONS: Endometriosis is characterized by a gene expression pattern suggesting a decrease in uptake and metabolism of RA. Because RA is integral in regulating key biological processes involved in cell survival, this alteration could partially explain the resistance to apoptosis found in endometriosis.

A Network-Enabled Myoelectric Platform for Prototyping Research Outside of the Lab.

We present a network-enabled myoelectric platform for performing research outside of the laboratory environment. A low-cost, flexible, modular design based on common Internet of Things connectivity technology allows home-based research to be piloted. An outline of the platform is presented followed by technical results obtained from ten days of home-based tests with three participants. Results show the system enabled collection of close to 12,000 trials during around 28 cumulative hours of use. Home-based testing of multiple participants in parallel offers efficiency gains and provides a intuitive route toward long-term testing of upper-limb prosthetic devices in more naturalistic settings.Clinical relevance- In-home myoelectric training reduces clinician time. Network-enabled systems with back-end dashboards allow clinicians to monitor patients myoelectric ability over time and will provide a new way of accessing information about how upper-limb prosthetics are commonly used.

Long-Term Myoelectric Training with Delayed Feedback in the Home Environment.

Myoelectric prosthesis users typically do not receive immediate feedback from their device. They must be able to consistently produce distinct muscle activations in the absence of augmented feedback. In previous experiments, abstract decoding has provided real-time visual feedback for closed loop control. It is unclear if the performance in those experiments was due to short-term adaptation or motor learning. To test if similar performance could be reached without short-term adaptation, we trained participants with a delayed feedback paradigm. Feedback was delayed until after the ~1.5 s trial was completed. Three participants trained for five days in their home environments, completing a cumulative total of 4920 trials. Participants became highly accurate while receiving no real-time feedback of their control input. They were also able to retain performance gains across days. This strongly suggests that abstract decoding with delayed feedback facilitates motor learning, enabling four class control without immediate feedback.