All optical neural interfaces.

Brain/computer interfaces (BCIs) rely on the concurrent recording of many channels of electrical activity from excitable tissue. Traditionally such neural interfacing has been performed using cumbersome, channel-limited multielectrode arrays. We believe that BCIs can greatly benefit from using an optical approach based on simple yet powerful liquid-crystal based transducer technology. This approach potentially offers a technology platform that can sustain the necessary bandwidth, density of channels, responsivity, and conformability that are required for the long-term viability of such interfaces. In this paper we review the overall architecture of this approach, the challenges it faces, and the solutions that are being developed at UNSW Sydney.

The stability of care preferences following acute illness: a mixed methods prospective cohort study of frail older people.

BACKGROUND: Patient preferences are integral to person-centred care, but preference stability is poorly understood in older people, who may experience fluctuant illness trajectories with episodes of acute illness. We aimed to describe, and explore influences on the stability of care preferences in frail older people following recent acute illness. METHODS: Mixed-methods prospective cohort study with dominant qualitative component, parallel data collection and six-month follow up. STUDY POPULATION: age ≥ 65, Rockwood Clinical Frailty score ≥ 5, recent acute illness requiring acute assessment/hospitalisation. Participants rated the importance of six preferences (to extend life, improve quality of life, remain independent, be comfortable, support 'those close to me', and stay out of hospital) at baseline, 12 and 24 weeks using a 0-4 scale, and ranked the most important. A maximum-variation sub-sample additionally contributed serial in-depth qualitative interviews. We described preference stability using frequencies and proportions, and undertook thematic analysis to explore influences on preference stability. RESULTS: 90/192 (45%) of potential participants consented. 82/90 (91%) answered the baseline questionnaire; median age 84, 63% female. Seventeen undertook qualitative interviews. Most participants consistently rated five of the six preferences as important (range 68-89%). 'Extend life' was rated important by fewer participants (32-43%). Importance ratings were stable in 61-86% of cases. The preference ranked most important was unstable in 82% of participants. Preference stability was supported by five influences: the presence of family support; both positive or negative care experiences; preferences being concordant with underlying values; where there was slowness of recovery from illness; and when preferences linked to long term goals. Preference change was related to changes in health awareness, or life events; if preferences were specific to a particular context, or multiple concurrent preferences existed, these were also more liable to change. CONCLUSIONS: Preferences were largely stable following acute illness. Stability was reinforced by care experiences and the presence of family support. Where preferences were unstable, this usually related to changing health awareness. Consideration of these influences during preference elicitation or advance care planning will support delivery of responsive care to meet preferences. Obtaining longer-term data across diverse ethnic groups is needed in future research.

How many people will need palliative care in 2040? Past trends, future projections and implications for services.

BACKGROUND: Current estimates suggest that approximately 75% of people approaching the end-of-life may benefit from palliative care. The growing numbers of older people and increasing prevalence of chronic illness in many countries mean that more people may benefit from palliative care in the future, but this has not been quantified. The present study aims to estimate future population palliative care need in two high-income countries. METHODS: We used mortality statistics for England and Wales from 2006 to 2014. Building on previous diagnosis-based approaches, we calculated age- and sex-specific proportions of deaths from defined chronic progressive illnesses to estimate the prevalence of palliative care need in the population. We calculated annual change over the 9-year period. Using explicit assumptions about change in disease prevalence over time, and official mortality forecasts, we modelled palliative care need up to 2040. We also undertook separate projections for dementia, cancer and organ failure. RESULTS: By 2040, annual deaths in England and Wales are projected to rise by 25.4% (from 501,424 in 2014 to 628,659). If age- and sex-specific proportions with palliative care needs remain the same as in 2014, the number of people requiring palliative care will grow by 25.0% (from 375,398 to 469,305 people/year). However, if the upward trend observed from 2006 to 2014 continues, the increase will be of 42.4% (161,842 more people/year, total 537,240). In addition, disease-specific projections show that dementia (increase from 59,199 to 219,409 deaths/year by 2040) and cancer (increase from 143,638 to 208,636 deaths by 2040) will be the main drivers of increased need. CONCLUSIONS: If recent mortality trends continue, 160,000 more people in England and Wales will need palliative care by 2040. Healthcare systems must now start to adapt to the age-related growth in deaths from chronic illness, by focusing on integration and boosting of palliative care across health and social care disciplines. Countries with similar demographic and disease changes will likely experience comparable rises in need.

Mapping of bionic array electric field focusing in plasmid DNA-based gene electrotransfer.

Molecular medicine through gene therapy is challenged to achieve targeted action. This is now possible utilizing bionic electrode arrays for focal delivery of naked (plasmid) DNA via gene electrotransfer. Here, we establish the properties of array-based electroporation affecting targeted gene delivery. An array with eight 300 µm platinum ring electrodes configured as a cochlear implant bionic interface was used to transduce HEK293 cell monolayers with a plasmid-DNA green fluorescent protein (GFP) reporter gene construct. Electroporation parameters were pulse intensity, number, duration, separation and electrode configuration. The latter determined the shape of the electric fields, which were mapped using a voltage probe. Electrode array-based electroporation was found to require ~100 × lower applied voltages for cell transduction than conventional electroporation. This was found to be due to compression of the field lines orthogonal to the array. A circular area of GFP-positive cells was created when the electrodes were ganged together as four adjacent anodes and four cathodes, whereas alternating electrode polarity created a linear area of GFP-positive cells. The refinement of gene delivery parameters was validated in vivo in the guinea pig cochlea. These findings have significant clinical ramifications, where spatiotemporal control of gene expression can be predicted by manipulation of the electric field via current steering at a cellular level.

Assessing fall risk using wearable sensors: a practical discussion. A review of the practicalities and challenges associated with the use of wearable sensors for quantification of fall risk in older people.

Identification of older people most at risk of falling may facilitate early preventative intervention to reduce the likelihood of falls occurring. While many clinical fall risk assessment techniques exist, they often require subjective assessor interpretation, or are not appropriate for unsupervised screening of larger populations owing to a number of issues including safety, ability to reliably perform the assessment, and requirements for unwieldy apparatus. Researchers have more recently attempted to address some of these deficits by instrumenting new or existing physical fall risk assessments with wearable motion sensors to make such assessments more objective, quicker to administer, and potentially more appropriate for deployment for unsupervised use in the community. The objective of this paper is to discuss various practical questions involving sensor-based fall risk assessment (SFRA). Many of the issues discussed contribute to answering the important question of whether SFRA should or can be used in either a supervised or an unsupervised manner, and what possible deployment scenarios exist for it.

What influenced people with chronic or refractory breathlessness and advanced disease to take part and remain in a drug trial? A qualitative study.

BACKGROUND: Recruitment and retention in clinical trials remains an important challenge, particularly in the context of advanced disease. It is important to understand what affects retention to improve trial quality, minimise attrition and reduce missing data. We conducted a qualitative study embedded within a randomised feasibility trial and explored what influenced people to take part and remain in the trial. METHODS: We conducted a qualitative study embedded within a double-blind randomised trial (BETTER-B[Feasibility]: BETter TreatmEnts for Refractory Breathlessness) designed using a person-centred approach. Participants with cancer, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), or chronic heart failure (CHF), with a modified Medical Research Council dyspnoea scale grade of 3/4 were recruited from three UK sites. A convenience subsample completed qualitative interviews after the trial. Interviews were analysed using thematic analysis. Results were considered in relation to the core elements of person-centred care and our model of the person-centred trial. RESULTS: In the feasibility trial 409 people were screened for eligibility, and 64 were randomised. No participant was lost to follow-up. Twenty-two participants took part in a qualitative interview. Eleven had a diagnosis of COPD, 8 ILD, 2 CHF and 1 lung cancer. The participants' median age was 71 years (range 56-84). Sixteen were male. Twenty had completed the trial, and two withdrew due to adverse effects. The relationship between patient and professional, potential for benefit, trial processes and the intervention all influenced the decision to participate in the trial. The relationship with the research team and continuity, perceived benefit, and aspects relating to trial processes and the intervention influenced the decision to remain in the trial. CONCLUSIONS: In this feasibility trial recruitment targets were met, attrition levels were low, and aspects of the person-centred approach were viewed positively by trial participants. Prioritisation of the relationship between the patient and professional; person-centred processes, including home visits, assistance with questionnaires, and involvement of the carer; and enabling people to participate by having processes in line with individual capabilities appear to support recruitment and retention in clinical trials in advanced disease. We recommend the integration of a person-centred approach in all clinical trials. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN32236160. Registered on 13 June 2016.

Non-invasive estimation of pulsatile flow and differential pressure in an implantable rotary blood pump for heart failure patients.

We propose dynamical models for pulsatile flow and head estimation in an implantable rotary blood pump. Pulsatile flow and head data were obtained using a circulatory mock loop where fluid solutions with different values of viscosities were used as a blood analogue with varying haematocrit (HCT). Noninvasive measurements of power and pump speed were used with HCT values as inputs to the flow model while the estimated flow was used with the speed as inputs to a head estimation model. Linear regression analysis between estimated and measured flows obtained from a mock loop resulted in a highly significant correlation (R2=0.982) and a mean absolute error (e) of 0.323 L min(-1), while for head, R2=0.933 and e=7.682 mmHg were obtained. R2=0.849 and e=0.584 L min(-1) were obtained when the same model derived in the mock loop was used for flow estimation in ex vivo porcine data (N=6). Furthermore, in the steady state, the solution of the presented flow model can be described by a previously designed and verified static model. The models developed herein will play a vital role in developing a robust control system of the pump flow coping with changing physiological demands.

Mirtazapine for chronic breathlessness? A review of mechanistic insights and therapeutic potential.

INTRODUCTION: Chronic breathlessness is a common and distressing symptom of advanced disease with few effective treatments. Central nervous system mechanisms are important in respiratory sensation and control. Consequently, drugs which may modify processing and perception of afferent information in the brain may have a role. Antidepressants have been proposed; however, current evidence is limited. Of potentially suitable antidepressants, mirtazapine is an attractive option given its tolerability profile, low cost, and wide availability, along with additional potential benefits. Areas covered: The paper provides an overview of the physiology of breathlessness, with an emphasis on central mechanisms, particularly the role of fear circuits and the associated neurotransmitters. It provides a potential rationale for how mirtazapine may improve chronic breathlessness and quality of life in patients with advanced disease. The evidence was identified by a literature search performed in PubMed through to October 2018. Expert opinion: Currently, there is insufficient evidence to support the routine use of antidepressants for chronic breathlessness in advanced disease. Mirtazapine is a promising candidate to pursue, with definitive randomized controlled trials required to determine its efficacy and safety in this setting.

Development and performance of a biomimetic artificial perilymph for in vitro testing of medical devices.

OBJECTIVE: Cochlear implants interface with the fluid in the cochlea called perilymph. The volume of this fluid present in human and animal model cochlea is prohibitively low for isolation for in vitro studies. Thus, there is a need for an artificial perilymph that reflects the complexity of this fluid in terms of competitive protein adsorption. APPROACH: This study established a biomimetic artificial perilymph (BAP) comprising serum albumin, immunoglobulin G, transferrin, inter-alpha-trypsin inhibitor, apolipoprotein A1 and complement C3 to represent the major components of human perilymph. Adsorption of the BAP components to platinum was analysed. MAIN RESULTS: It was established that this six component BAP provided competitive and complex adsorption behaviours consistent with biologically derived complex fluids. Additionally, adsorption of the BAP components to platinum cochlear electrodes resulted in a change in polarisation impedance consistent with that observed for the cochlear device in vivo. SIGNIFICANCE: This study established a BAP fluid suitable for furthering the understanding of the implant environment for electroactive devices that interface with the biological environment.

Image analysis for microelectronic retinal prosthesis.

By way of extracellular, stimulating electrodes, a microelectronic retinal prosthesis aims to render discrete, luminous spots-so-called phosphenes-in the visual field, thereby providing a phosphene image (PI) as a rudimentary remediation of profound blindness. As part thereof, a digital camera, or some other photosensitive array, captures frames, frames are analyzed, and phosphenes are actuated accordingly by way of modulated charge injections. Here, we present a method that allows the assessment of image analysis schemes for integration with a prosthetic device, that is, the means of converting the captured image (high resolution) to modulated charge injections (low resolution). We use the mutual-information function to quantify the amount of information conveyed to the PI observer (device implantee), while accounting for the statistics of visual stimuli. We demonstrate an effective scheme involving overlapping, Gaussian kernels, and discuss extensions of the method to account for shortterm visual memory in observers, and their perceptual errors of omission and commission.

From A to Z: Wearable technology explained.

Wearable technology (WT) has become a viable means to provide low-cost clinically sensitive data for more informed patient assessment. The benefit of WT seems obvious: small, worn discreetly in any environment, personalised data and possible integration into communication networks, facilitating remote monitoring. Yet, WT remains poorly understood and technology innovation often exceeds pragmatic clinical demand and use. Here, we provide an overview of the common challenges facing WT if it is to transition from novel gadget to an efficient, valid and reliable clinical tool for modern medicine. For simplicity, an A-Z guide is presented, focusing on key terms, aiming to provide a grounded and broad understanding of current WT developments in healthcare.

A quantitative analysis of head movement behaviour during visual acuity assessment under prosthetic vision simulation.

In most current vision prosthesis designs, head movement is the sole director of visual gaze and scanning due to the head-mounted nature of the camera. Study of this unnatural behaviour may provide insight into improved prosthesis designs and rehabilitation procedures. In this paper, we conducted a psychophysical study to investigate the characteristics of head movements of normally sighted subjects undergoing a visual acuity task in simulated prosthetic vision (SPV). In 12 naïve, untrained subjects, we recorded spontaneous changes in the amount of head movements during SPV sessions compared to control (normal vision) sessions. The observed behaviour continued to be refined until five or six sessions of practice. Increased head movement velocity was shown to be correlated to improved visual acuity performance, up to 0.3 logMAR, an equivalent of detecting details at half the physical size compared to complete deprivation of head movements. We postulate that visual scanning can as much as double the spatial frequency information in prosthetic vision. Increased head movement velocity observed when subjects were attempting smaller test items and for low-pass filtering schemes with higher cut-off frequencies may be further evidence that higher frequency content may be available through visual scanning, unconsciously driving subjects to increase head movement velocity.

Simulating auditory and visual sensorineural prostheses: a comparative review.

Microelectronic vision prosthesis proposes to render luminous spots (so-called phosphenes) in the visual field of the otherwise blind subject by way of an implanted array of stimulating electrodes, and in doing so restore some spatial vision. There are now many research teams worldwide working towards a therapeutic device, analogous to the cochlear implant, for the profoundly blind. Despite the similarities between the cochlear implant and vision prostheses, there are few instances in the literature where the two approaches are compared and contrasted with a mind to informing the science and engineering of the latter. This is the focus of the present review; specifically, our interest is psychophysics and signal processing. Firstly, we examine the cochlear implant, and review a handful of psychophysical work: the acoustic simulation of cochlear implants and the method used. We focus on the use of normally hearing subjects (played coloured noise bands or sine waves) as a means of investigating cochlear-implant efficacy and speech processing algorithms. These results provide guidance to vision researchers, for they address the interpretation of simulation data, and flag key areas, such as 'artificial' perception in the presence of noise, that require experimental work in coming years. Secondly, we provide an up-to-date review of the body of analogous psychophysical work: the visual simulation, involving normal observers, of microelectronic vision prosthesis. These simulations allow predictions as to the likely clinical efficacy of the prosthesis; indeed, results to date suggest that a number on the order of 100 implanted electrodes will afford subjects mobility and recognition of faces (and other complex stimuli), while even fewer electrodes facilitate reading printed text and very simple visuomanual tasks. Further, the simulations allow investigations of image and signal processing strategies, plus they provide researchers in the field, and other interested persons, a perceptual experience that approximates what a prosthesis will likely afford implantees.

A wideband frequency-shift keying demodulation technique for inductively powered biomedical implants.

A digital wideband frequency-shift keying (FSK) demodulator is presented. The primary application of this system is for inductively powered biomedical implants. By providing both the data and the power to the implant via an inductive link, the need for a battery and the interconnect wires are eliminated. This reduces revision surgeries that may take place for maintenance purposes, provides extra safety measures in the case of failures and reduces the risk of infection. However these devices are challenged by power requirements and size availability at the receiving site and often require a high data rate. These challenges lead to the need for an efficient demodulation technique, as traditional methods often do not overcome the restrictions that prevail. The demodulator circuitry presented relies solely on delaying elements, utilising a delayed FSK carrier to sample the incoming FSK waveform. The system architecture is based on a digital environment and both the data and a synchronised clock are derived concurrently. This can be achieved with the coherent-FSK modulated raw binary data stream without the need of any additional baseband coding schemes. The demodulator circuitry was simulated up to a data rate of 5 Mbps while receiving a 5/10 MHz FSK carrier. The system was also implemented on the bench and experimentally tested at a data rate of 1.042 Mbps with no detectable bit error rate while receiving a 4.16/6.25 MHz FSK carrier signal.

Bank note recognition for the vision impaired.

Blind Australians find great difficulty in recognising bank notes. Each note has the same feel, with no Braille markings, irregular edges or other tangible features. In Australia, there is only one device available that can assist blind people recognise their notes. Internationally, there are devices available; however they are expensive, complex and have not been developed to cater for Australian currency. This paper discusses a new device, the MoneyTalker that takes advantage of the largely different colours and patterns on each Australian bank note and recognises the notes electronically, using the reflection and transmission properties of light. Different coloured lights are transmitted through the inserted note and the corresponding sensors detect distinct ranges of values depending on the colour of the note. Various classification algorithms were studied and the final algorithm was chosen based on accuracy and speed of recognition. The MoneyTalker has shown an accuracy of more than 99%. A blind subject has tested the device and believes that it is usable, compact and affordable. Based on the devices that are available currently in Australia, the MoneyTalker is an effective alternative in terms of accuracy and usability.

Unintended Consequences of Wearable Sensor Use in Healthcare. Contribution of the IMIA Wearable Sensors in Healthcare WG.

OBJECTIVES: As wearable sensors take the consumer market by storm, and medical device manufacturers move to make their devices wireless and appropriate for ambulatory use, this revolution brings with it some unintended consequences, which we aim to discuss in this paper. METHODS: We discuss some important unintended consequences, both beneficial and unwanted, which relate to: modifications of behavior; creation and use of big data sets; new security vulnerabilities; and unforeseen challenges faced by regulatory authorities, struggling to keep pace with recent innovations. Where possible, we proposed potential solutions to unwanted consequences. RESULTS: Intelligent and inclusive design processes may mitigate unintended modifications in behavior. For big data, legislating access to and use of these data will be a legal and political challenge in the years ahead, as we trade the health benefits of wearable sensors against the risk to our privacy. The wireless and personal nature of wearable sensors also exposes them to a number of unique security vulnerabilities. Regulation plays an important role in managing these security risks, but also has the dual responsibility of ensuring that wearable devices are fit for purpose. However, the burden of validating the function and security of medical devices is becoming infeasible for regulators, given the many software apps and wearable sensors entering the market each year, which are only a subset of an even larger 'internet of things'. CONCLUSION: Wearable sensors may serve to improve wellbeing, but we must be vigilant against the occurrence of unintended consequences. With collaboration between device manufacturers, regulators, and end-users, we balance the risk of unintended consequences occurring against the incredible benefit that wearable sensors promise to bring to the world.

Health-Enabling and Ambient Assistive Technologies: Past, Present, Future.

BACKGROUND: During the last decades, health-enabling and ambient assistive technologies became of considerable relevance for new informatics-based forms of diagnosis, prevention, and therapy. OBJECTIVES: To describe the state of the art of health-enabling and ambient assistive technologies in 1992 and today, and its evolution over the last 25 years as well as to project where the field is expected to be in the next 25 years. In the context of this review, we define health-enabling and ambient assistive technologies as ambiently used sensor-based information and communication technologies, aiming at contributing to a person's health and health care as well as to her or his quality of life. METHODS: Systematic review of all original articles with research focus in all volumes of the IMIA Yearbook of Medical Informatics. Surveying authors independently on key projects and visions as well as on their lessons learned in the context of health-enabling and ambient assistive technologies and summarizing their answers. Surveying authors independently on their expectations for the future and summarizing their answers. RESULTS: IMIA Yearbook papers containing statements on health-enabling and ambient assistive technologies appear first in 2002. These papers form a minor part of published research articles in medical informatics. However, during recent years the number of articles published has increased significantly. Key projects were identified. There was a clear progress on the use of technologies. However proof of diagnostic relevance and therapeutic efficacy remains still limited. Reforming health care processes and focussing more on patient needs are required. CONCLUSIONS: Health-enabling and ambient assistive technologies remain an important field for future health care and for interdisciplinary research. More and more publications assume that a person's home and their interaction therein, are becoming important components in health care provision, assessment, and management.

Numerical Simulation of a Biventricular Assist Device with Fixed Right Outflow Cannula Banding During Pulmonary Hypertension.

As a left ventricular assist device is designed to pump against the systemic vascular resistance (SVR), pulmonary congestion may occur when using such device for right ventricular support. The present study evaluates the efficacy of using a fixed right outflow banding in patients receiving biventricular assist device support under various circulatory conditions, including variations in the SVR, pulmonary vascular resistance (PVR), total blood volume (BV), as well as ventricular contractility. Effect of speed variation on the hemodynamics was also evaluated at varying degrees of PVR. Pulmonary congestion was observed at high SVR and BV. A reduction in right ventricular assist device (RVAD) speed was required to restore pulmonary pressures. Meanwhile, at a high PVR, the risk of ventricular suction was prevalent during systemic hypotension due to low SVR and BV. This could be compensated by increasing RVAD speed. Isolated right heart recovery may aggravate pulmonary congestion, as the failing left ventricle cannot accommodate the resultant increase in the right-sided flow. Compared to partial assistance, the sensitivity of the hemodynamics to changes in VAD speed increased during full assistance. In conclusion, our results demonstrated that the introduction of a banding graft with a 5 mm diameter guaranteed sufficient reserve of the pump speed spectrum for the regulation of acceptable hemodynamics over different clinical scenarios, except under critical conditions where drug administration or volume management is required.

Visual acuity measurement of prosthetic vision: a virtual-reality simulation study.

A virtual-reality simulation tested prosthetic visual acuity for both rectangular and hexagonal phosphene grids. Thirteen normally sighted, untrained subjects were required to identify the Landolt C optotype over ten sessions. Overall performance, performance by filter setting (image analysis), and performance by size and orientation of the Landolt C optotype are reported. The results indicated that the hexagonal grid had a slight (4.1%) but statistically significant (p < 0.0001) performance advantage over the rectangular grid for correct identification of the testing symbol. It was also observed that both the phosphene grids had distinct performance profiles relating to their respective spatial orientation. Over the course of the ten sessions, learning afforded subjects an averaged improved performance of 10%.

Reliability of cardiorespiratory measurements with a new ergospirometer during intense treadmill exercise in Thoroughbred horses.

This study investigated the reliability of measurements with a new equine ergospirometer (Quadflow). Heart rate and blood lactate responses during exercise in horses wearing the Quadflow and an open flow mask were also compared. The mean percentage error of the oxygen uptake measurements was 8.2% (range 2.1-12.5%). Percent error for peak expiratory flow rates ranged from 6.1% to 9.4 %, and for minute ventilation from 2.5% to 7.4%. The coefficients of variation of the means of four measurements in two horses exercising continuously at 9.0 m/s were <5% for variables related to pulmonary ventilation, and was 7.7% for oxygen uptake. The Quadflow mask resulted in small increases in blood lactate concentration and relative heart rate during submaximal exercise. It was concluded that between- and within-test reliability statistics for important measurements in equine clinical exercise testing were acceptable for routine use in a veterinary practice or research laboratory.