A Multielectrode Nerve Cuff for Chronic Velocity Selective Recording in a sheep model.

Supra-sacral spinal cord injury (SCI) causes loss of bladder fullness sensation and bladder over-activity, leading to retention and incontinence respectively. Velocity selective recording (VSR) of nerve roots innervating the bladder might enable identification of bladder activity. A 10-electrode nerve cuff for sacral nerve root VSR was developed and tested in a sheep model during acute surgeries and chronic implantation for 6 months. The cuff performed well, with 5.90±1.90 kΩ electrode, and <~800 Ω tissue impedance after 189 days implantation with a stable device and tissues. This is important information for assessing the feasibility of chronic VSR.Clinical Relevance-This demonstrates the manufacturing and performance of a neural interface for chronic monitoring of bladder nerve afferents with applications in urinary incontinence and retention management following SCI.

Closed-loop optogenetic control of the dynamics of neural activity in non-human primates.

Electrical neurostimulation is effective in the treatment of neurological disorders, but associated recording artefacts generally limit its applications to open-loop stimuli. Real-time and continuous closed-loop control of brain activity can, however, be achieved by pairing concurrent electrical recordings and optogenetics. Here we show that closed-loop optogenetic stimulation with excitatory opsins enables the precise manipulation of neural dynamics in brain slices from transgenic mice and in anaesthetized non-human primates. The approach generates oscillations in quiescent tissue, enhances or suppresses endogenous patterns in active tissue and modulates seizure-like bursts elicited by the convulsant 4-aminopyridine. A nonlinear model of the phase-dependent effects of optical stimulation reproduced the modulation of cycles of local-field potentials associated with seizure oscillations, as evidenced by the systematic changes in the variability and entropy of the phase-space trajectories of seizures, which correlated with changes in their duration and intensity. We also show that closed-loop optogenetic neurostimulation could be delivered using intracortical optrodes incorporating light-emitting diodes. Closed-loop optogenetic approaches may be translatable to therapeutic applications in humans.

Silicone encapsulation of thin-film SiOx, SiOxNyand SiC for modern electronic medical implants: a comparative long-term ageing study.

Objective.Ensuring the longevity of implantable devices is critical for their clinical usefulness. This is commonly achieved by hermetically sealing the sensitive electronics in a water impermeable housing, however, this method limits miniaturisation. Alternatively, silicone encapsulation has demonstrated long-term protection of implanted thick-film electronic devices. However, much of the current conformal packaging research is focused on more rigid coatings, such as parylene, liquid crystal polymers and novel inorganic layers. Here, we consider the potential of silicone to protect implants using thin-film technology with features 33 times smaller than thick-film counterparts.Approach.Aluminium interdigitated comb structures under plasma-enhanced chemical vapour deposited passivation (SiOx, SiOxNy, SiOxNy+ SiC) were encapsulated in medical grade silicones, with a total of six passivation/silicone combinations. Samples were aged in phosphate-buffered saline at 67 ∘C for up to 694 days under a continuous ±5 V biphasic waveform. Periodic electrochemical impedance spectroscopy measurements monitored for leakage currents and degradation of the metal traces. Fourier-transform infrared spectroscopy, x-ray photoelectron spectroscopy, focused-ion-beam and scanning-electron- microscopy were employed to determine any encapsulation material changes.Main results.No silicone delamination, passivation dissolution, or metal corrosion was observed during ageing. Impedances greater than 100 GΩ were maintained between the aluminium tracks for silicone encapsulation over SiOxNyand SiC passivations. For these samples the only observed failure mode was open-circuit wire bonds. In contrast, progressive hydration of the SiOxcaused its resistance to decrease by an order of magnitude.Significance.These results demonstrate silicone encapsulation offers excellent protection to thin-film conducting tracks when combined with appropriate inorganic thin films. This conclusion corresponds to previous reliability studies of silicone encapsulation in aqueous environments, but with a larger sample size. Therefore, we believe silicone encapsulation to be a realistic means of providing long-term protection for the circuits of implanted electronic medical devices.

The Effects of the Presence of Multiple Conduction Velocities in the Analysis of Electrically-Evoked Compound Action Potentials (eCAPs).

New methods for the analysis of electrically-evoked compound action potentials (eCAPs) are described. Mammalian nerves tend to have broad multi-modal distributions of fibre diameters, which translates into a spread of conduction velocities. The method of velocity selective recording (VSR) is unable to distinguish between this spectral spread and the transfer function of the system. The concept of the velocity impulse function (VIF) is introduced as a tool to differentiate between these signal and system attributes. The new methods enable separate estimates of velocity spectral broadening and signal-to-noise ratio (SNR) to be obtained.

Selective Recording of Urinary Bladder Fullness from the Extradural Sacral Roots.

Managing the urinary bladder is of primary importance to clinicians and patients after trauma to the spinal cord. Sacral Anterior Root Stimulators that control the bladder have been available as clinical technology for many years, however these devices cannot measure the fullness of the urinary bladder or detect the onset of reflex voiding. In order to address this fundamental limitation, it is necessary to develop a method for recording the neural signals that encode bladder fullness. This paper presents a proof of concept technique for recording bladder afferents from the extradural sacral roots using a multiple electrode cuff. Results are provided from acute in-vivo experiments performed in sheep.

Infrared thermography and ulcer prevention in the high-risk diabetic foot: data from a single-blind multicentre controlled clinical trial.

AIM: To assess the usefulness of monthly thermography and standard foot care to reduce diabetic foot ulcer recurrence. METHODS: People with diabetes (n = 110), neuropathy and history of ≥ 1 foot ulcer participated in a single-blind multicentre clinical trial. Feet were imaged with a novel thermal imaging device (Diabetic Foot Ulcer Prevention System). Participants were randomized to intervention (active thermography + standard foot care) or control (blinded thermography + standard foot care) and were followed up monthly until ulcer recurrence or for 12 months. Foot thermograms of participants from the intervention group were assessed for hot spots (areas with temperature ≥ 2.2°C higher than the corresponding contralateral site) and acted upon as per local standards. RESULTS: After 12 months, 62% of participants were ulcer-free in the intervention group and 56% in the control group. The odds ratios of ulcer recurrence (intervention vs control) were 0.82 (95% CI 0.38, 1.8; P = 0.62) and 0.55 (95% CI 0.21, 1.4; P = 0.22) in univariate and multivariate logistic regression analyses, respectively. The hazard ratios for the time to ulcer recurrence (intervention vs control) were 0.84 (95% CI 0.45, 1.6; P = 0.58) and 0.67 (95% CI 0.34, 1.3; P = 0.24) in univariate and multivariate Cox regression analyses, respectively. CONCLUSIONS: Monthly intervention with thermal imaging did not result in a significant reduction in ulcer recurrence rate or increased ulcer-free survival in this cohort at high risk of foot ulcers. This trial has, however, informed the design of a refined study with longer follow-up and group stratification, further aiming to assess the efficacy of thermography to reduce ulcer recurrence.

Apparatus to investigate the insulation impedance and accelerated life-testing of neural interfaces.

OBJECTIVE: Neural interfaces and other implantable micro-devices that use polymer-encapsulated integrated circuits will only be allowed in medical devices when their lifetimes can be estimated from experimental data. An apparatus has been developed and tested that allows hundreds of insulated samples (interdigitated combs) to be aged under accelerated conditions of high temperature and voltage stress. Occasionally, aging is paused while the sample's impedance is measured; the impedance spectrogram may show degradation as it progresses before failure. APPROACH: The design was based on practical considerations which are reviewed. A Solartron Modulab provides the frequency response analyser and the femtoammeter. The apparatus can accommodate batches of samples at several temperatures and with different aging voltage waveforms. It is important to understand features of the spectra that are not due to comb-comb leakage, but come from other places (for example substrate-solution leakage); some have been observed and investigated using SPICE. MAIN RESULTS: The design is described in detail and test results show that it is capable of making measurements over long periods, at least up to 67 °C. Despite the size of the apparatus, background capacitance is about 1 pF and comb-comb capacitances of about 30 pF can be measured down to 10 mHz, an impedance of about 100 GΩ. An important discovery was the advantage of grounding the bathing solution, primarily in that it raises the measurement ceiling. Observation and SPICE simulation shows that leakage from the substrate to the bathing solution can give phase lags >90°, in contrast to comb-comb leakage which reduces phase lag to <90°. SIGNIFICANCE: The value of this paper is that it will facilitate research into the endurance of small implanted devices because, given a description of a proven apparatus, researchers can start building their own apparatus relatively quickly and with confidence.

The use of tungsten as a chronically implanted material.

This review paper shows that tungsten should not generally be used as a chronically implanted material. The metal has a long implant history, from neuroscience, vascular medicine, radiography, orthopaedics, prosthodontics, and various other fields, primarily as a result of its high density, radiopacity, tensile strength, and yield point. However, a crucial material criterion for chronically implanted metals is their long-term resistance to corrosion in body fluids, either by inherently noble metallic surfaces, or by protective passivation layers of metal oxide. The latter is often assumed for elemental tungsten, with references to its 'inertness' and 'stability' common in the literature. This review argues that in the body, metallic tungsten fails this criterion, and will eventually dissolve into the soluble hexavalent form W6+, typically represented by the orthotungstate [Formula: see text] (monomeric tungstate) anion. This paper outlines the metal's unfavourable corrosion thermodynamics in the human physiological environment, the chemical pathways to either metallic or metal oxide dissolution, the rate-limiting steps, and the corrosion-accelerating effects of reactive oxidising species that the immune system produces post-implantation. Multiple examples of implant corrosion have been reported, with failure by dissolution to varying extents up to total loss, with associated emission of tungstate ions and elevated blood serum levels measured. The possible toxicity of these corrosion products has also been explored. As the field of medical implants grows and designers explore novel solutions to medical implant problems, the authors recommend the use of alternative materials.

First demonstration of velocity selective recording from the pig vagus using a nerve cuff shows respiration afferents.

Neural interfaces have great potential to treat disease and disability by modulating the electrical signals within the nervous system. However, whilst neural stimulation is a well-established technique, current neural interfaces are limited by poor recording ability. Low signal amplitudes necessitate the use of highly invasive techniques that divide or penetrate the nerve, and as such are unsuitable for chronic implantation. In this paper, we present the first application of the velocity selective recording technique to the detection of respiration activity in the vagus nerve, which is involved with treatments for epilepsy, depression, and rheumatoid arthritis. Further, we show this using a chronically implantable interface that does not divide the nerve. We also validate our recording setup using electrical stimulation and we present an analysis of the recorded signal amplitudes. The recording interface was formed from a cuff containing ten electrodes implanted around the intact right vagus nerve of a Danish Landrace pig. Nine differential amplifiers were connected to adjacent electrodes, and the resulting signals were processed to discriminate neural activity based on conduction velocity. Despite the average single channel signal-to-noise ratio of - 5.8 dB, it was possible to observe distinct action potentials travelling in both directions along the nerve. Further, contrary to expectation given the low signal-to-noise ratio, we have shown that it was possible to identify afferent neural activity that encoded respiration. The significance of this is the demonstration of a chronically implantable method for neural recording, a result that will transform the capabilities of future neuroprostheses.

Assessment of carotid calcifications on digital panoramic radiographs: Retrospective analysis and review of the literature.

OBJECTIVES: To assess the validity of digital panoramic radiographs as an effective means of diagnosis for atherosclerosis and as a potential aid in the early detection of the disease. STUDY DESIGN: We reviewed 2014 digital panoramic radiographs taken throughout 2012 and 2013 to identify the presence of calcified atherosclerotic plaques of both female and male patients all aged over 18 years. In addition the medical records of these patients were reviewed in order to establish if there were any predisposing risk factors for atherosclerosis. Statistical analysis was performed to identify any possible link between radiographic atherosclerotic plaques and predisposing risk factors for atherosclerosis using univariate and multivariate models. Statistical significance criteria was defined as P<0.05. RESULTS: Out of 2014 patients (1149 female and 865 male), 191 (9.5%) were determined to have calcified atherosclerotic plaques on panoramic radiography. There was a statistically significant relationship between the presence of calcified atherosclerotic plaques and the established risk factors of atherosclerosis such as gender (OR=2.39, P<0.001), age (OR=1.5, P<0.001), stroke (OR=5.38, P<0.001) and hypertension (OR=2.11, P<0.001). CONCLUSION: To our knowledge this is the largest study investigating atherosclerotic plaques on digital panoramic radiographs ever carried out in Portugal. Dental practitioners need to be aware of these incidental findings and to consider referring these patients for further investigations to confirm diagnosis.

Lessons learned on recruitment and retention in hard-to-reach families in a phase III randomised controlled trial of preparatory information for children undergoing general anaesthesia.

BACKGROUND: Recruitment and retention are documented as two of the most difficult elements of conducting clinical trials. These issues are even more challenging in paediatric trials, particularly when the families being recruited and retained are deemed 'hard to reach'. METHODS: Through the authors' own reflection on the conduct of the trial this paper examines recruitment and retention with hard to reach families from the perspective of a recently completed clinical trial on preparatory information for children undergoing general anaesthesia for tooth extractions in which approximately 83% of those approached and eligible agreed to participate. RESULTS: The lessons learned for recruitment include: the importance of children's assent; maximising limited resources when screening and approaching potential participants; valuing families' time; and developing effective professional relationships. The retention rate was 83-85.5% at follow up time points up to 3.5 weeks following recruitment, insights into how this was accomplished include: ensuring continuity of care; determination to connect via telephone; valuing families' time; and close monitoring of appointment date changes. CONCLUSIONS: Implications for future paediatric trials with hard to reach families are discussed. TRIAL REGISTRATION: ISRCTN18265148 ; NIHR Portfolio 10,006. Date of Registration: 29 November 2013. The trial was registered after commencement but before completion of data collection.

A new method for spike extraction using velocity selective recording demonstrated with physiological ENG in Rat.

BACKGROUND: This paper describes a series of experiments designed to verify a new method of electroneurogram (ENG) recording that enables the rate of neural firing within prescribed bands of propagation velocity to be determined in real time. Velocity selective recording (VSR) has been proposed as a solution to the problem of increasing the information available from an implantable neural interface (typically with electrodes in circumferential nerve cuffs) and has been successful in transforming compound action potentials into the velocity domain. NEW METHOD: The new method extends VSR to naturally-evoked (physiological) ENG in which the rate of neural firing at particular velocities is required in addition to a knowledge of the velocities present in the recording. RESULTS: The experiments, carried out in rats required individual spikes to be distinct and non-overlapping, which could be achieved by a microchannel or small-bore cuff. In these experiments, strands of rat nerve were laid on ten hook electrodes in oil to demonstrate the principle. COMPARISON WITH EXISTING METHOD: The new method generates a detailed overview of the firing rates of neurons based on their conduction velocity and direction of propagation. In addition it allows real time working in contrast to existing spike sorting methods using statistical pattern processing techniques. CONCLUSIONS: Results show that by isolating neural activity based purely on conduction velocity it was possible to determine the onset of direct cutaneous stimulation of the L5 dermatome.

Composition of enamel pellicle from dental erosion patients.

Oral health is dependent upon a thin mobile film of saliva on soft and hard tissues. Salivary proteins adhere to teeth to form the acquired enamel pellicle which is believed to protect teeth from acid erosion. This study investigated whether patients suffering diet-induced dental erosion had altered enamel pellicles. Thirty patients suffering erosion were compared to healthy age-matched controls. Subjects wore a maxillary splint holding hydroxyapatite and human enamel blocks for 1 h. The acquired enamel pellicle was removed from the blocks and compared to the natural incisor pellicle. Basic Erosive Wear Examination scores confirmed that dental erosion was present in erosion patients and absent from healthy age-matched controls. Erosion patients had half the amount of proteins (BCA assay) within the acquired pellicle forming on splint blocks compared to normal controls (p < 0.05). In particular, statherin, a calcium-binding protein, was 35% less abundant (p < 0.05). Calcium concentration within the acquired pellicle was also reduced by 50% in erosion patients (p < 0.001). In contrast, the natural pellicle on the incisor had similar amounts of total protein in erosion patients and healthy controls. In summary, the formation of new acquired pellicles on surfaces was reduced in erosion patients, which may explain their greater susceptibility to acid erosion of teeth.

Motivation to study dental professions in one London Dental Institute.

INTRODUCTION: While past research has explored dental students' motivation to study, there is limited understanding in the reasons behind career choice for hygienists/therapists and dental nurses. The aim of this study was to investigate simultaneously the views of students of dentistry, hygiene/therapy and dental nursing in King's College London and explore similarities or differences in career choice. METHODS: All first-year students were invited to the questionnaire survey, exploring motivation to study using a 23-item instrument. Data were analysed using SPSS v18; statistical analysis included one-way analyses of variance and factor analysis. RESULTS: The overall response rate to the study was 75% (n = 209). Ten out of 23 factors were considered important by more than 80% of respondents, with 'job security' (93.8%), 'desire to work with people' (88%) and 'degree leading to recognised job' (87.5%) being top three. Analysis suggested that 52% of the total variation in motivating influences was explained by four factors: 'features of the job' (26%), 'education/skills' (11%), 'public service' (8%) and 'careers-advising' (7%); at group level 'features of the job' were significantly more important for the direct entrants to dentistry (P = 0.001). DISCUSSION: The findings suggest that across groups students were motivated to study by common influences reflecting altruistic, but also pragmatic and realistic motives, while 'features of the job' were more important for the direct entrants to dentistry.

Corrosion of silicon integrated circuits and lifetime predictions in implantable electronic devices.

Corrosion is a prime concern for active implantable devices. In this paper we review the principles underlying the concepts of hermetic packages and encapsulation, used to protect implanted electronics, some of which remain widely overlooked. We discuss how technological advances have created a need to update the way we evaluate the suitability of both protection methods. We demonstrate how lifetime predictability is lost for very small hermetic packages and introduce a single parameter to compare different packages, with an equation to calculate the minimum sensitivity required from a test method to guarantee a given lifetime. In the second part of this paper, we review the literature on the corrosion of encapsulated integrated circuits (ICs) and, following a new analysis of published data, we propose an equation for the pre-corrosion lifetime of implanted ICs, and discuss the influence of the temperature, relative humidity, encapsulation and field-strength. As any new protection will be tested under accelerated conditions, we demonstrate the sensitivity of acceleration factors to some inaccurately known parameters. These results are relevant for any application of electronics working in a moist environment. Our comparison of encapsulation and hermetic packages suggests that both concepts may be suitable for future implants.

Use of an implanted sacral nerve stimulator to restore urine voiding in chronically paraplegic dogs.

BACKGROUND: Loss of urinary control after spinal cord injury increases risk of urinary tract disease and is problematical for owners of affected dogs. OBJECTIVES: To design, implant, and test a sacral nerve stimulating device for controlling urine voiding in paraplegic dogs. ANIMALS: Nine pet dogs with severe thoracolumbar spinal cord injury causing paraplegia, loss of hindquarter sensation, and incontinence for more than 3 months. The procedure was offered prospectively to owners of suitable candidates after the irreversibility of the incontinence had been ascertained. METHODS: Open label clinical study. Surgically implantable electrode "books" were designed for insertion and retention of mixed sacral nerves. Sacral nerves were accessed via laminectomy and stimulated to test their ability to elicit detrusor contraction and then inserted into the electrode book, which was attached to a subcutaneously implanted, externally activated receiver. RESULTS: In 8/9 dogs, S2 nerves elicited the largest increases in intravesicular pressure with minimum stimulation and were placed in electrode books. Voiding efficiency was >90% in 8 of the 9 implanted dogs. No important detrimental effects of the procedure were observed. CONCLUSIONS AND CLINICAL IMPORTANCE: This sacral nerve stimulating implant is a simple and apparently effective neuroprosthetic device that restores urine voiding in paraplegic dogs.

Energetics of paraplegic cycling: adaptations to 12 months of high volume training.

PURPOSE: The efficiency of functional electrical-stimulation (FES) cycling in spinal cord injured and anaesthetised able-bodied cyclists has been found to be about one third of that reported during volitional cycling. The stimulation paradigm itself appears to be the main source of this inefficiency. It is unknown whether a period of high-volume training can induce adaptations that may influence the metabolic and electrical cost of FES cycling. METHOD: 11 individuals with paraplegia completed a 12-month, home-based, progressive FES cycle training programme (up to 5 × 60 min per wk). Stimulation cost, oxygen cost, efficiency and markers of anaerobic metabolism were determined before and after 6 and 12 months of training, during constant work-rate tests. RESULTS: Oxygen cost and efficiency did not significantly change after training. Total stimulation cost and blood lactate values reduced overall, while respiratory exchange ratios remained relatively high. CONCLUSIONS: The high metabolic cost of FES cycling is a result of non-physiological recruitment of predominantly fast muscle fibres. The electrical cost of cycling reduced by 37%, probably due to motor unit hypertrophy, and lactate oxidation capacity improved.

A quantitative release assessment for the noncommercial movement of companion animals: risk of rabies reintroduction to the United kingdom.

In 2004, the European Union (EU) implemented a pet movement policy (referred to here as the EUPMP) under EU regulation 998/2003. The United Kingdom (UK) was granted a temporary derogation from the policy until December 2011 and instead has in place its own Pet Movement Policy (Pet Travel Scheme (PETS)). A quantitative risk assessment (QRA) was developed to estimate the risk of rabies introduction to the UK under both schemes to quantify any change in the risk of rabies introduction should the UK harmonize with the EU policy. Assuming 100 % compliance with the regulations, moving to the EUPMP was predicted to increase the annual risk of rabies introduction to the UK by approximately 60-fold, from 7.79 × 10(-5) (5.90 × 10(-5), 1.06 × 10(-4)) under the current scheme to 4.79 × 10(-3) (4.05 × 10(-3), 5.65 × 10(-3)) under the EUPMP. This corresponds to a decrease from 13,272 (9,408, 16,940) to 211 (177, 247) years between rabies introductions. The risks associated with both the schemes were predicted to increase when less than 100 % compliance was assumed, with the current scheme of PETS and quarantine being shown to be particularly sensitive to noncompliance. The results of this risk assessment, along with other evidence, formed a scientific evidence base to inform policy decision with respect to companion animal movement.