Deep learning for activity recognition in older people using a pocket-worn smartphone

Activity recognition can provide useful information about an older individual’s activity level and encourage older people to become more active to live longer in good health. This study aimed to develop an activity recognition algorithm for smartphone accelerometry data of older people. Deep learning algorithms, including convolutional neural network (CNN) and long short-term memory (LSTM), were evaluated in this study. Smartphone accelerometry data of free-living activities, performed by 53 older people (83.8 ± 3.8 years; 38 male) under standardized circumstances, were classified into lying, sitting, standing, transition, walking, walking upstairs, and walking downstairs. A 1D CNN, a multichannel CNN, a CNN-LSTM, and a multichannel CNN-LSTM model were tested. The models were compared on accuracy and computational efficiency. Results show that the multichannel CNN-LSTM model achieved the best classification results, with an 81.1% accuracy and an acceptable model and time complexity. Specifically, the accuracy was 67.0% for lying, 70.7% for sitting, 88.4% for standing, 78.2% for transitions, 88.7% for walking, 65.7% for walking downstairs, and 68.7% for walking upstairs. The findings indicated that the multichannel CNN-LSTM model was feasible for smartphone-based activity recognition in older people

The direct influence of retinal degeneration on electrical stimulation efficacy: Significant implications for retinal prostheses

Photoreceptor loss and inner retinal network remodeling severely impacts the ability of retinal prosthetic devices to create artificial vision. We developed a computational model of a degenerating retina based on rodent data and tested its response to retinal electrical stimulation. This model includes detailed network connectivity and diverse neural intrinsic properties, capable of exploring how the degenerated retina influences the performance of electrical stimulation during the degeneration process. Our model suggests the possibility of quantitatively modulating retinal ON and OFF pathways between phase II and III of retinal degeneration without requiring any differences between ON and OFF RGC intrinsic cellular properties. The model also provided insights about how remodeling events influence stage-dependent differential electrical responses of ON and OFF pathways.Clinical Relevance-This data-driven model can guide future development of retinal prostheses and stimulation strategies that may benefit patients at different stages of retinal disease progression, particularly in the early and mid-stages, thus increasing their global acceptance

Neural activity of retinal ganglion cells under continuous, dynamically-modulated high frequency electrical stimulation

Objective. Current retinal prosthetics are limited in their ability to precisely control firing patterns of functionally distinct retinal ganglion cell (RGC) types. The aim of this study was to characterise RGC responses to continuous, kilohertz-frequency-varying stimulation to assess its utility in controlling RGC activity. Approach. We used in vitro patch-clamp experiments to assess electrically-evoked ON and OFF RGC responses to frequency-varying pulse train sequences. In each sequence, the stimulation amplitude was kept constant while the stimulation frequency (0.5-10 kHz) was changed every 40 ms, in either a linearly increasing, linearly decreasing or randomised manner. The stimulation amplitude across sequences was increased from 10 to 300 µA. Main results. We found that continuous stimulation without rest periods caused complex and irreproducible stimulus-response relationships, primarily due to strong stimulus-induced response adaptation and influence of the preceding stimulus frequency on the response to a subsequent stimulus. In addition, ON and OFF populations showed different sensitivities to continuous, frequency-varying pulse trains, with OFF cells generally exhibiting more dependency on frequency changes within a sequence. Finally, the ability to maintain spiking behaviour to continuous stimulation in RGCs significantly reduced over longer stimulation durations irrespective of the frequency order. Significance. This study represents an important step in advancing and understanding the utility of continuous frequency modulation in controlling functionally distinct RGCs. Our results indicate that continuous, kHz-frequency-varying stimulation sequences provide very limited control of RGC firing patterns due to inter-dependency between adjacent frequencies and generally, different RGC types do not display different frequency preferences under such stimulation conditions. For future stimulation strategies using kHz frequencies, careful consideration must be given to design appropriate pauses in stimulation, stimulation frequency order and the length of continuous stimulation duration

Probing the Contribution of Vertical Processing Layers of the Retina to White-Noise Electrical Stimulation Responses

Optimal stimulus parameters for epiretinal prostheses have been investigated by analyzing retinal ganglion cell (RGC) spiking responses to white-noise electrical stimulation, through a spike-triggered average (STA) analysis technique. However, it is currently unknown as to activation of which retinal cells contribute to features of the STA. We conducted whole-cell patch clamping recordings in ON and OFF RGCs in response to white-noise epiretinal electrical stimulation by using different inhibitors of synaptic transmission in a healthy retina. An mGluR6 agonist, L-AP4, was firstly used to selectively block the output of photoreceptors (PRs) to ON bipolar cells (BCs). We subsequently fully blocked all synaptic inputs to RGCs using a combination of pharmacological agents. Our data shows that PRs dominate the ability of ON RGCs to integrate electrical pulses and form a unique STA shape, while BCs do not contribute in any way. In addition, our results demonstrate that the ability of OFF RGCs to integrate pulses is consistently impaired after blocking the PR to ON BC pathway. We hypothesise that the mechanisms underlying this co-effect are related to the narrow field AII amacrine cells connecting ON and OFF pathways.Clinical Relevance-Recent retinal studies recorded mirror-inverted STAs in ON and OFF retinal pathways, thus raising the possibility of designing a stimulation approach that can differentially activate ON and OFF pathways with electrical stimulation. However, the detailed contribution of three major retinal cell layers in forming characteristic STAs is still unclear. It is of great clinical relevance to investigate the isolated contribution of PRs to the electrically driven STA since PRs progressively degenerate in the course of retinal disease

Modulating functionally-distinct vagus nerve fibers using microelectrodes and kilohertz frequency electrical stimulation

Modulation of functionally distinct nerve fibers with bioelectronic devices provides a therapeutic opportunity for various diseases. In this study, we began by developing a computational model including four major subtypes of myelinated fibers and one unmyelinated fiber. Second, we used an intrafascicular electrode to perform kHz-frequency electric stimulation to preferentially modulate a population of fibers. Our model suggests that fiber physical properties and electrode-to-fascicle distance severely impacts stimulus-response relationships. Large diameter fibers (Aα-and Aβ-) were only minimally influenced by the fascicle size and electrode location, while smaller diameter fibers (Aδ-, B-and C-) indicated a stronger dependency.Clinical Relevance-Our findings support the possibility of selectively modulating functionally-distinct nerve fibers using electrical stimulation in a small, localized region. Our model provides an effective tool to design next-generation implantable devices and therapeutic stimulation strategies toward minimizing off-target effects

Neurotrophin gene augmentation by electrotransfer to improve cochlear implant hearing outcomes

This Review outlines the development of DNA-based therapeutics for treatment of hearing loss, and in particular, considers the potential to utilize the properties of recombinant neurotrophins to improve cochlear auditory (spiral ganglion) neuron survival and repair. This potential to reduce spiral ganglion neuron death and indeed re-grow the auditory nerve fibres has been the subject of considerable pre-clinical evaluation over decades with the view of improving the neural interface with cochlear implants. This provides the context for discussion about the development of a novel means of using cochlear implant electrode arrays for gene electrotransfer. Mesenchymal cells which line the cochlear perilymphatic compartment can be selectively transfected with (naked) plasmid DNA using array - based gene electrotransfer, termed ‘close-field electroporation’. This technology is able to drive expression of brain derived neurotrophic factor (BDNF) in the deafened guinea pig model, causing re-growth of the spiral ganglion peripheral neurites towards the mesenchymla cells, and hence into close proximity with cochlear implant electrodes within scala tympani. This was associated with functional enhancement of the cochlear implant neural interface (lower neural recruitment thresholds and expanded dynamic range, measured using electrically - evoked auditory brainstem responses). The basis for the efficiency of close-field electroporation arises from the compression of the electric field in proximity to the ganged cochlear implant electrodes. The regions close to the array with highest field strength corresponded closely to the distribution of bioreporter cells (adherent human embryonic kidney (HEK293)) expressing green fluorescent reporter protein (GFP) following gene electrotransfer. The optimization of the gene electrotransfer parameters using this cell-based model correlated closely with in vitro and in vivo cochlear gene delivery outcomes. The migration of the cochlear implant electrode array-based gene electrotransfer platform towards a clinical trial for neurotrophin-based enhancement of cochlear implants is supported by availability of a novel regulatory compliant mini-plasmid DNA backbone (pFAR4; plasmid Free of Antibiotic Resistance v.4) which could be used to package a ‘humanized’ neurotrophin expression cassette. A reporter cassette packaged into pFAR4 produced prominent GFP expression in the guinea pig basal turn perilymphatic scalae. More broadly, close-field gene electrotransfer may lend itself to a spectrum of potential DNA therapeutics applications benefitting from titratable, localised, delivery of naked DNA, for gene augmentation, targeted gene regulation, or gene substitution strategies

Home Telehealth Uptake and Continued Use Among Heart Failure and Chronic Obstructive Pulmonary Disease Patients: a Systematic Review

Background Home telehealth has the potential to benefit heart failure (HF) and chronic obstructive pulmonary disease (COPD) patients, however large-scale deployment is yet to be achieved. Purpose The aim of this review was to assess levels of uptake of home telehealth by patients with HF and COPD and the factors that determine whether patients do or do not accept and continue to use telehealth. Methods This research performs a narrative synthesis of the results from included studies. Results Thirty-seven studies met the inclusion criteria. Studies that reported rates of refusal and/or withdrawal found that almost one third of patients who were offered telehealth refused and one fifth of participants who did accept later abandoned telehealth. Seven barriers to, and nine facilitators of, home telehealth use were identified. Conclusions Research reports need to provide more details regarding telehealth refusal and abandonment, in order to understand the reasons why patients decide not to use telehealth

Assessment of carbon in woody plants and soil across a vineyard-woodland landscape

<p>Abstract</p> <p>Background</p> <p>Quantification of ecosystem services, such as carbon (C) storage, can demonstrate the benefits of managing for both production and habitat conservation in agricultural landscapes. In this study, we evaluated C stocks and woody plant diversity across vineyard blocks and adjoining woodland ecosystems (wildlands) for an organic vineyard in northern California. Carbon was measured in soil from 44 one m deep pits, and in aboveground woody biomass from 93 vegetation plots. These data were combined with physical landscape variables to model C stocks using a geographic information system and multivariate linear regression.</p> <p>Results</p> <p>Field data showed wildlands to be heterogeneous in both C stocks and woody tree diversity, reflecting the mosaic of several different vegetation types, and storing on average 36.8 Mg C/ha in aboveground woody biomass and 89.3 Mg C/ha in soil. Not surprisingly, vineyard blocks showed less variation in above- and belowground C, with an average of 3.0 and 84.1 Mg C/ha, respectively.</p> <p>Conclusions</p> <p>This research demonstrates that vineyards managed with practices that conserve some fraction of adjoining wildlands yield benefits for increasing overall C stocks and species and habitat diversity in integrated agricultural landscapes. For such complex landscapes, high resolution spatial modeling is challenging and requires accurate characterization of the landscape by vegetation type, physical structure, sufficient sampling, and allometric equations that relate tree species to each landscape. Geographic information systems and remote sensing techniques are useful for integrating the above variables into an analysis platform to estimate C stocks in these working landscapes, thereby helping land managers qualify for greenhouse gas mitigation credits. Carbon policy in California, however, shows a lack of focus on C stocks compared to emissions, and on agriculture compared to other sectors. Correcting these policy shortcomings could create incentives for ecosystem service provision, including C storage, as well as encourage better farm stewardship and habitat conservation.</p

Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions

Balancing repair and tolerance of DNA damage caused by alkylating agents

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity