Digitizing tools for post introduction evaluation of rotavirus vaccine introduction in India.

Background and aims: The Rotavirus vaccine (RVV) introduction is a landmark event in the history of Indian public health as for the first time a novel, low-cost indigenous vaccine was introduced in a short timeline between 2016 and 2019. As per WHO mandate, post-introduction evaluation (PIE) be conducted within 6 to 12 months of vaccine introduction to provide an understanding of the operational aspects of the program. For RVV PIE, an innovative approach to developing and deploying a digitized tool was employed. The present study aims to document the processes followed for digitizing the data collection and analysis tools. Methods: The development of the RVV-PIE digital tool was undertaken in two phases. In the first phase, conceptualization and iteration of the modified WHO PIE tool were undertaken. Questions were organized sequentially to ensure natural progression in responses. The finalized questionnaire was converted to a digital version and extensive dummy data was entered to improve automated qualitative data analysis. Phase 2 involved updating the draft tool and incorporating changes to provide a field-tested version for deployment. Results: The digital version of the tool was successfully developed. The GPS functionality of the tool allowed live tracking of data collection making the process more accountable. The tool was prepopulated with reference materials and data points for easy reference and retrieval by the evaluators. The digitization of the tool also allowed easy visualization of data through maps, charts, and graphs on a real-time user-friendly dashboard. Conclusions: The digitization of the PIE tool for RVV in India has been a great learning experience where the dire situation of an ongoing pandemic catapulted us towards a more efficient and comprehensive process innovation. The RVV PIE tool could serve as a customizable digital PIE tool for other health programs heralding an era of a more effective and proficient process of PIE.

Enablers and barriers to rotavirus vaccine coverage in Assam, India- A qualitative study.

Background: Estimates suggest that 78,000 children died due to rotavirus gastroenteritis annually between 2011 and 2013 in India. The north eastern state of Assam reported 38.4% pediatric diarrheal admissions testing positive for rotavirus. Rotavirus vaccine (RVV) was introduced in Assam in 2017 following which the National Family Health Survey-5 (NFHS-5) (2019) revealed low RVV coverage in Assam with wide variation between the districts. the current study was conceptualized and undertaken to capture the enablers and barriers to RVV coverage in Assam. Methods: Qualitative study conducted in 5 randomly selected districts in Assam. Participants (key informants) were recruited by purposive sampling at each level of the health system including healthcare officials, service providers and caregivers based on availability. Thirty-five in-depth interviews (IDIs) and five focus group discussions (FGDs) were conducted. Interviews were tape recorded and transcribed. Data was coded and analyzed using the thematic framework approach. Results: Findings from the qualitative data collection were collated and analyzed under 7 identified themes. Difficult terrain, limited service provider availability and no catch-up training for new recruits were some of the barriers to RVV coverage. In contrast, Information, Education & Communication (IEC) in vernacular language, RVV safety profile, development partner support and adequate RVV supply were identified as some of the enablers of RVV coverage. Conclusion: Few broad recommendations to overcome identified barriers include comprehensive inter-sectoral coordination, regular monitoring and frequent refresher training sessions. There is a need for a future study utilizing existing coverage data and larger sample size to triangulate the findings of this study.

Oligourea helix bundle binds detergents with diverse polar head groups.

Here we report a series of crystal structures (and accompanying biophysical data) of an array of diverse detergent guests bound to an oligourea foldamer helix bundle. These results significantly increase our structural and chemical understanding of aqueous guest recognition by oligourea foldamers and will aid the design of further functionalised oligourea-based self-assemblies.

Benefits of thermal and distance-filtered imaging for wayfinding with prosthetic vision.

Visual prostheses such as the Argus II provide partial vision for individuals with limited or no light perception. However, their effectiveness in daily life situations is limited by scene complexity and variability. We investigated whether additional image processing techniques could improve mobility performance in everyday indoor environments. A mobile system connected to the Argus II provided thermal or distance-filtered video stimulation. Four participants used the thermal camera to locate a person and the distance filter to navigate a hallway with obstacles. The thermal camera allowed for finding a target person in 99% of trials, while unfiltered video led to confusion with other objects and a success rate of only 55% ([Formula: see text]). Similarly, the distance filter enabled participants to detect and avoid 88% of obstacles by removing background clutter, whereas unfiltered video resulted in a detection rate of only 10% ([Formula: see text]). For any given elapsed time, the success rate with filtered video was higher than with unfiltered video. After 90 s, participants' success rate reached above 50% with filtered video and 24% and 3% with normal camera in the first and second tasks, respectively. Despite individual variations, all participants showed significant improvement when using the thermal and distance filters compared to unfiltered video. Adding a thermal and distance filter to a visual prosthesis system can enhance the performance of mobility activities by removing clutter in the background, showing people and warm objects with the thermal camera, or nearby obstacles with the distance filter.

Diagnostic accuracy of RBC scintigraphy and CTA for detection of patients with suspected lower gastrointestinal bleeding: a systematic review and meta-analysis.

OBJECTIVE: Detection of lower gastrointestinal bleeding (LGIB) through noninvasive modalities is very important in the successful management of LGIB. RBC scintigraphy and CT have a role in the detection of LGIB and guiding the management of patient by localization of the bleeding site. However, only a small number of studies have evaluated the role of RBC scintigraphy and CT in the diagnosis of LGIB. This systematic review was conducted to evaluate the diagnostic performance of RBC scintigraphy and CT in the detection of LGIB in patients with clinical or biochemical findings suspicious of LGIB. METHODS: This systematic review followed PRISMA guidelines. Searches in PubMed, Scopus, and Embase were conducted using relevant keywords, and articles published through 30 April 2022, were included. Using endoscopy or surgical outcomes as the reference standard, the numbers of true and false positives and true and false negatives were extracted. Pooled estimates of diagnostic test accuracy - including sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and summary ROC (SROC) curve - were generated using bivariate random-effects meta-analysis. RESULTS: Three studies comprising 171 patients were included in the systematic review and meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for the detection of LGIB using RBC scintigraphy were 0.787 (95% CI, 0.643-0.893), 0.289 (95% CI, 0.164-0.443), 1.214 (95% CI, 0.923-1.597) and 0.576 (95% CI, 0.296-1.121) respectively. The area under the SROC curve was 0.73. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for the detection of LGIB using CT were 0.931 (95% CI, 0.772-0.992), 0.870 (95% CI, 0.737-0.951), 6.085 (95% CI, 0.840-44.097), 0.126 (95% CI, 0.006-2.509) respectively. The area under the SROC curve was 0.095. CONCLUSION: RBC scintigraphy has overall good sensitivity and CTA has excellent sensitivity specificity, positive and negative likelihood ratio in the detection of LGIB in patients with clinical or biochemical findings suspicious for LGIB.CTA along with RBC scintigraphy can be used algorithmically to rule out patients who do not have a localization for the site of LGIB thereby helping these patients to avoid invasive procedures like endoscopy or surgical explorations.

Using new cold chain technologies to extend the vaccine cold chain in India: Equipment performance, acceptability, systems fit, and costs.

This study evaluated the performance, acceptability, costs, and systems fit of three new cold chain devices in India: a second-generation ice-lined refrigerator (ILR), a solar direct drive (SDD) refrigerator, and a long-term passive device (LTPD). The evaluation was conducted over 15 months during 2016-2017. Sites were selected for their diversity in climate, terrain, and grid electrical supply, and 31 cold chain devices were deployed, 1 to each site. Results showed that all three technologies maintained correct temperatures. The SDD refrigerators had no malfunctions, whilst the ILRs had at least one malfunction, mostly due to the printed circuit board's sensitivity to the erratic power supply. The LTPD temperature display panel caused challenges initially that required replacement of all solar panels with lithium batteries. Yet the devices' long holdovers helped ensure vaccine potency. One challenge, particularly with the ILRs and SDD refrigerators, was condensation. The passively cooled LTPD was valued in settings with smaller populations and unreliable or no power; however, some its features, including the need to condition ice blocks, made it challenging to operate. In addition, the acceptable temperature range for the LTPD, as for all passively cooled devices (greater than 0 °C and less than + 10 °C), was confusing for some health workers due to the decades-long emphasis on maintaining temperatures at + 2 °C to + 8 °C. The greatest system-related benefit was establishment of new cold chain points (CCPs) at locations with intermittent or no grid electricity, bringing immunisation services closer to hard-to-reach areas. A key limitation of all three devices was the inability to freeze ice packs, which are required for vaccine carriers, somewhat restricting the potential of these technologies to reach underserved populations. Moreover, establishing new CCPs added costs to the health system. Results from this study, including costing data, can help guide decision-making.

Enablers and Barriers to the Scaling Up of Pneumococcal Conjugate Vaccine in India During the COVID-19 Pandemic: A Qualitative Study.

Background: Pneumonia is one of the leading causes of death in under-5 children in India. This led the Ministry of Health & Family Welfare (MoHFW) in India to decide for the nationwide roll-out of the Pneumococcal Conjugate Vaccine (PCV). However, the introduction of PCV became more complex in the face of unprecedented challenges set forth by the COVID-19 pandemic. The study aims to assess enablers and barriers to the introduction of PCV in India during the pandemic. Methodology: Qualitative research approach involving key-informant interviews from John Snow India (JSI), the lead technical agency that supported MoHFW in the PCV expansion was employed to delineate the enablers and barriers. Principle of saturation was employed to derive the sample size. Thematic analysis using inductive approach was based on the modified World Health Organization (WHO) framework for new vaccine introduction impact on the Immunization and Health Systems, using NVIVO 12 qualitative data analysis software. Results: A total of 11 key informants (4 national-level program managers and 7 state technical officers) were telephonically interviewed. The study found social acceptance, lower cost of the vaccine, and intensive communication activities as potential enablers. Other enablers for PCV introduction included a robust vaccine supply-chain system, ample cold-chain space availability, and strong political commitment, despite the ongoing second wave. Further, the identified barriers included poor physical access, insufficient social mobilization, and limited advocacy along with a stretched workforce. Conclusion: The study delineated several enablers and barriers to introducing PCV in the country during the pandemic. The existing barriers in the PCV roll-out prompted the need to address these gaps, making key program-based recommendations to improve future new vaccine introductions during the pandemic.

An exploratory simulation study and prediction model on human brain behavior and activity using an integration of deep neural network and biosensor Rabi antenna.

The plasmonic antenna probe is constructed using a silver rod embedded in a modified Mach-Zehnder interferometer (MZI) ad-drop filter. Rabi antennas are formed when space-time control reaches two levels of system oscillation and can be used as human brain sensor probes. Photonic neural networks are designed using brain-Rabi antenna communication, and transmissions are connected via neurons. Communication signals are carried by electron spin (up and down) and adjustable Rabi frequency. Hidden variables and deep brain signals can be obtained by external detection. A Rabi antenna has been developed by simulation using computer simulation technology (CST) software. Additionally, a communication device has been developed that uses the Optiwave program with Finite-Difference Time-Domain (OptiFDTD). The output signal is plotted using the MATLAB program with the parameters of the OptiFDTD simulation results. The proposed antenna oscillates in the frequency range of 192 THz to 202 THz with a maximum gain of 22.4 dBi. The sensitivity of the sensor is calculated along with the result of electron spin and applied to form a human brain connection. Moreover, intelligent machine learning algorithms are proposed to identify high-quality transmissions and predict the behavior of transmissions in the near future. During the process, a root mean square error (RMSE) of 2.3332(±0.2338) was obtained. Finally, it can be said that our proposed model can efficiently predict human mind, thoughts, behavior as well as action/reaction, which can be greatly helpful in the diagnosis of various neuro-degenerative/psychological diseases (such as Alzheimer's, dementia, etc.) and for security purposes.

Critical factors in the successful expansion of Pneumococcal Conjugate Vaccine in India during the COVID-19 pandemic.

India had decided to roll out PCV in India in 2015, but successful implementation of any new vaccine introduction mandates an enormous effort. PCV was scaled up during the COVID-19 pandemic, which posed new, unprecedented challenges in the vaccine rollout. However, India successfully expanded PCV in the country in record time across all states and Union Territories. During the pandemic, supply-side restrictions, delayed vaccine shipments, staff shortages, and restrictions in conducting training negatively affected the roll-out of PCV across the country. However, despite the ongoing pandemic, India successfully rolled out PCV across the country in 7 months. In this review, the authors have conducted a narrative review to delineate the crucial factors that helped in the successful expansion of PCV.

Distilling Nonlocality in Quantum Correlations.

Nonlocality, as established by the seminal Bell's theorem, is considered to be the most striking feature of correlations present in spacelike separated events. Its practical application in device independent protocols, such as secure key distribution, randomness certification, etc., demands identification and amplification of such correlations observed in the quantum world. In this Letter we study the prospect of nonlocality distillation, wherein, by applying a natural set of free operations (called wirings) on many copies of weakly nonlocal systems, one aims to generate correlations of higher nonlocal strength. In the simplest Bell scenario, we identify a protocol, namely, logical OR-AND wiring, that can distill nonlocality to a significantly high degree starting from arbitrarily weak quantum nonlocal correlations. As it turns out, our protocol has several interesting facets: (i) it demonstrates that a set of distillable quantum correlations has nonzero measure in the full eight-dimensional correlation space, (ii) it can distill quantum Hardy correlations by preserving its structure, (iii) it shows that (nonlocal) quantum correlations sufficiently close to the local deterministic points can be distilled by a significant amount. Finally, we also demonstrate efficacy of the considered distillation protocol in detecting postquantum correlations.

Development of a Choice-framework for Covid vaccines in India using a multi-criteria decision analysis approach.

BACKGROUND: Vaccines were crucial in controlling the Covid-19 pandemic. As more vaccines receive regulatory approval, stakeholders will be faced with several options and must make an appropriate choice for themselves. We proposed a multi-criteria decision analysis (MCDA) framework to guide decision-makers in comparing vaccines for the Indian context. METHODS: We adhered to the ISPOR guidance for the MCDA process. Seven vaccine options were compared under ten criteria. Through three virtual workshops, we obtained opinions and weights from citizens, private-sector hospitals, and public health organisations. Available evidence was rescaled and incorporated into the performance matrix. The final score for each vaccine was calculated for the different groups. We performed different sensitivity analyses to assess the consistency of the rank list. RESULTS: The cost, efficacy and operational score of the vaccines had the highest weights among the stakeholders. From the six scenario groups, Janssen had the highest score in four. This was driven by the advantage of having a single dose of vaccination. In the probabilistic sensitivity analysis for the overall group, Covaxin, Janssen, and Sputnik were the first three options. The participants expressed that availability, WHO approvals and safety, among others, would be crucial when considering vaccines. CONCLUSIONS: The MCDA process has not been capitalised on in healthcare decision-making in India and LMICs. Considering the available data and stakeholder preference at the time of the study, Covaxin, Janssen, and Sputnik were preferred options. The choice framework with the dynamic performance matrix is a valuable tool that could be adapted to different population groups and extended based on increasing vaccine options and emerging evidence. *ISPOR - The Professional Society for Health Economics and Outcomes Research.

Wrapper-based deep feature optimization for activity recognition in the wearable sensor networks of healthcare systems.

The Human Activity Recognition (HAR) problem leverages pattern recognition to classify physical human activities as they are captured by several sensor modalities. Remote monitoring of an individual's activities has gained importance due to the reduction in travel and physical activities during the pandemic. Research on HAR enables one person to either remotely monitor or recognize another person's activity via the ubiquitous mobile device or by using sensor-based Internet of Things (IoT). Our proposed work focuses on the accurate classification of daily human activities from both accelerometer and gyroscope sensor data after converting into spectrogram images. The feature extraction process follows by leveraging the pre-trained weights of two popular and efficient transfer learning convolutional neural network models. Finally, a wrapper-based feature selection method has been employed for selecting the optimal feature subset that both reduces the training time and improves the final classification performance. The proposed HAR model has been tested on the three benchmark datasets namely, HARTH, KU-HAR and HuGaDB and has achieved 88.89%, 97.97% and 93.82% respectively on these datasets. It is to be noted that the proposed HAR model achieves an improvement of about 21%, 20% and 6% in the overall classification accuracies while utilizing only 52%, 45% and 60% of the original feature set for HuGaDB, KU-HAR and HARTH datasets respectively. This proves the effectiveness of our proposed wrapper-based feature selection HAR methodology.

Adaptive Binding of Alkyl Glycosides by Nonpeptidic Helix Bundles in Water: Toward Artificial Glycolipid Binding Proteins.

Amphipathic water-soluble helices formed from synthetic peptides or foldamers are promising building blocks for the creation of self-assembled architectures with non-natural shapes and functions. While rationally designed artificial quaternary structures such as helix bundles have been shown to contain preformed cavities suitable for guest binding, there are no examples of adaptive binding of guest molecules by such assemblies in aqueous conditions. We have previously reported a foldamer 6-helix bundle that contains an internal nonpolar cavity able to bind primary alcohols as guest molecules. Here, we show that this 6-helix bundle can also interact with larger, more complex guests such as n-alkyl glycosides. X-ray diffraction analysis of co-crystals using a diverse set of guests together with solution and gas-phase studies reveals an adaptive binding mode whereby the apo form of the 6-helix bundle undergoes substantial conformational change to accommodate the hydrocarbon chain in a manner reminiscent of glycolipid transfer proteins in which the cavity forms upon lipid uptake. The dynamic nature of the self-assembling and molecular recognition processes reported here marks a step forward in the design of functional proteomimetic molecular assemblies.

Advances in hybrid peptide-based self-assembly systems and their applications.

Self-assembly of peptides demonstrates a great potential for designing highly ordered, finely tailored supramolecular arrangements enriched with high specificity, improved efficacy and biological activity. Along with natural peptides, hybrid peptide systems composed of natural and chemically diverse unnatural amino acids have been used in various fields, including drug delivery, wound healing, potent inhibition of diseases, and prevention of biomaterial related diseases to name a few. In this review, we provide a brief outline of various methods that have been utilized for obtaining fascinating structures that create an avenue to reproduce a range of functions resulting from these folds. An overview of different self-assembled structures as well as their applications will also be provided. We believe that this review is very relevant to the current scenario and will cover conformations of hybrid peptides and resulting self-assemblies from the late 20th century through 2022. This review aims to be a comprehensive and reliable account of the hybrid peptide-based self-assembly owing to its enormous influence in understanding and mimicking biological processes.

Eye movements and the perceived location of phosphenes generated by intracranial primary visual cortex stimulation in the blind.

BACKGROUND: Restoring sight for the blind using electrical stimulation of the visual pathways is feasible but demands an understanding of the spatial mapping of the visual world at the site of targeted stimulation, whether in the retina, thalamus, or cortex. While a visual cortex stimulator can bypass the eye and create visual percepts, there is an inherent dissociation between this stimulation and eye movements. It is unknown whether and how robustly the brain maintains the oculomotor circuitry in patients with bare- or no-light perception. OBJECTIVE: To critically and quantitatively evaluate the effect of eye movements have on phosphene locations elicited by cortical stimulation that bypasses the eyes in order to restore sight in blind subjects. METHODS: The NeuroPace Responsive Neurostimulator (RNS) and the Orion visual cortical prosthesis devices were used to electrically stimulate the visual cortex of blind subjects with bare or no light perception. Eye positions were recorded synchronized with stimulation and the location of the percepts were measured using a handheld marker. RESULTS: The locations of cortical stimulation-evoked percepts are shifted based on the eye position at the time of stimulation. Measured responses can be remapped based on measured eye positions to determine the retinotopic locations associated with the implanted electrodes, with remapped responses having variance limited by pointing error. CONCLUSIONS: Eye movements dominate the perceived location of cortical stimulation-evoked phosphenes, even after years of blindness. By accounting for eye positions, we can mimic retinal mapping as in natural sight.

Glow in the dark: Using a heat-sensitive camera for blind individuals with prosthetic vision.

To date, retinal implants are the only available treatment for blind individuals with retinal degenerations such as retinitis pigmentosa. Argus II is the only visual implant with FDA approval, with more than 300 users worldwide. Argus II stimulation is based on a grayscale image coming from a head-mounted visible-light camera. Normally, the 11°×19° field of view of the Argus II user is full of objects that may elicit similar phosphenes. The prosthesis cannot meaningfully convey so much visual information, and the percept is reduced to an ambiguous impression of light. This study is aimed at investigating the efficacy of simplifying the video input in real-time using a heat-sensitive camera. Data were acquired from four Argus II users in 5 stationary tasks with either hot objects or human targets as stimuli. All tasks were of m-alternative forced choice design where precisely one of the m≥2 response alternatives was defined to be "correct" by the experimenter. To compare performance with heat-sensitive and normal cameras across all tasks, regardless of m, we used an extension of signal detection theory to latent variables, estimating person ability and item difficulty in d' units. Results demonstrate that subject performance was significantly better across all tasks with the thermal camera compared to the regular Argus II camera. The future addition of thermal imaging to devices with very poor spatial resolution may have significant real-life benefits for orientation, personal safety, and social interactions, thereby improving quality of life.

Prosthetic Visual Performance Using a Disparity-Based Distance-Filtering System.

Purpose: At present, Argus II is the only retinal prosthesis approved by the US Food and Drug Administration that induces visual percepts in people who are blind from end-stage outer retinal degenerations such as retinitis pigmentosa. It has been shown to work well in sparse, high-contrast settings, but in daily practice visual performance with the device is likely to be hampered by the cognitive load presented by a cluttered real-world environment. In this study, we investigated the effect of a stereo-disparity-based distance-filtering system on four experienced Argus II users for a range of tasks: object localization, depth discrimination, orientation and size discrimination, and people detection and direction of motion. Methods: Functional vision was assessed in a semicontrolled setup using unfiltered (normal camera) and distance-filtered (stereo camera) imagery. All tasks were forced choice designs and an extension of signal detection theory to latent (unobservable) variables was used to analyze the data, allowing estimation of person ability (person measures) and task difficulty (item measures) on the same axis. Results: All subjects performed better with the distance filter compared with the unfiltered image (P  < 0.001 on all tasks except localization). Conclusions: Our results show that depth filtering using a disparity-based algorithm has significant benefits for people with Argus II implants. Translational Relevance: The improvement in functional vision with the distance filter found in this study may have an important impact on vision rehabilitation and quality of life for people with visual prostheses and ultra low vision.

The use of handheld marker to calibrate a field-programmable gate array based eye tracker for artificial vision system.

Tracking the eye of a blind patient can enhance the usability of an artificial vision system. In systems where the sensing element, i.e. the scene camera that captures the visual information, is mounted on the patient's head, the user must use head scanning in order to steer the line of sight of the implant to the region of interest. Integrating an eye tracker in the prosthesis will enable scanning using eye movements. The eye position will set the region of interest within the wide field-of-view of the scene camera. An essential requirement of an eye tracker is the need to calibrate it. Obviously, off-the-shelf calibration methods that require looking at known points in space cannot be used with blind users.Here we tested the feasibility of calibrating the eye-tracker based on pupil position and the location of the percept reported by the implant recipient, using a handheld marker. Pupil positions were extracted using custom image processing in a field-programmable-gate-array built into a glasses-mounted eye tracker. In the calibration process, electrodes were directly stimulated and the subject reported the location of the percept using a handheld marker. Linear regression was used to extract the transfer function from pupil position to gaze direction in the coordinates of the scene camera.In using the eye tracker with the proposed calibration method, patients demonstrated improved precision on a localization task with corresponding reduction of head movements.

Improved mobility performance with an artificial vision therapy system using a thermal sensor.

OBJECTIVE: To evaluate the benefit of integrating thermal imaging into an artificial vision therapy system, the Argus II retinal prosthesis, in simplifying a complex scene and improving mobility performance in the presence of other persons. APPROACH: Four Argus II retinal implant users were evaluated on two tasks: to locate and approach target persons in a booth, and to navigate a hallway while avoiding people. They completed the tasks using both the original Argus II system (the 'Argus II camera') and a thermal-integrated Argus II system (the 'thermal camera'). The safety and efficiency of their navigation were evaluated by their walking speed, navigation errors, and the number of collisions. MAIN RESULTS: Navigation performance was significantly superior when using the thermal camera compared to using the Argus II camera, including 75% smaller angle of deviation (p < 0.001), 48% smaller error of distance (p < 0.05), and 30% fewer collisions (p < 0.05). The thermal camera also brought the additional benefit of allowing the participants to perform the task in the dark as efficiently as in the light. More importantly, these benefits did not come at a cost of reduced walking speed. SIGNIFICANCE: Using the thermal camera in the Argus II system, compared to a visible-light camera, could improve the wearers' navigation performance by helping them better approach or avoid other persons. Adding the thermal camera to future artificial vision therapy systems may complement the visible-light camera and improve the users' mobility safety and efficiency, enhancing their quality of life.

The effect of waveform asymmetry on perception with epiretinal prostheses.

Objective: Retinal prosthetic implants have helped improve vision in patients blinded by photoreceptor degeneration. Retinal implant users report improvements in light perception and performing visual tasks, but their ability to perceive shapes and letters is limited due to the low precision of retinal activation, which is exacerbated by axonal stimulation and high perceptual thresholds. A previous in vitro study in our lab used calcium imaging to measure the spatial activity of mouse retinal ganglion cells (RGCs) in response to electrical stimulation. Based on this study, symmetric anodic-first (SA) stimulation effectively avoided axonal activation and asymmetric anodic-first stimulation (AA) with duration ratios (ratio of the anodic to cathodic phase) greater than 10 reduced RGC activation thresholds significantly. Applying these novel stimulation strategies in clinic may increase perception precision and improve the overall patient outcomes. Approach: We combined human subject testing and computational modeling to further examine the effect of SA and AA stimuli on perception shapes and thresholds for epiretinal stimulation of RGCs. Main results: Threshold measurement in three Argus II participants indicated that AA stimulation could increase perception probabilities compared to a standard symmetric cathodic-first (SC) pulse, and this effect can be intensified by addition of an interphae gap (IPG). Our in silico RGC model predicts lower thresholds with AA and asymmetric cathodic-first (AC) stimuli compared to a SC pulse. This effect was more pronounced at shorter pulse widths. The most effective pulse for threshold reduction with short pulse durations (≤0.12 ms) was AA stimulation with small duration ratios (≤5) and long IPGs (≥2 ms). For the 0.5 ms pulse duration, SC stimulation with IPGs longer than 0.5 ms, or asymmetric stimuli with large duration ratios (≥20) were most effective in threshold reduction. Phosphene shape analysis did not reveal a significant change in percept elongation with SA stimulation. However, there was a significant increase in percept size (P < 0.01) with AA stimulation compared to the standard pulse in one participant. Significane: Including asymmetric waveform capability will provide more flexible options for optimization and personalized fitting of retinal implants.