Prediction Models Using Decision Tree and Logistic Regression Method for Predicting Hospital Revisits in Peritoneal Dialysis Patients.

Hospital revisits significantly contribute to financial burden. Therefore, developing strategies to reduce hospital revisits is crucial for alleviating the economic impacts. However, this critical issue among peritoneal dialysis (PD) patients has not been explored in previous research. This single-center retrospective study, conducted at Chang Gung Memorial Hospital, Chiayi branch, included 1373 PD patients who visited the emergency room (ER) between Jan 2002 and May 2018. The objective was to predict hospital revisits, categorized into 72-h ER revisits and 14-day readmissions. Of the 1373 patients, 880 patients visiting the ER without subsequent hospital admission were analyzed to predict 72-h ER revisits. The remaining 493 patients, who were admitted to the hospital, were studied to predict 14-day readmissions. Logistic regression and decision tree methods were employed as prediction models. For the 72-h ER revisit study, 880 PD patients had a revisit rate of 14%. Both logistic regression and decision tree models demonstrated a similar performance. Furthermore, the logistic regression model identified coronary heart disease as an important predictor. For 14-day readmissions, 493 PD patients had a readmission rate of 6.1%. The decision tree model outperformed the logistic model with an area under the curve value of 79.4%. Additionally, a high-risk group was identified with a 36.4% readmission rate, comprising individuals aged 41 to 47 years old with a low alanine transaminase level ≤15 units per liter. In conclusion, we present a study using regression and decision tree models to predict hospital revisits in PD patients, aiding physicians in clinical judgment and improving care.

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 usedin vitropatch-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 300µA.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.

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 Aß-) 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.

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.

Towards a single-use, low-cost endoscope for gastroenterological diagnostics.

Early diagnosis and treatment of diseases in the gastrointestinal (GI) tract including colorectal cancers (CRC) via natural orifices have led to a significant increase in patient survival rates. Most screening procedures utilize image-guided techniques via a conventional endoscope. The cost of conventional endoscopes is substantial, ranging in the tens of thousands of USD or more. This presents significant burden for developing countries, which are disproportionally affected by gastroenterological diseases. Conventional endoscopes also require sterilization between use. This increases the chance of cross-infection between patients. To address these problems, this paper introduces a soft endoscope with a disposable insertion tube that can be articulated. This prototype device is hydraulically actuated, capable of a 10 mm bend radius and 180-degree bend angle. The camera system provides 110 degrees field-of-view. The component parts of this disposable endoscope costs less than 200 USD.Clinical relevance-Our low-cost, single-use endoscope eliminates the sterilization step required by conventional systems, thereby reducing the risks of infection and lowering the operating costs. There is also significant scope for our device to be used beyond the human GI track, such as screening for lung or bladder cancers. Given the compact footprint, the minimal cost of the disposable parts, the proposed platform can widen cancer screening programs with quantifiable economic benefit for many patients, particularly those in developing countries.

Modulating individual axons and axonal populations in the peripheral nerve using transverse intrafascicular multichannel electrodes.

Objective.A transverse intrafascicular multichannel electrode (TIME) may offer advantages over more conventional cuff electrodes including higher spatial selectivity and reduced stimulation charge requirements. However, the performance of TIME, especially in the context of non-conventional stimulation waveforms, remains relatively unexplored. As part of our overarching goal of investigating stimulation efficacy of TIME, we developed a computational toolkit that automates the creation and usage ofin siliconerve models with TIME setup, which solves nerve responses using cable equations and computes extracellular potentials using finite element method.Approach.We began by implementing a flexible and scalable Python/MATLAB-based toolkit for automatically creating models of nerve stimulation in the hybrid NEURON/COMSOL ecosystems. We then developed a sciatic nerve model containing 14 fascicles with 1,170 myelinated (A-type, 30%) and unmyelinated (C-type, 70%) fibers to study fiber responses over a variety of TIME arrangements (monopolar and hexapolar) and stimulation waveforms (kilohertz stimulation and cathodic ramp modulation).Main results.Our toolkit obviates the conventional need to re-create the same nerve in two disparate modeling environments and automates bi-directional transfer of results. Our population-based simulations suggested that kilohertz stimuli provide selective activation of targeted C fibers near the stimulating electrodes but also tended to activate non-targeted A fibers further away. However, C fiber selectivity can be enhanced by hexapolar TIME arrangements that confined the spatial extent of electrical stimuli. Improved upon prior findings, we devised a high-frequency waveform that incorporates cathodic DC ramp to completely remove undesirable onset responses.Conclusion.Our toolkit allows agile, iterative design cycles involving the nerve and TIME, while minimizing the potential operator errors during complex simulation. The nerve model created by our toolkit allowed us to study and optimize the design of next-generation intrafascicular implants for improved spatial and fiber-type selectivity.

Catheter-Directed Thrombolysis for Acute Digit Ischemia in the Setting of Heterozygous Factor V Leiden Mutation: A Case Report and Review of Literature.

CASE: We are reporting the successful treatment of a patient with a heterozygous factor V Leiden mutation who presented with spontaneous thrombotic ischemia of ring and small fingers. Microcatheter-directed administration of thrombolytics at the level of common and proper digital arteries resulted in the salvage of the ring finger to the level of the distal tuft and the entirety of the small finger. CONCLUSION: Heterozygous factor V Leiden mutation is an extremely unusual etiology for thrombotic digital ischemia. This case report emphasizes the importance of correct diagnosis, timely intervention, and thrombolytic therapy using microcatheters to optimize digital rescue.

Simulating the impact of photoreceptor loss and inner retinal network changes on electrical activity of the retina.

Objective.A major reason for poor visual outcomes provided by existing retinal prostheses is the limited knowledge of the impact of photoreceptor loss on retinal remodelling and its subsequent impact on neural responses to electrical stimulation. Computational network models of the neural retina assist in the understanding of normal retinal function but can be also useful for investigating diseased retinal responses to electrical stimulation.Approach.We developed and validated a biophysically detailed discrete neuronal network model of the retina in the software package NEURON. The model includes rod and cone photoreceptors, ON and OFF bipolar cell pathways, amacrine and horizontal cells and finally, ON and OFF retinal ganglion cells with detailed network connectivity and neural intrinsic properties. By accurately controlling the network parameters, we simulated the impact of varying levels of degeneration on retinal electrical function.Main results.Our model was able to reproduce characteristic monophasic and biphasic oscillatory patterns seen in ON and OFF neurons during retinal degeneration (RD). Oscillatory activity occurred at 3 Hz with partial photoreceptor loss and at 6 Hz when all photoreceptor input to the retina was removed. Oscillations were found to gradually weaken, then disappear when synapses and gap junctions were destroyed in the inner retina. Without requiring any changes to intrinsic cellular properties of individual inner retinal neurons, our results suggest that changes in connectivity alone were sufficient to give rise to neural oscillations during photoreceptor degeneration, and significant network connectivity destruction in the inner retina terminated the oscillations.Significance.Our results provide a platform for further understanding physiological retinal changes with progressive photoreceptor and inner RD. Furthermore, our model can be used to guide future stimulation strategies for retinal prostheses to benefit patients at different stages of disease progression, particularly in the early and mid-stages of RD.

Improving the spatial resolution of artificial vision using midget retinal ganglion cell populations modeled at the human fovea.

Objective. Retinal prostheses seek to create artificial vision by stimulating surviving retinal neurons of patients with profound vision impairment. Notwithstanding tremendous research efforts, the performance of all implants tested to date has remained rudimentary, incapable of overcoming the threshold for legal blindness. To maximize the perceptual efficacy of retinal prostheses, a device must be capable of controlling retinal neurons with greater spatiotemporal precision. Most studies of retinal stimulation were derived from either non-primate species or the peripheral primate retina. We investigated if artificial stimulation could leverage the high spatial resolution afforded by the neural substrates at the primate fovea and surrounding regions to achieve improved percept qualities.Approach.We began by developing a new computational model capable of generating anatomically accurate retinal ganglion cell (RGC) populations within the human central retina. Next, multiple RGC populations across the central retina were stimulatedin-silicoto compare clinical and recently proposed neurostimulation configurations based on their ability to improve perceptual efficacy and reduce activation thresholds.Main results.Our model uniquely upholds eccentricity-dependent characteristics such as RGC density and dendritic field diameter, whilst incorporating anatomically accurate features such as axon projection and three-dimensional (3D) RGC layering, features often forgone in favor of reduced computational complexity. Following epiretinal stimulation, the RGCs in our model produced response patterns in shapes akin to the complex and non-trivial percepts reported in clinical trials. Our results also demonstrated that even within the neuron-dense central retina, epiretinal stimulation using a multi-return hexapolar electrode arrangement could reliably achieve spatially focused RGC activation and could achieve single-cell excitation in 56% of all tested locations.Significance. This study establishes an anatomically accurate 3D model of RGC populations within the human central retina and demonstrates the potential for an epiretinal hexapolar configuration to achieve consistent, spatially confined retinal responses, even within the unique and neuron-dense foveal region. Our results and model promote the prospect and optimization of higher spatial resolution in future epiretinal implants.

Diabetes Technology Experiences Among Latinx and Non-Latinx Youth with Type 1 Diabetes.

BACKGROUND: Diabetes technologies, such as insulin pumps and continuous glucose monitors (CGM), have been associated with improved glycemic control and increased quality of life for young people with type 1 diabetes (T1D); however, few young people use these devices, especially those from minority ethnic groups. Current literature predominantly focuses on white patients with private insurance and does not report experiences of diverse pediatric patients with limited resources. METHODS: To explore potential differences between Latinx and non-Latinx patients, English- and Spanish-speaking young people with T1D (n = 173, ages 11-25 years) were surveyed to assess attitudes about and barriers to diabetes technologies using the Technology Use Attitudes and Barriers to Device Use questionnaires. RESULTS: Both English- and Spanish-speaking participants who identified as Latinx were more likely to have public insurance (P = .0001). English-speaking Latinx participants reported higher Hemoglobin A1c values (P = .003), less CGM use (P = .002), and more negative attitudes about technology (generally, P = .003; and diabetes-specific, P < .001) than either non-Latinx or Spanish-speaking Latinx participants. Barriers were encountered with equivalent frequency across groups. CONCLUSIONS: Latinx English-speaking participants had less positive attitudes toward general and diabetes technology than Latinx Spanish-speaking and non-Latinx English-speaking peers, and differences in CGM use were associated with socioeconomic status. Additional work is needed to design and deliver diabetes interventions that are of interest to and supportive of patients from diverse ethnic and language backgrounds.

A Computational Model of Functionally-distinct Cervical Vagus Nerve Fibers.

Cervical vagus nerve stimulation (VNS) is a neuromodulation therapy used in the treatment of several chronic disorders. In order to maximize the therapeutic effectiveness of VNS, it has become increasingly important to deliver fiber-specific neurostimulation, so that undesired effects can be minimized. Assessing the activation of different vagal fiber types through electrical stimulation is therefore essential for developing fiber-selective VNS therapies. Towards this goal, we conducted in silico investigations using a generic model of functionally distinct nerve fibers and clinically relevant cuff electrodes using COMSOL. Our model is constrained by histological observations from rat cervical vagus nerves and its outputs are validated against averaged compound nerve action potentials (CNAPs) obtained from rat vagus nerve recordings. We propose this model as an effective tool to design fiber-specific stimulation protocols before testing them in experimental animals.

Towards Controlling Functionally-Distinct Retinal Ganglion Cells In Degenerate Retina.

Present retinal neuroprostheses have limited performance capabilities due to indiscriminate activation of different neural pathways. Based on our success in differentially activating ON and OFF cells using high frequency stimuli in a healthy retina, in this study we explored whether we could achieve similar differential activation between these two cell types but in degenerate retina. We found that after blocking the synaptic network, ON retinal ganglion cells (RGCs) could be differentially activated at higher frequencies (4 - 6 kHz) and amplitudes (200 - 240 µA), and OFF RGCs at relatively lower amplitudes (80 - 160 µA) across all tested frequencies. We further found that both cell types could be controlled by quickly modulating the frequency using short stimulation bursts. This work takes us one step closer to reducing the likelihood of indiscriminate activation of RGCs by accurately controlling the activation of functionally-distinct neural pathways.

Neural activity of functionally different retinal ganglion cells can be robustly modulated by high-rate electrical pulse trains.

OBJECTIVE: This study focused on characterising the response of four major functionally-different retinal ganglion cells (RGCs) to a high frequency stimulus (HFS) paradigm. APPROACH: We used in vitro patch clamp experiments to assess the viability of evoking a differential response between different RGC types-OFF-Sustained, OFF-Transient, ON-Sustained and ON-Transient-under a wide range of HFS and stimulation amplitude combinations. MAIN RESULTS: Of the four types, we found that the OFF-Sustained, OFF-Transient and ON-Transient RGCs could be differentially activated at various frequency and amplitude combinations, in particular, OFF-Sustained cells can be differentially targeted between 20-100 µA at all frequencies, OFF-Transient cells between 150-240 µA at 1 kHz and ON-Transient between 180-240 µA and 4-6 kHz. We further found that this differential activation held true when the stimulus duration was reduced from 300 ms to 50 ms. Finally, we found that the cell spiking response was not primarily dependent on total charge contained in the pulse train or current amplitude alone, but a combination of amplitude and frequency. SIGNIFICANCE: These results indicate that HFS may be a promising method to target functionally-distinct neural pathways in the retina in an effort to improve the vision quality with retinal prostheses.

Mediating Retinal Ganglion Cell Spike Rates Using High-Frequency Electrical Stimulation.

Recent retinal studies have directed more attention to sophisticated stimulation strategies based on high-frequency (>1.0 kHz) electrical stimulation (HFS). In these studies, each retinal ganglion cell (RGC) type demonstrated a characteristic stimulus-strength-dependent response to HFS, offering the intriguing possibility of focally targeting retinal neurons to provide useful visual information by retinal prosthetics. Ionic mechanisms are known to affect the responses of electrogenic cells during electrical stimulation. However, how these mechanisms affect RGC responses is not well understood at present, particularly when applying HFS. Here, we investigate this issue via an in silico model of the RGC. We calibrate and validate the model using an in vitro retinal preparation. An RGC model based on accurate biophysics and realistic representation of cell morphology, was used to investigate how RGCs respond to HFS. The model was able to closely replicate the stimulus-strength-dependent suppression of RGC action potentials observed experimentally. Our results suggest that spike inhibition during HFS is due to local membrane hyperpolarization caused by outward membrane currents near the stimulus electrode. In addition, the extent of HFS-induced inhibition can be largely altered by the intrinsic properties of the inward sodium current. Finally, stimulus-strength-dependent suppression can be modulated by a wide range of stimulation frequencies, under generalized electrode placement conditions. In vitro experiments verified the computational modeling data. This modeling and experimental approach can be extended to further our understanding on the effects of novel stimulus strategies by simulating RGC stimulus-response profiles over a wider range of stimulation frequencies and electrode locations than have previously been explored.

Computational Models And Tools For Developing Sophisticated Stimulation Strategies For Retinal Neuroprostheses.

Improvements to the efficacy of retinal neuroprostheses can be achieved by developing more sophisticated neural stimulation strategies to enable selective or preferential activation of specific retinal ganglion cells (RGCs). Computational models are particularly well suited for these investigations. The electric field can be accurately described by mathematical formalisms, and the population-based neural responses to the electrical stimulation can be investigated at resolutions well beyond those achievable by current state-of-the-art biological techniques. In this study, we used a biophysically-and morphologically-detailed RGC model to explore the ability of high frequency electrical stimulation (HFS) to preferentially activate ON and OFF RGC subtypes, the two major information pathways of the retina. The performance of a wide range of electrical stimulation amplitudes (0 - $100~\mu \mathbf {A}$) and frequencies (1 - 10 kHz) on functionally-distinct RGC responses were evaluated. We found that ON RGCs could be preferentially activated at relatively higher stimulation amplitudes $( > 50 {\mu } \mathrm {A})$ and frequencies $( >2$ kHz) while OFF RGCs were activated by lower stimulation amplitudes (10 to $50 {\mu } \mathrm {A})$ across all tested frequencies. These stimuli also show great promise in eliciting RGC responses that parallel RGC encoding: one RGC type exhibited an increase in spiking activity during electrical stimulation whilst another exhibited decreased spiking activity, given the same stimulation parameters.

Correction to "Statistically Reconstructed Multiplexing for Very Dense, High-Channel-Count Acquisition Systems".

Presents corrections to the paper, "Statistically reconstructed multiplexing for very dense, high-channel-count acquisition systems," (Tsai, D., et al), IEEE Trans. Biomed. Circuits Syst., vol. 8, no. 1, pp. 13-23, Feb. 2018.

Differential electrical responses in retinal ganglion cell subtypes: effects of synaptic blockade and stimulating electrode location.

OBJECTIVE: Visual prostheses have shown promising results in restoring visual perception to blind patients. The ability to differentially activate retinal ganglion cell (RGC) subtypes could further improve the efficacy of these medical devices. APPROACH: Using whole-cell patch clamp, we investigated membrane potential differences between ON and OFF RGCs in the mouse retina when their synaptic inputs were blocked by synaptic blockers, and examined the differences in stimulation thresholds under such conditions. By injecting intracellular current, we further confirmed the relationship between RGC stimulation thresholds and resting membrane potentials (RMPs). In addition, we investigated the effects of stimulating electrode location on the differences in stimulation thresholds between ON and OFF RGCs. MAIN RESULTS: With synaptic blockade, ON RGCs became significantly more hyperpolarized (from -61.8 ± 1.4 mV to -70.8 ± 1.6 mV), while OFF RGCs depolarized slightly (from -60.5 ± 0.7 mV to -58.6 ± 0.9 mV). RGC stimulation thresholds were negatively correlated with their RMPs (Pearson r value: -0.5154; p-value: 0.0042). Thus, depriving ON RGCs of synaptic inputs significantly increased their thresholds (from 14.7 ± 1.3 µA to 22.3 ± 2.1 µA) over those of OFF RGCs (from 13.2 ± 0.7 µA to 13.1 ± 1.1 µA). However, with control solution, ON and OFF RGC stimulation thresholds were not significantly different. Finally, placement of the stimulating electrode away from the axon enhanced differences in stimulation thresholds between ON and OFF RGCs, facilitating preferential activation of OFF RGCs. SIGNIFICANCE: Since ON and OFF RGCs have antagonistic responses to natural light, achieving differential RGC activation could convey more natural visual information, leading to better visual prosthesis outcomes.

SEEG initiative estimates of Brazilian greenhouse gas emissions from 1970 to 2015.

This work presents the SEEG platform, a 46-year long dataset of greenhouse gas emissions (GHG) in Brazil (1970-2015) providing more than 2 million data records for the Agriculture, Energy, Industry, Waste and Land Use Change Sectors at national and subnational levels. The SEEG dataset was developed by the Climate Observatory, a Brazilian civil society initiative, based on the IPCC guidelines and Brazilian National Inventories embedded with country specific emission factors and processes, raw data from multiple official and non-official sources, and organized together with social and economic indicators. Once completed, the SEEG dataset was converted into a spreadsheet format and shared via web-platform that, by means of simple queries, allows users to search data by emission sources and country and state activities. Because of its effectiveness in producing and making available data on a consistent and accessible basis, SEEG may significantly increase the capacity of civil society, scientists and stakeholders to understand and anticipate trends related to GHG emissions as well as its implications to public policies in Brazil.

Closed-Loop Efficient Searching of Optimal Electrical Stimulation Parameters for Preferential Excitation of Retinal Ganglion Cells.

The ability for visual prostheses to preferentially activate functionally-distinct retinal ganglion cells (RGCs) is important for improving visual perception. This study investigates the use of high frequency stimulation (HFS) to elicit RGC activation, using a closed-loop algorithm to search for optimal stimulation parameters for preferential ON and OFF RGC activation, resembling natural physiological neural encoding in response to visual stimuli. We evaluated the performance of a wide range of electrical stimulation amplitudes and frequencies on RGC responses in vitro using murine retinal preparations. It was possible to preferentially excite either ON or OFF RGCs by adjusting amplitudes and frequencies in HFS. ON RGCs can be preferentially activated at relatively higher stimulation amplitudes (>150 µA) and frequencies (2-6.25 kHz) while OFF RGCs are activated by lower stimulation amplitudes (40-90 µA) across all tested frequencies (1-6.25 kHz). These stimuli also showed great promise in eliciting RGC responses that parallel natural RGC encoding: ON RGCs exhibited an increase in spiking activity during electrical stimulation while OFF RGCs exhibited decreased spiking activity, given the same stimulation amplitude. In conjunction with the in vitro studies, in silico simulations indicated that optimal HFS parameters could be rapidly identified in practice, whilst sampling spiking activity of relevant neuronal subtypes. This closed-loop approach represents a step forward in modulating stimulation parameters to achieve appropriate neural encoding in retinal prostheses, advancing control over RGC subtypes activated by electrical stimulation.