Towards a Reconfigurable Sense-and-Stimulate Neural Interface Generating Biphasic Interleaved Stimulus

Published versio

A Programmable Neural Interface for Investigating Arbitrary Stimulation Strategies

Accepted versio

Novel technologies in the treatment and monitoring of advanced and relapsed epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death in females in the UK. It has long been recognized to be a set of heterogeneous diseases, with high grade serous being the most common subtype. The majority of patients with EOC present at an advanced stage (FIGO III–IV), and have the largest risk for disease recurrence from which a high percentage will develop resistance to chemotherapy. Despite continual advances in diagnostics, imaging, surgery and treatment of EOC, there has been little variation in the survival rates for patients with EOC. In this review we will introduce novel bioengineering advances in modelling the lymphatic system and real-time tissue monitoring to improve the clinical and therapeutic outcome for patients with EOC. We discuss the advent of the non-invasive 'liquid biopsy' in the surveillance of patients undergoing treatment and follow-up. Finally, we present new bioengineering advances for palliative care of patients to lessen symptoms of patients with ascites and improve quality of life

Fasciculation analysis reveals a novel parameter that correlates with predicted survival in amyotrophic lateral sclerosis

Introduction Prognostic uncertainty in amyotrophic lateral sclerosis (ALS) confounds clinical management planning, patient counseling, and trial stratification. Fasciculations are an early clinical hallmark of disease and can be quantified noninvasively. Using an innovative analytical method, we correlated novel fasciculation parameters with a predictive survival model. Methods Using high-density surface electromyography, we collected biceps recordings from ALS patients on their first research visit. By accessing an online survival prediction tool, we provided eight clinical and genetic parameters to estimate individual patient survival. Fasciculation analysis was performed using an automated algorithm (Surface Potential Quantification Engine), with a Cox proportional hazards model to calculate hazard ratios. Results The median predicted survival for 31 patients was 41 (interquartile range, 31.5-57) months. Univariate hazard ratios were 1.09 (95% confidence interval [CI], 1.03-1.16) for the rate of change of fasciculation frequency (RoCoFF) and 1.10 (95% CI, 1.01-1.19) for the amplitude dispersion rate. Only the RoCoFF remained significant (P = .04) in a multivariate model. Discussion Noninvasive measurement of fasciculations at a single time-point could enhance prognostic models in ALS, where higher RoCoFF values indicate shorter survival

Fasciculations demonstrate daytime consistency in amyotrophic lateral sclerosis

Introduction Fasciculations represent early neuronal hyperexcitability in amyotrophic lateral sclerosis (ALS). To aid calibration as a disease biomarker, we set out to characterize the daytime variability of fasciculation firing. Methods Fasciculation awareness scores were compiled from 19 ALS patients. In addition, 10 ALS patients prospectively underwent high‐density surface electromyographic (HDSEMG) recordings from biceps and gastrocnemius at three time‐points during a single day. Results Daytime fasciculation awareness scores were low (mean: 0.28 muscle groups), demonstrating significant variability (coefficient of variation: 303%). Biceps HDSEMG recordings were highly consistent for fasciculation potential frequency (intraclass correlation coefficient [ICC] = 95%, n = 19) and the interquartile range of fasciculation potential amplitude (ICC = 95%, n = 19). These parameters exhibited robustness to observed fluctuations in data quality parameters. Gastrocnemius demonstrated more modest levels of consistency overall (44% to 62%, n = 20). Discussion There was remarkable daytime consistency of fasciculation firing in the biceps of ALS patients, despite sparse and intermittent awareness among patients’ accounts

Deliverable Raport D4.6 Tools for generating QMRF and QPRF reports

Scientific reports carry significant importance for the straightforward and effective transfer of knowledge, results and ideas. Good practice dictates that reports should be well-structured and concise. This deliverable describes the reporting services for models, predictions and validation tasks that have been integrated within the eNanoMapper (eNM) modelling infrastructure. Validation services have been added to the Jaqpot Quattro (JQ) modelling platform and the nano-lazar read-across framework developed within WP4 to support eNM modelling activities. Moreover, we have proceeded with the development of reporting services for predictions and models, respectively QPRF and QMRF reports. Therefore, in this deliverable, we first describe the three validation schemes created, namely training set split, cross- and external validation in detail and demonstrate their functionality both on API and UI levels. We then proceed with the description of the read across functionalities and finally, we present and describe the QPRF and QMRF reporting services

Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation

A simple, safe and cost-effective treatment protocol in ovarian stimulation is of great importance in IVF practice, especially in the case of previous unsuccessful attempts. hCG has been used as a substitute of LH because of the degree of homology between the two hormones. The main aim of this prospective randomized study was to determine, for the first time, whether low dose hCG added to rFSH for ovarian stimulation could produce better results compared to the addition of rLH in women entering IVF-ET, especially in those women that had previous IVF failures. An additional aim was to find an indicator that would allow us to follow-up ovarian stimulation and, possibly, modify it in order to achieve a better IVF outcome; and that indicator may be the cDNA copies of the LH/hCG receptor. Group A patients (n = 58) were administered hCG and Group B rLH (n = 56) in addition to rFSH in the first days of ovarian stimulation. The number of follicles and oocytes and, most importantly, implantation and pregnancy rates were shown to be statistically significantly higher in the hCG group. This study has also determined, for the first time to our best knowledge, m-RNA for LH/hCG receptors in the lymphocytes of peripheral blood 40 h before ovum pick-up. cDNA levels of the hCG receptor after ovarian stimulation were significantly higher among women receiving hCG compared to those receiving LH. In addition, higher levels were encountered among women with pregnancy compared to those without, although this was not statistically significant due to the small number of pregnancies. It seems that hCG permits a highly effective and more stable occupancy of rLH/hCG receptors and gives more follicles and more oocytes. The determination of cDNA copies could be, in the future, a marker during ovulation induction protocols and of course a predictor for the outcome of ART in the special subgroup of patients with previous failures

High temporal resolution delayed analysis of clinical microdialysate streams

We thank the Wellcome Trust DOH (HICF-0510-080), the EPSRC (EP/H009744/1) (cycling experiments), and the Imperial Confidence in Concept scheme, Ovarian Cancer Action UK (ovarian tissue measurements), the National Science Foundation (CHE-1608757), and the NIH (R01 MH104386) for fundin

Feasibility of mapping and ablating ectopy-triggering ganglionated plexus reproducibly in persistent atrial fibrillation

Background Ablation of autonomic ectopy-triggering ganglionated plexuses (ET-GP) has been used to treat paroxysmal atrial fibrillation (AF). It is not known if ET-GP localisation is reproducible between different stimulators or whether ET-GP can be mapped and ablated in persistent AF. We tested the reproducibility of the left atrial ET-GP location using different high-frequency high-output stimulators in AF. In addition, we tested the feasibility of identifying ET-GP locations in persistent atrial fibrillation. Methods Nine patients undergoing clinically-indicated paroxysmal AF ablation received pacing-synchronised high-frequency stimulation (HFS), delivered in SR during the left atrial refractory period, to compare ET-GP localisation between a custom-built current-controlled stimulator (Tau20) and a voltage-controlled stimulator (Grass S88, SIU5). Two patients with persistent AF underwent cardioversion, left atrial ET-GP mapping with the Tau20 and ablation (Precision™, Tacticath™ [n = 1] or Carto™, SmartTouch™ [n = 1]). Pulmonary vein isolation (PVI) was not performed. Efficacy of ablation at ET-GP sites alone without PVI was assessed at 1 year. Results The mean output to identify ET-GP was 34 mA (n = 5). Reproducibility of response to synchronised HFS was 100% (Tau20 vs Grass S88; [n = 16] [kappa = 1, SE = 0.00, 95% CI 1 to 1)][Tau20 v Tau20; [n = 13] [kappa = 1, SE = 0, 95% CI 1 to 1]). Two patients with persistent AF had 10 and 7 ET-GP sites identified requiring 6 and 3 min of radiofrequency ablation respectively to abolish ET-GP response. Both patients were free from AF for > 365 days without anti-arrhythmics. Conclusions ET-GP sites are identified at the same location by different stimulators. ET-GP ablation alone was able to prevent AF recurrence in persistent AF, and further studies would be warranted