Intelligent autonomous treatment of bedwetting using non-invasive wearable advanced mechatronics systems and MEMS sensors

Post-void alarm systems to monitor bed wetting in Nocturnal Enuresis (NE) have been deemed unsatisfactory. The aim in this study is to develop a safe, comfortable and non-invasive pre-void wearable alarm and associated technology using advanced mechatronics. Each stage of development includes patient and public involvement and engagement (PPI). The early stage of the development involved children with and without nocturnal enuresis (NE) (and parents) who were tested at a hospital under the supervision of physicians, radiologists, psychologists, and nurses. The readings were simultaneously compared to B-mode images and measurements, acquired from a conventional ultrasound device, and were found to correlate highly. The results showed that determining imminent voiding need is viable using non-invasive sensors. Following on from "proof of concept", a bespoke advanced mechatronics device has been created. The device houses custom electronics, an ultrasound system, intelligent software, a user-friendly smartphone application, bedside alarm box and a dedicated undergarment, along with a self-adhesive gel pad - designed to keep the MEMS sensors aligned with the abdomen. Testing of the device with phantoms and volunteers has been successful in determining bladder volume and associated voiding need. Five miniaturized, and therefore more ergonomic, versions of the device are being developed, with an enabled connection to the cloud platform for location independent control and monitoring. Thereafter, the enhanced device will be tested with children with NE at their homes for 14 weeks, to gain feedback relating to wearability and data collection involving the cloud platform

Wearable Miniaturised Smart Device For Children With Nocturnal Enuresis

This research was designed to evaluate if it is viable to awaken children with urinary incontinence at the pre-void phase using a smart wearable device and enable them to control incontinence with fine-tuned individual parameters determined by the device intelligently. To address this research question, a miniaturised wearable smart device was built in this multidisciplinary research to monitor the non-linear behaviours of the bladder during its expansion with urine intake. The device, with its customisable abilities, sets an individual alarm point to awaken the child with incontinence before voiding. Safety parameters, aesthetics and ergonomic use of the device were investigated through hospital trials with children and the device was improved based on the obtained feedback from these trials. Clinical Relevance: The device will help children learn how to control their incontinence over time

Patient Engagement in Medical Device Design: Refining the Essential Attributes of a Wearable, Pre-Void, Ultrasound Alarm for Nocturnal Enuresis

Background To date, no pre-void wearable alarm exists to treat nocturnal enuresis (NE)—night-time bedwetting, and children with NE and their families are disappointed in relation to the post-void moisture alarms and medicine currently available. Development of a safe, comfortable and non-invasive wearable pre-void alarm and associated technology, using advanced mechatronics, is underway (the MyPAD device). Each stage of development includes patient and public involvement (PPI), particularly with respect to human factors, in collaboration with physicians, radiologists, psychologists, nurses, engineers and designers. Objectives The aim of this study was to help us understand the families’ experience of the condition of enuresis, and to provide opinion relating to existing NE alarms, designed to detect moisture, and most importantly, the initial design of the MyPAD wearable technology. Methods A PPI workshop in the form of a focus group, made up of children with enuresis and their parents, was conducted during the early stage of the MyPAD product development. The key research questions (RQs) were: (RQ1) What were the families’ experiences of using existing post-void enuresis alarms? (RQ2) What do families like about the MyPAD prototype? and (RQ3) What do families not like about the MyPAD prototype? A nurse specialised in terms of NE treatment, including post-void alarms, from the Lancashire Teaching Hospitals NHS Foundation Trust, and two MyPAD design engineers were also present, to explain the MyPAD design concept. Braun and Clarke’s six-phase approach to thematic analysis was implemented, which included familiarisation with the data, initial descriptive coding, identifying themes, reviewing themes, defining and labelling themes and producing a report. Results Four common themes were identified from the focus group discussions: the importance of sleep; children do not want to feel different; parents feel frustrated and concerned; resilience and perseverance. These themes applied across the research questions; for example, sleep disruption was highlighted as an issue with existing post-void alarms and as an important requirement for the design of MyPAD. The evaluation of the early version of the MyPAD device has prompted the consideration of changes to some existing facets of the device, including providing multiple alarm types, more options for the design of the garment that houses the device, and the need for clear, age-appropriate and informative instructions relating to how the device should be used, in order to maximise its performance/efficiency and acceptance. Conclusions The qualitative data derived from the focus group discussion was incredibly valuable as it enabled the research and design team to experience the perspectives of the families in terms of the challenges and conflicts of managing the condition and the limited utility of existing post-void alarms. This has improved our understanding of the social and environmental challenges that will need to be considered during the design process

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Genetic association study of childhood aggression across raters, instruments, and age

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis AGGoverall was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations rg among rater-specific assessment of AGG ranged from rg= 0.46 between self- and teacher-assessment to rg= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range |rg|: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg=∼-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |rg| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.</p

MyPAD: A pre-void alarm device for the treatment of Nocturnal Enuresis (NE)

Patients with Nocturnal Enuresis (NE), particularly children can benefit from non-invasive pre-void alarm systems where current post-void alarm systems in the market to monitor bedwetting have been deemed unsatisfactory. The aim in this study was to develop a safe, comfortable and non-invasive pre-void wearable alarm and associated technology using advanced miniaturised mechatronics

Treatment of Nocturnal Enuresis using miniaturised advanced mechatronics with Artificial Intelligence

Objective: Our study was designed to develop a customisable, wearable medical — so-called — MyPAD device that generates pre-void alarms using miniaturised mechatronics with Artificial Intelligence (AI). Methods and procedures: The developed features include: multiple bespoke ultrasound (US) probes for sensing, a bespoke electronic device housing custom US electronics for signal processing, a bedside alarm box for processing the echoed pulses and generating alarms, and a phantom to mimic the human body. The validation of the system is conducted on the tissue-mimicking phantom and volunteers using Bidirectional Long Short-Term Memory Recurrent Neural Networks (Bi-LSTM-RNN) and Reinforcement Learning (RL). Results: A Se value of 99% and a Sp value of 99.5% with an overall accuracy rate of 99.3% are observed. Conclusion: The obtained results demonstrate successful empirical evidence for the viability of the device, both in monitoring bladder expansion to determine voiding need and in reinforcing the continuous learning and customisation of the device for bladder control through consecutive uses

Genetic association study of childhood aggression across raters, instruments, and age

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.Peer reviewe