A modular, deep learning-based holistic intent sensing system tested with Parkinson’s disease patients and controls

People living with mobility-limiting conditions such as Parkinson’s disease can struggle to physically complete intended tasks. Intent-sensing technology can measure and even predict these intended tasks, such that assistive technology could help a user to safely complete them. In prior research, algorithmic systems have been proposed, developed and tested for measuring user intent through a Probabilistic Sensor Network, allowing multiple sensors to be dynamically combined in a modular fashion. A time-segmented deep-learning system has also been presented to predict intent continuously. This study combines these principles, and so proposes, develops and tests a novel algorithm for multi-modal intent sensing, combining measurements from IMU sensors with those from a microphone and interpreting the outputs using time-segmented deep learning. It is tested on a new data set consisting of a mix of non-disabled control volunteers and participants with Parkinson’s disease, and used to classify three activities of daily living as quickly and accurately as possible. Results showed intent could be determined with an accuracy of 97.4% within 0.5 s of inception of the idea to act, which subsequently improved monotonically to a maximum of 99.9918% over the course of the activity. This evidence supports the conclusion that intent sensing is viable as a potential input for assistive medical devices

Noninvasive options for 'wearing-off' in Parkinson's disease: a clinical consensus from a panel of UK Parkinson's disease specialists

In the past 4 years, two adjunctive treatment options to levodopa have been licensed for use in the UK in patients with Parkinson's disease (PD) and motor fluctuations: opicapone, a third-generation catechol-O-methyl transferase inhibitor, and safinamide, a monoamine oxidase B inhibitor. This clinical consensus outlines the practical considerations relating to motor fluctuations and managing wearing-off in patients with PD, and provides a clinical insight to adjunctive treatment options, including opicapone and safinamide. Practice-based opinion was provided from a multidisciplinary steering Group of eight UK-based movement disorder and PD specialists, including neurologists, geriatricians and a nurse specialist, from England, Scotland and Wales

Outcome Measures for Disease-Modifying Trials in Parkinson's Disease:Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative

BACKGROUND: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach.OBJECTIVE: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials.METHODS: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory.RESULTS: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages.CONCLUSION: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges.</p

Outcome Measures for Disease-Modifying Trials in Parkinson's Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative

BACKGROUND: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. OBJECTIVE: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials. METHODS: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory. RESULTS: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages. CONCLUSION: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges

Ensuring that COVID-19 research is inclusive: guidance from the NIHR INCLUDE project

Objective: To provide guidance to researchers, funders, regulators and study delivery teams to ensure that research on COVID-19 is inclusive, particularly of groups disproportionately affected by COVID-19 and who may have been historically under-served by research. Summary of key points: Groups who are disproportionately affected by COVID-19 include (but are not limited to) older people, people with multiple long-term conditions, people with disabilities, people from Black, Asian and Ethnic minority groups, people living with obesity, people who are socioeconomically deprived and people living in care homes. All these groups are under-served by clinical research, and there is an urgent need to rectify this if COVID-19 research is to deliver relevant evidence for these groups who are most in need. We provide a framework and checklists for addressing key issues when designing and delivering inclusive COVID-19 research, based on the National Institute for Health Research INnovations in CLinical trial design and delivery for the UnDEr-served project roadmap. Strong community engagement, codevelopment and prioritisation of research questions and interventions are essential. Under-served groups should be represented on funding panels and ethics committees, who should insist on the removal of barriers to participation. Exclusion criteria should be kept to a minimum; intervention delivery and outcome measurement should be simple, flexible and tailored to the needs of different groups, and local advice on the best way to reach and engage with under-served communities should be taken by study delivery teams. Data on characteristics that allow identification of under-served groups must be collected, analyses should include these data to enable subgroup comparisons and results should be shared with under-served groups at an early stage. Conclusion: Inclusive COVID-19 research is a necessity, not a luxury, if research is to benefit all the communities it seeks to serve. It requires close engagement with under-served groups and attention to aspects of study topic, design, delivery, analysis and dissemination across the research life cycle

Gene expression meta-analysis of Parkinson’s disease and its relationship with Alzheimer’s disease

Abstract Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the most common neurodegenerative diseases and have been suggested to share common pathological and physiological links. Understanding the cross-talk between them could reveal potentials for the development of new strategies for early diagnosis and therapeutic intervention thus improving the quality of life of those affected. Here we have conducted a novel meta-analysis to identify differentially expressed genes (DEGs) in PD microarray datasets comprising 69 PD and 57 control brain samples which is the biggest cohort for such studies to date. Using identified DEGs, we performed pathway, upstream and protein-protein interaction analysis. We identified 1046 DEGs, of which a majority (739/1046) were downregulated in PD. YWHAZ and other genes coding 14–3-3 proteins are identified as important DEGs in signaling pathways and in protein-protein interaction networks (PPIN). Perturbed pathways also include mitochondrial dysfunction and oxidative stress. There was a significant overlap in DEGs between PD and AD, and over 99% of these were differentially expressed in the same up or down direction across the diseases. REST was identified as an upstream regulator in both diseases. Our study demonstrates that PD and AD share significant common DEGs and pathways, and identifies novel genes, pathways and upstream regulators which may be important targets for therapy in both diseases

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good