Discovering behavioural patterns using conversational technology for in-home health and well-being monitoring

Advancements in conversational AI have created unparalleled opportunities to promote the independence and well-being of older adults, including people living with dementia (PLWD). However, conversational agents have yet to demonstrate a direct impact in supporting target populations at home, particularly with long-term user benefits and clinical utility. We introduce an infrastructure fusing in-home activity data captured by Internet of Things (IoT) technologies with voice interactions using conversational technology (Amazon Alexa). We collect 3103 person-days of voice and environmental data across 14 households with PLWD to identify behavioural patterns. Interactions include an automated well-being questionnaire and 10 topics of interest, identified using topic modelling. Although a significant decrease in conversational technology usage was observed after the novelty phase across the cohort, steady state data acquisition for modelling was sustained. We analyse household activity sequences preceding or following Alexa interactions through pairwise similarity and clustering methods. Our analysis demonstrates the capability to identify individual behavioural patterns, changes in those patterns and the corresponding time periods. We further report that households with PLWD continued using Alexa following clinical events (e.g., hospitalisations), which offers a compelling opportunity for proactive health and well-being data gathering related to medical changes. Results demonstrate the promise of conversational AI in digital health monitoring for ageing and dementia support and offer a basis for tracking health and deterioration as indicated by household activity, which can inform healthcare professionals and relevant stakeholders for timely interventions. Future work will use the bespoke behavioural patterns extracted to create more personalised AI conversations

Avaliação Da Resposta Terapêutica Ao Tratamento De Manutenção Com Lítio Em Pacientes Com Transtorno Afetivo Bipolar

To identify potential clinical and epidemiological predictors of long-term response to lithium treatment. Methods A total of 40 adult outpatients followed in an university hospital, with confirmed diagnosis of bipolar disorder and with history of lithium use for at least a six months period, had their response to this medication assessed through the use of a standardized instrument. The ALDA scale is based on retrospective clinical data, in our study assessed through a thoroughly reviewed of the medical charts, and is used to evaluate the clinical improvement with the treatment (Criterion A), corrected by the acknowledgement of possible confounding factors, such as duration of the treatment, compliance and concomitant use of additional medications (Criterion B), in order to estimate the response that can be specifically attributable to lithium. Results Our study found an inverse relation between the number of mood episodes with psychotic symptoms and lithium treatment outcome. Conclusion The results reinforce the hypothesis that lithium seems to be less efficacious in patients with bipolar disorder who present psychotic symptoms.65191

Avaliação da resposta terapêutica ao tratamento de manutenção com lítio em pacientes com transtorno afetivo bipolar

Objetive To identify potential clinical and epidemiological predictors of long-term response to lithium treatment. Methods A total of 40 adult outpatients followed in an university hospital, with confirmed diagnosis of bipolar disorder and with history of lithium use for at least a six months period, had their response to this medication assessed through the use of a standardized instrument. The ALDA scale is based on retrospective clinical data, in our study assessed through a thoroughly reviewed of the medical charts, and is used to evaluate the clinical improvement with the treatment (Criterion A), corrected by the acknowledgement of possible confounding factors, such as duration of the treatment, compliance and concomitant use of additional medications (Criterion B), in order to estimate the response that can be specifically attributable to lithium. Results Our study found an inverse relation between the number of mood episodes with psychotic symptoms and lithium treatment outcome. Conclusion The results reinforce the hypothesis that lithium seems to be less efficacious in patients with bipolar disorder who present psychotic symptoms.Objetivo Identificar potenciais preditores clínicos e epidemiológicos de resposta terapêutica ao uso prolongado de lítio. Métodos Um total de 40 pacientes adultos em tratamento ambulatorial em um hospital universitário, com diagnóstico confirmado de transtorno afetivo bipolar e história de pelo menos seis meses de uso de lítio, teve sua resposta a essa medicação avaliada com a utilização de um instrumento padronizado. A escala ALDA leva em consideração informações clínicas obtidas de forma retrospectiva, em nosso estudo, por meio de minuciosa revisão dos prontuários médicos, para julgar a melhora clínica obtida com o tratamento (Critério A), corrigida pela identificação de possíveis fatores confundidores, tais como duração do tratamento, adesão e uso concomitante de outras drogas (Critério B), de forma a estimar a resposta que pode ser atribuída especificamente ao uso do lítio. Resultados Nosso estudo encontrou uma relação inversa entre o número de episódios de humor com a presença de sintomas psicóticos e o desfecho no tratamento com lítio. Conclusão Esses resultados reforçam a hipótese de que o lítio parece ser menos eficaz em pacientes com transtorno afetivo bipolar que manifestam sintomas psicóticos.To identify potential clinical and epidemiological predictors of long-term response to lithium treatment. A total of 40 adult outpatients followed in an university hospital, with confirmed diagnosis of bipolar disorder and with history of lithium use for651916sem informaçãosem informaçãoIdentificar potenciais preditores clínicos e epidemiológicos de resposta terapêutica ao uso prolongado de lítio. Métodos Um total de 40 pacientes adultos em tratamento ambulatorial em um hospital universitário, com diagnóstico confirmado de transtorno af

Turbulence Hierarchy in a Random Fibre Laser

Turbulence is a challenging feature common to a wide range of complex phenomena. Random fibre lasers are a special class of lasers in which the feedback arises from multiple scattering in a one-dimensional disordered cavity-less medium. Here, we report on statistical signatures of turbulence in the distribution of intensity fluctuations in a continuous-wave-pumped erbium-based random fibre laser, with random Bragg grating scatterers. The distribution of intensity fluctuations in an extensive data set exhibits three qualitatively distinct behaviours: a Gaussian regime below threshold, a mixture of two distributions with exponentially decaying tails near the threshold, and a mixture of distributions with stretched-exponential tails above threshold. All distributions are well described by a hierarchical stochastic model that incorporates Kolmogorov's theory of turbulence, which includes energy cascade and the intermittence phenomenon. Our findings have implications for explaining the remarkably challenging turbulent behaviour in photonics, using a random fibre laser as the experimental platform.Comment: 9 pages, 5 figure

Delocalization and spin-wave dynamics in ferromagnetic chains with long-range correlated random exchange

We study the one-dimensional quantum Heisenberg ferromagnet with exchange couplings exhibiting long-range correlated disorder with power spectrum proportional to $1/k^{\alpha}$, where $k$ is the wave-vector of the modulations on the random coupling landscape. By using renormalization group, integration of the equations of motion and exact diagonalization, we compute the spin-wave localization length and the mean-square displacement of the wave-packet. We find that, associated with the emergence of extended spin-waves in the low-energy region for $\alpha > 1$, the wave-packet mean-square displacement changes from a long-time super-diffusive behavior for $\alpha <1$ to a long-time ballistic behavior for $\alpha > 1$. At the vicinity of $\alpha =1$, the mobility edge separating the extended and localized phases is shown to scale with the degree of correlation as $E_c\propto (\alpha -1)^{1/3}$.Comment: PRB to appea

Delocalization in harmonic chains with long-range correlated random masses

We study the nature of collective excitations in harmonic chains with masses exhibiting long-range correlated disorder with power spectrum proportional to $1/k^{\alpha}$, where $k$ is the wave-vector of the modulations on the random masses landscape. Using a transfer matrix method and exact diagonalization, we compute the localization length and participation ratio of eigenmodes within the band of allowed energies. We find extended vibrational modes in the low-energy region for $\alpha > 1$. In order to study the time evolution of an initially localized energy input, we calculate the second moment $M_2(t)$ of the energy spatial distribution. We show that $M_2(t)$, besides being dependent of the specific initial excitation and exhibiting an anomalous diffusion for weakly correlated disorder, assumes a ballistic spread in the regime $\alpha>1$ due to the presence of extended vibrational modes.Comment: 6 pages, 9 figure

Polyglutamine-expanded ataxin-3: a target engagement marker for spinocerebellar ataxia type 3 in peripheral blood

Background: Spinocerebellar ataxia type 3 is a rare neurodegenerative disease caused by a CAG repeat expansion in the ataxin-3 gene. Although no curative therapy is yet available, preclinical gene-silencing approaches to reduce polyglutamine (polyQ) toxicity demonstrate promising results. In view of upcoming clinical trials, quantitative and easily accessible molecular markers are of critical importance as pharmacodynamic and particularly as target engagement markers. Objective: We aimed at developing an ultrasensitive immunoassay to measure specifically polyQ-expanded ataxin-3 in plasma and cerebrospinal fluid (CSF). Methods: Using the novel single molecule counting ataxin-3 immunoassay, we analyzed cross-sectional and longitudinal patient biomaterials. Results: Statistical analyses revealed a correlation with clinical parameters and a stability of polyQ-expanded ataxin-3 during conversion from the pre-ataxic to the ataxic phases. Conclusions: The novel immunoassay is able to quantify polyQ-expanded ataxin-3 in plasma and CSF, whereas ataxin-3 levels in plasma correlate with disease severity. Longitudinal analyses demonstrated a high stability of polyQ-expanded ataxin-3 over a short period. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder SocietyFunding agencies: This project is supported by the EU Joint Programme—Neurodegenerative Disease Research (JPND) through the following funding organizations under the aegis of JPND: Germany, Federal Ministry of Education and Research (BMBF; funding codes 01ED1602A/B); Netherlands, The Netherlands Organisation for Health Research and Development; Portugal, Foundation for Science and Technology (FCT, grant number JPCOFUND/0001/2015), and Regional Fund for Science and Technology of the Azores; and United Kingdom, Medical Research Council. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 643417. In addition, support has been received by the BIONIC project (number 733050822, which has been made possible by ZonMW as part of “Memorabel,” the research and innovation program for dementia, as part of the Dutch national “Deltaplan for Dementia”: zonmw.nl/dementiaresearch), the CAF[1]E project (the National Institutes of Health, USA, grant number 5R01NS104147-02), and a grant from the Selfridges Group Foundation (NR170024). The BIONIC project is a consortium of Radboudumc, LUMC, ADX Neurosciences, and Rhode Island University

Stage-dependent biomarker changes in spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3/Machado-Joseph disease is the most common autosomal dominant ataxia. In view of the development of targeted therapies, knowledge of early biomarker changes is needed. We analyzed cross-sectional data of 292 spinocerebellar ataxia type 3/Machado-Joseph disease mutation carriers. Blood concentrations of mutant ATXN3 were high before and after ataxia onset, whereas neurofilament light deviated from normal 13.3 years before onset. Pons and cerebellar white matter volumes decreased and deviated from normal 2.2 years and 0.6 years before ataxia onset. We propose a staging model of spinocerebellar ataxia type 3/Machado-Joseph disease that includes a biomarker stage characterized by objective indicators of neurodegeneration before ataxia onset. ANN NEUROL 2024;95:400-406T.K., M.S., L.S., J.I., and B.vdW. are members of the European Reference Network for Rare Neurological Diseases (ERN-RD, project number 739510). The ESMI consortium acknowledges Ruth Hossinger for the project management of the ESMI project and for all contributions made toward the success of this project. This publication is an outcome of ESMI, an EU Joint Program – Neurodegenerative Disease Research (JPND) project (see www.jpnd.eu). The project is supported through the following funding organisations under the aegis of JPND: Germany, Federal Ministry of Education and Research (BMBF; funding codes 01ED1602A/B); Netherlands, The Netherlands Organization for Health Research and Development; Portugal, Fundaçao para a Ciência e Tecnologia (funding code JPCOFUND/ 0002/2015); United Kingdom, Medical Research Council (MR/N028767/1). This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 643417. The Azores ESMI Network is currently supported by the Regional Government (Fundo Regional para a Ciência e a Tecnologia-FRCT), under the PRO-SCIENTIA program. At the USA sites, this work was in part supported by the National Ataxia Foundation and the National Institute of Neurological Disorders and Stroke (NINDS) grant R01NS080816. The Center for Magnetic Resonance Research is supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) grant P41 EB027061, the Institutional Center Cores for Advanced Neuroimaging award P30 NS076408 and S10 OD017974 grant. T.K. received research support from the Bundesministerium für Bildung und Forschung (BMBF), the National Institutes of Health (NIH) and Servier. J.F. received funding as a Fellow of the Hertie Network of Excellence in Clinical Neuroscience. M.R. is supported by FCT (CEECIND/03018/2018). B.vdW. received funding from ZonMw, NWO, Gossweiler Foundation, Brugling Fonds, Radboudumc, Hersenstichting, and Christina Foundation. C.O. received funding from NINDS #U01 NS104326; the National Ataxia Foundation; and Robert and Nancy Hall Brain Research Fund. J.S. is supported in part by the National Ataxia Foundation, the Raynor Cerebellum Project, and the MINDlink Foundation. J.J. received grant support from NIH and Friedrich’s Ataxia Research Alliance (FARA). A.T. received research grants from the University Medicine Essen Clinician Scientist Academy (UMEA)/Deutsche Forschungsgemeinschaft (DFG, grant number: FU356/12-2). At the Portuguese sites, M.M.S. and L.P-A. received funding from European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Program, and through the COMPETE 2020 – Operational Program for Competitiveness and Internationalization; and Portuguese national funds via FCT – Fundaçao para a Ciência e a Tecnologia, under the projects: CENTRO-01-0145-FEDER-181240, 2022.06118.PTDC, UIDB/04539/2020, UIDP/04539/2020, LA/P/0058/2020, ViraVector (CENTRO-01-0145-FEDER-022095), Fighting Sars-CoV-2 (CENTRO-01-01D2-FEDER-000002), BDforMJD (CENTRO-01-0145-FEDER-181240 & 2022.06118.PTDC), ModelPolyQ2.0 (CENTRO-01-0145- FEDER-181258), and MJDEDIT (CENTRO-01-0145- FEDER-181266); ARDAT under the IMI2 JU Grant agreement No 945473 supported by the European Union’s H2020 program and EFPIA; by the American Portuguese Biomedical Research Fund (APBRF), National Ataxia Foundation, and the Richard Chin and Lily Lock Machado-Joseph Disease Research Fund. P.S. and M.M.P. were supported by FCT under the fellowship grant SFRH/BD/148451/2019, and 2019 and 2022.11089.BD. C.W. was supported by the Clinician Scientist Program of the Medical Faculty Tübingen (480-0-0). P.G. is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Center UCLH. P.G. also receives support from the North Thames CRN. P.G. and H.G-M work at University College London Hospitals/University College London, which receives a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Center’s funding scheme. P.G. received funding from the Medical Research Council (MR/N028767/1) and CureSCA3 in support of H.G-M’s work

A standardized protocol for blood and cerebrospinal fluid collection and processing for biomarker research in ataxia

The European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative (ESMI) is a consortium established with the ambition to set up the largest European longitudinal trial-ready cohort of Spinocerebellar Ataxia Type 3/Machado Joseph disease (SCA3/MJD), the most common autosomal dominantly inherited ataxia worldwide. A major focus of ESMI has been the identification of SCA3/MJD biomarkers to enable future interventional studies. As biosample collection and processing variables significantly impact the outcomes of biomarkers studies, biosampling procedures standardization was done previously to study visit initiation. Here, we describe the ESMI consensus biosampling protocol, developed within the scope of ESMI, that ultimately might be translated to other neurodegenerative disorders, particularly ataxias, being the first step to protocol harmonization in the field