A wearable device perspective on the standard definitions of disability progression in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a leading cause of disability among young adults, but standard clinical scales may not accurately detect subtle changes in disability occurring between visits. This study aims to explore whether wearable device data provides more granular and objective measures of disability progression in MS. METHODS: Remote Assessment of Disease and Relapse in Central Nervous System Disorders (RADAR-CNS) is a longitudinal multicenter observational study in which 400 MS patients have been recruited since June 2018 and prospectively followed up for 24 months. Monitoring of patients included standard clinical visits with assessment of disability through use of the Expanded Disability Status Scale (EDSS), 6-minute walking test (6MWT) and timed 25-foot walk (T25FW), as well as remote monitoring through the use of a Fitbit. RESULTS: Among the 306 patients who completed the study (mean age, 45.6 years; females 67%), confirmed disability progression defined by the EDSS was observed in 74 patients, who had approximately 1392 fewer daily steps than patients without disability progression. However, the decrease in the number of steps experienced over time by patients with EDSS progression and stable patients was not significantly different. Similar results were obtained with disability progression defined by the 6MWT and the T25FW. CONCLUSION: The use of continuous activity monitoring holds great promise as a sensitive and ecologically valid measure of disability progression in MS.

Automatic Assessment of the 2-Minute Walk Distance for Remote Monitoring of People with Multiple Sclerosis.

The aim of this study was to investigate the feasibility of automatically assessing the 2-Minute Walk Distance (2MWD) for monitoring people with multiple sclerosis (pwMS). For 154 pwMS, MS-related clinical outcomes as well as the 2MWDs as evaluated by clinicians and derived from accelerometer data were collected from a total of 323 periodic clinical visits. Accelerometer data from a wearable device during 100 home-based 2MWD assessments were also acquired. The error in estimating the 2MWD was validated for walk tests performed at hospital, and then the correlation (r) between clinical outcomes and home-based 2MWD assessments was evaluated. Robust performance in estimating the 2MWD from the wearable device was obtained, yielding an error of less than 10% in about two-thirds of clinical visits. Correlation analysis showed that there is a strong association between the actual and the estimated 2MWD obtained either at hospital (r = 0.71) or at home (r = 0.58). Furthermore, the estimated 2MWD exhibits moderate-to-strong correlation with various MS-related clinical outcomes, including disability and fatigue severity scores. Automatic assessment of the 2MWD in pwMS is feasible with the usage of a consumer-friendly wearable device in clinical and non-clinical settings. Wearable devices can also enhance the assessment of MS-related clinical outcomes.

Autonomic response to walk tests is useful for assessing outcome measures in people with multiple sclerosis.

Objective: The aim of this study was to evaluate the association between changes in the autonomic control of cardiorespiratory system induced by walk tests and outcome measures in people with Multiple Sclerosis (pwMS). Methods: Electrocardiogram (ECG) recordings of 148 people with Relapsing-Remitting MS (RRMS) and 58 with Secondary Progressive MS (SPMS) were acquired using a wearable device before, during, and after walk test performance from a total of 386 periodical clinical visits. A subset of 90 participants repeated a walk test at home. Various MS-related symptoms, including fatigue, disability, and walking capacity were evaluated at each clinical visit, while heart rate variability (HRV) and ECG-derived respiration (EDR) were analyzed to assess autonomic nervous system (ANS) function. Statistical tests were conducted to assess differences in ANS control between pwMS grouped based on the phenotype or the severity of MS-related symptoms. Furthermore, correlation coefficients (r) were calculated to assess the association between the most significant ANS parameters and MS-outcome measures. Results: People with SPMS, compared to RRMS, reached higher mean heart rate (HRM) values during walk test, and larger sympathovagal balance after test performance. Furthermore, pwMS who were able to adjust their HRM and ventilatory values, such as respiratory rate and standard deviation of the ECG-derived respiration, were associated with better clinical outcomes. Correlation analyses showed weak associations between ANS parameters and clinical outcomes when the Multiple Sclerosis phenotype is not taken into account. Blunted autonomic response, in particular HRM reactivity, was related with worse walking capacity, yielding r = 0.36 r = 0.29 (RRMS) and r > 0.5 (SPMS). A positive strong correlation r > 0.7 r > 0.65 between cardiorespiratory parameters derived at hospital and at home was also found. Conclusion: Autonomic function, as measured by HRV, differs according to MS phenotype. Autonomic response to walk tests may be useful for assessing clinical outcomes, mainly in the progressive stage of MS. Participants with larger changes in HRM are able to walk longer distance, while reduced ventilatory function during and after walk test performance is associated with higher fatigue and disability severity scores. Monitoring of disorder severity could also be feasible using ECG-derived cardiac and respiratory parameters recorded with a wearable device at home.

Biopsychosocial Response to the COVID-19 Lockdown in People with Major Depressive Disorder and Multiple Sclerosis.

BACKGROUND: Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDDs) and Multiple Sclerosis (MS). METHODS: Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse-Central Nervous System) program. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender. RESULTS: Participants with MDDs (N = 255) and MS (N = 214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. A lower mean HR and HR variation were observed between pre and during lockdown during the day for MDDs and during the night for MS. HR variation during rest periods also decreased between pre- and post-lockdown in both clinical conditions. We observed a reduction in physical activity for MDDs and MS upon the introduction of lockdowns. The group with MDDs exhibited a net increase in social interaction via social network apps over the three periods. CONCLUSIONS: Behavioral responses to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDDs and MS. Remote technology monitoring might promptly activate an early warning of physical and social alterations in these stressful situations. Future studies must explore how stress does or does not impact depression severity.

The utility of wearable devices in assessing ambulatory impairments of people with multiple sclerosis in free-living conditions.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a progressive inflammatory and neurodegenerative disease of the central nervous system affecting over 2.5 million people globally. In-clinic six-minute walk test (6MWT) is a widely used objective measure to evaluate the progression of MS. Yet, it has limitations such as the need for a clinical visit and a proper walkway. The widespread use of wearable devices capable of depicting patients' activity profiles has the potential to assess the level of MS-induced disability in free-living conditions. METHODS: In this work, we extracted 96 features in different temporal granularities (from minute-level to day-level) from wearable data and explored their utility in estimating 6MWT scores in a European (Italy, Spain, and Denmark) MS cohort of 337 participants over an average of 10 months' duration. We combined these features with participants' demographics using three regression models including elastic net, gradient boosted trees and random forest. In addition, we quantified the individual feature's contribution using feature importance in these regression models, linear mixed-effects models, generalized estimating equations, and correlation-based feature selection (CFS). RESULTS: The results showed promising estimation performance with R2 of 0.30, which was derived using random forest after CFS. This model was able to distinguish the participants with low disability from those with high disability. Furthermore, we observed that the minute-level (≤ 8 minutes) step count, particularly those capturing the upper end of the step count distribution, had a stronger association with 6MWT. The use of a walking aid was indicative of ambulatory function measured through 6MWT. CONCLUSIONS: This study demonstrates the utility of wearables devices in assessing ambulatory impairments in people with MS in free-living conditions and provides a basis for future investigation into the clinical relevance.

Fitbeat: COVID-19 estimation based on wristband heart rate using a contrastive convolutional auto-encoder.

This study proposes a contrastive convolutional auto-encoder (contrastive CAE), a combined architecture of an auto-encoder and contrastive loss, to identify individuals with suspected COVID-19 infection using heart-rate data from participants with multiple sclerosis (MS) in the ongoing RADAR-CNS mHealth research project. Heart-rate data was remotely collected using a Fitbit wristband. COVID-19 infection was either confirmed through a positive swab test, or inferred through a self-reported set of recognised symptoms of the virus. The contrastive CAE outperforms a conventional convolutional neural network (CNN), a long short-term memory (LSTM) model, and a convolutional auto-encoder without contrastive loss (CAE). On a test set of 19 participants with MS with reported symptoms of COVID-19, each one paired with a participant with MS with no COVID-19 symptoms, the contrastive CAE achieves an unweighted average recall of 95.3 % , a sensitivity of 100 % and a specificity of 90.6 % , an area under the receiver operating characteristic curve (AUC-ROC) of 0.944, indicating a maximum successful detection of symptoms in the given heart rate measurement period, whilst at the same time keeping a low false alarm rate.

Real-time assessment of COVID-19 prevalence among multiple sclerosis patients: a multicenter European study.

We assessed the prevalence and impact of COVID-19 among multiple sclerosis (MS) patients across Europe by leveraging participant data collected as part of the ongoing EU IMI2 RADAR-CNS major programme aimed at finding new ways of monitoring neurological disorders using wearable devices and smartphone technology. In the present study, 399 patients of RADAR-MS have been included (mean age 43.9 years, 60.7% females) with 87/399 patients (21.8%) reporting major symptoms suggestive of COVID-19. A trend for an increased risk of COVID-19 symptoms under alemtuzumab and cladribine treatments in comparison to injectables was observed. Remote monitoring technologies may support health authorities in monitoring and containing the ongoing pandemic.

Estatuto ontológico del embrión humano como persona: una perspectiva desde la investigación biológica en América Latina / Ontological statute of the human embryo as a person: a perspective from biological research in Latin America / Estatuto ontológico do embrião humano como pessoa: uma perspectiva a partir da investigação biológica na América Latina

La utilización de embriones humanos en la investigación biológica ha generado un debate ético desde la discusión ontológica, en relación a si se puede o no considerar al embrión persona humana. En este artículo se análiza el estatuto ontológico del embrión humano desde una perspectiva biológica, considerando las principales líneas de investigación que lo intervienen en América Latina. Adcionalmente, revisamos el aporte desde el estatuto legal del embrión humano en esta región y la postura desde la formalidad de la investigación cientifica en el cuidado de su utilización. Consideramos finalmente que en América Latina no se ha abordado de manera profunda la discusión en torno al estatuto del embrión humano como persona, quedando la discusión en una dimensión biológica.

The utilization of human embryos in the biological research has generated a bioethical debate from the ontological point of view about whether or not to consider the embryo as a human person. This paper review the ontological statute of the human embryo from a biological perspective considering the principal lines of investigation in Latin America. Complementary to discussion we check the contribution from the legal statute of the human embryo and the position from the formal scientific research in his utilization. Finally, we consider that, in Latin America, the discussion has not been approached in a deep way about the statute of the human embryo as person, staying the discussion in a dimension of the biological thing.

A utilização de embriões humanos na investigação biológica tem gerado um debate ético a partir da discussão ontológica, com relação a se deveria ou não considerar o embrião pessoa humana. Neste artigo se analisa o estatuto ontológico do embrião humano a partir de uma perspectiva biológica, considerando as principais linhas de investigação de intervenção no embrião na América Latina. Adicionalmente, revisamos a contribuição a partir do estatuto legal do embrião humano nesta região e a postura a partir da formalidade da investigação cientifica no cuidado de sua utilização. Consideramos finalmente que na América Latina não se tem abordado de maneira profunda a discussão em torno do estatuto do embrião humano como pessoa, tornando-se a discussão uma dimensão biológica.

Rehabilitación de algunas propiedades químicas de los suelos y del bosque de niebla en veracruz, México con ensambles experimentales de leñosas nativas y casuarina equisetifolia L, Amoen / Rehabilitation of some chemical properties of soils and cloud forest at veracruz, Mexico with experimental assemblages of native woody species and casuarina equisetifolia L, Amoen / Reabilitação de algumas propriedades químicas dos solos e do bosque de neblina em veracruz, México com montagens experimentais de lenhosas nativas e casuarina equisetifolia L, Amoen

En la rehabilitación de un sitio muy degradado donde antes hubo bosque nublado, se exploró el efecto de ensambles experimentales de especies leñosas en algunas propiedades químicas del suelo, así como en el desempeño de las plantas. Brinzales de diez especies leñosas nativas de distintas etapas sucesionales del bosque nublado y la especie exótica Casuarina fueron combinados en cinco ensambles experimentales de distinta composición y riqueza. El impacto de los ensambles fue notable en cinco de las ocho propiedades químicas del suelo analizadas. El ensamble con Casuarina sobresalió de los demás por contener los individuos más altos y los niveles superiores de la mayoría de los nutrientes, notablemente nitrógeno. Más de la mitad de los individuos se establecieron exitosamente durante los dos primeros años del experimento (1999 y 2001). Los ensambles afectaron la supervivencia individual, así como todas las variables de crecimiento analizadas. La formación de una cubierta vegetal ocurrió más rápida y extensamente en los ensambles que solo contenían especies nativas, particularmente encinos, los que resaltaron también con niveles altos de algunos nutrientes. El ensamble más rico en especies mostró atributos intermedios en las variables de suelo y de desarrollo. Se valida la inclusión de Casuarina en suelos degradados para favorecer la acumulación de nutrientes. Los resultados sugieren que la rehabilitación inicial puede favorecerse mediante el establecimiento de ensambles.

On the rehabilitation of a severely degraded site formerly occupied by cloud forest, the impact of five experimental tree species assemblages on some soil chemical properties and plant performance was explored. Seedlings of ten native cloud forest succession tree species and the exotic species Casuarina were combined in five assemblages of different composition and richness. Their effect was noticeable on five out of eight soil properties analyzed. The one that included Casuarina stood out on height, and had the highest levels of most of the nutrients, particularly nitrogen. More than half of the trees sown remained alive after the initial two years of the experiment (1999 and 2001). Assemblages affected individual survival time as well as growth variables. Plant cover was most rapid and extensively formed by the native species assemblages; those that included oaks, showed high levels of some nutrients. The richest assemblage displayed intermediate levels in soil and plant variables. The inclusion of the rapid growth species Casuarina was validated to enhance nutrient accumulation on degraded soils. The results suggest that initial rehabilitation can be achieved by the assemblage establishment.

Na reabilitação de um lugar muito degradado onde antes houve bosque de neblina, se explorou o efeito de montagens experimentais de espécies lenhosas em algumas propriedades químicas do solo, assim como no desempenho das plantas. Mudas de dez espécies lenhosas nativas de distintas etapas sucessionais do bosque nublado e a espécie exótica Casuarina foram combinadas em cinco montagens experimentais de distinta composição e riqueza. O impacto das montagens foi notável em cinco das oito propriedades químicas do solo analisadas. A montagem com Casuarina destacou-se entre as outras por conter os individuos mais altos e os níveis superiores da maioria dos nutrientes, notavelmente nitrogêneo. Mais da metade dos indivíduos se estabeleceram exitosamente durante os dois primeros anos do experimento (1999 e 2001). As montagens afetaram a sobrevivência individual, assim como todas as variáveis de crescimento analisadas. A formação de uma coberta vegetal ocorreu mais rápida e extensamente nas montagens que somente continham espécies nativas, particularmente carvalhos, os que ressaltaram também com níveis altos de alguns nutrientes. A montagem mais rica em espécies mostrou atributos intermédios nas variáveis do solo e de desenvolvimento. Certifica-se a inclusão de Casuarina em solos degradados para favorecer a acumulação de nutrientes. Os resultados sugeren que a reabilitação inicial pode favorecer-se mediante o estabelecimento de montagens.