Digital home monitoring for capturing daily fluctuation of symptoms; a longitudinal repeated measures study: Long Covid Multi-disciplinary Consortium to Optimise Treatments and Services across the NHS (a LOCOMOTION study).

INTRODUCTION: A substantial proportion of COVID-19 survivors continue to have symptoms more than 3 months after infection, especially of those who required medical intervention. Lasting symptoms are wide-ranging, and presentation varies between individuals and fluctuates within an individual. Improved understanding of undulation in symptoms and triggers may improve efficacy of healthcare providers and enable individuals to better self-manage their Long Covid. We present a protocol where we aim to develop and examine the feasibility and usability of digital home monitoring for capturing daily fluctuation of symptoms in individuals with Long Covid and provide data to facilitate a personalised approach to the classification and management of Long Covid symptoms. METHODS AND ANALYSIS: This study is a longitudinal prospective cohort study of adults with Long Covid accessing 10 National Health Service (NHS) rehabilitation services in the UK. We aim to recruit 400 people from participating NHS sites. At referral to study, 6 weeks and 12 weeks, participants will complete demographic data (referral to study) and clinical outcome measures, including ecological momentary assessment (EMA) using personal mobile devices. EMA items are adapted from the COVID-19 Yorkshire Rehabilitation Scale items and include self-reported activities, symptoms and psychological factors. Passive activity data will be collected through wrist-worn sensors. We will use latent class growth models to identify trajectories of experience, potential phenotypes defined by co-occurrence of symptoms and inter-relationships between stressors, symptoms and participation in daily activities. We anticipate that n=300 participants provide 80% power to detect a 20% improvement in fatigue over 12 weeks in one class of patients relative to another. ETHICS AND DISSEMINATION: The study was approved by the Yorkshire & The Humber-Bradford Leeds Research Ethics Committee (ref: 21/YH/0276). Findings will be disseminated in peer-reviewed publications and presented at conferences. TRIAL REGISTRATION NUMBER: ISRCTN15022307.

The Effects of Tinnitus in Probabilistic Learning Tasks: Protocol for an Ecological Momentary Assessment Study.

BACKGROUND: Chronic tinnitus is an increasing worldwide health concern, causing a significant burden to the health care system each year. The COVID-19 pandemic has seen a further increase in reported cases. For people with tinnitus, symptoms are exacerbated because of social isolation and the elevated levels of anxiety and depression caused by quarantines and lockdowns. Although it has been reported that patients with tinnitus can experience changes in cognitive capabilities, changes in adaptive learning via decision-making tasks for people with tinnitus have not yet been investigated. OBJECTIVE: In this study, we aim to assess state- and trait-related impairments in adaptive learning ability on probabilistic learning tasks among people with tinnitus. Given that performance in such tasks can be quantified through computational modeling methods using a small set of neural-informed model parameters, such approaches are promising in terms of the assessment of tinnitus severity. We will first examine baseline differences in the characterization of decision-making under uncertainty between healthy individuals and people with tinnitus in terms of differences in the parameters of computational models in a cross-sectional experiment. We will also investigate whether these computational markers, which capture characteristics of decision-making, can be used to understand the cognitive impact of tinnitus symptom fluctuations through a longitudinal experimental design. METHODS: We have developed a mobile app, AthenaCX, to deliver e-consent and baseline tinnitus and psychological assessments as well as regular ecological momentary assessments (EMAs) of perceived tinnitus loudness and a web-based aversive version of a probabilistic decision-making task, which can be triggered based on the participants' responses to the EMA surveys. Computational models will be developed to fit participants' choice data in the task, and cognitive parameters will be estimated to characterize participants' current ability to adapt learning to the change of the simulated environment at each session when the task is triggered. Linear regression analysis will be conducted to evaluate the impacts of baseline tinnitus severity on adapting decision-making performance. Repeated measures linear regression analysis will be used to examine model-derived parameters of decision-making in measuring real-time perceived tinnitus loudness fluctuations. RESULTS: Ethics approval was received in December 2020 from Dublin City University (DCUREC/2021/070). The implementation of the experiments, including both the surveys and the web-based decision-making task, has been prepared. Recruitment flyers have been shared with audiologists, and a video instruction has been created to illustrate to the participants how to participate in the experiment. We expect to finish data collection over 12 months and complete data analysis 6 months after this. The results are expected to be published in December 2023. CONCLUSIONS: We believe that EMA with context-aware triggering can facilitate a deeper understanding of the effects of tinnitus symptom severity upon decision-making processes as measured outside of the laboratory. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/36583.

A comparison of distributed machine learning methods for the support of "many labs" collaborations in computational modeling of decision making.

Deep learning models are powerful tools for representing the complex learning processes and decision-making strategies used by humans. Such neural network models make fewer assumptions about the underlying mechanisms thus providing experimental flexibility in terms of applicability. However, this comes at the cost of involving a larger number of parameters requiring significantly more data for effective learning. This presents practical challenges given that most cognitive experiments involve relatively small numbers of subjects. Laboratory collaborations are a natural way to increase overall dataset size. However, data sharing barriers between laboratories as necessitated by data protection regulations encourage the search for alternative methods to enable collaborative data science. Distributed learning, especially federated learning (FL), which supports the preservation of data privacy, is a promising method for addressing this issue. To verify the reliability and feasibility of applying FL to train neural networks models used in the characterization of decision making, we conducted experiments on a real-world, many-labs data pool including experiment data-sets from ten independent studies. The performance of single models trained on single laboratory data-sets was poor. This unsurprising finding supports the need for laboratory collaboration to train more reliable models. To that end we evaluated four collaborative approaches. The first approach represents conventional centralized learning (CL-based) and is the optimal approach but requires complete sharing of data which we wish to avoid. The results however establish a benchmark for the other three approaches, federated learning (FL-based), incremental learning (IL-based), and cyclic incremental learning (CIL-based). We evaluate these approaches in terms of prediction accuracy and capacity to characterize human decision-making strategies. The FL-based model achieves performance most comparable to that of the CL-based model. This indicates that FL has value in scaling data science methods to data collected in computational modeling contexts when data sharing is not convenient, practical or permissible.

Differences in Learning and Persistency Characterizing Behavior in Chronic Pain for the Iowa Gambling Task: Web-Based Laboratory-in-the-Field Study.

BACKGROUND: Chronic pain is a significant worldwide health problem. It has been reported that people with chronic pain experience decision-making impairments, but these findings have been based on conventional laboratory experiments to date. In such experiments, researchers have extensive control of conditions and can more precisely eliminate potential confounds. In contrast, there is much less known regarding how chronic pain affects decision-making captured via laboratory-in-the-field experiments. Although such settings can introduce more experimental uncertainty, collecting data in more ecologically valid contexts can better characterize the real-world impact of chronic pain. OBJECTIVE: We aim to quantify decision-making differences between individuals with chronic pain and healthy controls in a laboratory-in-the-field environment by taking advantage of internet technologies and social media. METHODS: A cross-sectional design with independent groups was used. A convenience sample of 45 participants was recruited through social media: 20 (44%) participants who self-reported living with chronic pain, and 25 (56%) people with no pain or who were living with pain for <6 months acting as controls. All participants completed a self-report questionnaire assessing their pain experiences and a neuropsychological task measuring their decision-making (ie, the Iowa Gambling Task) in their web browser at a time and location of their choice without supervision. RESULTS: Standard behavioral analysis revealed no differences in learning strategies between the 2 groups, although qualitative differences could be observed in the learning curves. However, computational modeling revealed that individuals with chronic pain were quicker to update their behavior than healthy controls, which reflected their increased learning rate (95% highest-posterior-density interval [HDI] 0.66-0.99) when fitted to the Values-Plus-Perseverance model. This result was further validated and extended on the Outcome-Representation Learning model as higher differences (95% HDI 0.16-0.47) between the reward and punishment learning rates were observed when fitted to this model, indicating that individuals with chronic pain were more sensitive to rewards. It was also found that they were less persistent in their choices during the Iowa Gambling Task compared with controls, a fact reflected by their decreased outcome perseverance (95% HDI -4.38 to -0.21) when fitted using the Outcome-Representation Learning model. Moreover, correlation analysis revealed that the estimated parameters had predictive value for the self-reported pain experiences, suggesting that the altered cognitive parameters could be potential candidates for inclusion in chronic pain assessments. CONCLUSIONS: We found that individuals with chronic pain were more driven by rewards and less consistent when making decisions in our laboratory-in-the-field experiment. In this case study, it was demonstrated that, compared with standard statistical summaries of behavioral performance, computational approaches offered superior ability to resolve, understand, and explain the differences in decision-making behavior in the context of chronic pain outside the laboratory.

A rapid and sensitive method to detect SARS-CoV-2 virus using targeted-mass spectrometry.

In the last few months, there has been a global catastrophic outbreak of severe acute respiratory syndrome disease caused by the novel coronavirus SARS-CoV-2 affecting millions of people worldwide. Early diagnosis and isolation are key to contain the rapid spread of the virus. Towards this goal, we report a simple, sensitive and rapid method to detect the virus using a targeted mass spectrometric approach, which can directly detect the presence of virus from naso-oropharyngeal swabs. Using a multiple reaction monitoring we can detect the presence of two peptides specific to SARS-CoV-2 in a 2.3 min gradient run with 100% specificity and 90.5% sensitivity when compared to RT-PCR. Importantly, we further show that these peptides could be detected even in the patients who have recovered from the symptoms and have tested negative for the virus by RT-PCR highlighting the sensitivity of the technique. This method has the translational potential of in terms of the rapid diagnostics of symptomatic and asymptomatic COVID-19 and can augment current methods available for diagnosis of SARS-CoV-2.

Integrated genomic view of SARS-CoV-2 in India.

Background: India first detected SARS-CoV-2, causal agent of COVID-19 in late January 2020, imported from Wuhan, China. From March 2020 onwards, the importation of cases from countries in the rest of the world followed by seeding of local transmission triggered further outbreaks in India. Methods: We used ARTIC protocol-based tiling amplicon sequencing of SARS-CoV-2 (n=104) from different states of India using a combination of MinION and MinIT sequencing from Oxford Nanopore Technology to understand how introduction and local transmission occurred. Results: The analyses revealed multiple introductions of SARS-CoV-2 genomes, including the A2a cluster from Europe and the USA, A3 cluster from Middle East and A4 cluster (haplotype redefined) from Southeast Asia (Indonesia, Thailand and Malaysia) and Central Asia (Kyrgyzstan). The local transmission and persistence of genomes A4, A2a and A3 was also observed in the studied locations. The most prevalent genomes with patterns of variance (confined in a cluster) remain unclassified, and are here proposed as A4-clade based on its divergence within the A cluster. Conclusions: The viral haplotypes may link their persistence to geo-climatic conditions and host response. Multipronged strategies including molecular surveillance based on real-time viral genomic data is of paramount importance for a timely management of the pandemic.