A device to detect and measure the progression of dementia by quantifying the interactions between neuronal and cardiovascular oscillations

Lead Research Organisation: Lancaster University
Department Name: Physics

Abstract

The social context of the research is the rapidly ageing population, and the fact that the number of people in the UK and the world experiencing dementia is increasing. It is predicted that 66 million individuals worldwide will have dementia in 2030. It was in recognition of this grim situation that the Prime Minister launched the Dementia Challenge in 2012.

The scientific context is that vast resources have been and are being expended on Alzheimer's disease by governments and the pharmaceutical industry. Almost all of these are based on the amyloid-cascade hypothesis. But this approach has not been notably successful to date, and is looking increasingly doubtful. There are now powerful arguments in favour of looking at alternatives and anticipating a paradigm shift in the understanding of Altzheimer's disease and, probably, of many or most other dementias. There are many indicators suggesting that dementia is often connected with nutritional failures at the neuronal level and that these may be reversed, or at least ameliorated, by changes in lifestyle and diet. It will be enormously advantageous if a simple means can be devised to monitor the severity of dementia, and to identify the at-risk population for whom early remedial action is likely to be helpful.

We therefore propose to develop a method of quantifying the degree of dementia, based on physics. It will apply new, sophisticated, analysis methods to brain signals measured from patients, including both electrical (EEG) signals and cardiovascular (blood flow/oxygenation) signals. The intention is to create a device that will be able to provide quantitative measurements of disease progression - or regression in cases where treatment and/or changes in diet or lifestyle are yielding beneficial results.

The device we propose is a system consisting of commercially-available state-of-the-art instruments plus novel data analysis algorithms. Its unique features are that it involves

1. Evaluation of both the cardiovascular and neuronal/cognitive oscillations simultaneously and noninvasively, leading to an assessment of the dysfunction in their mutual interactions.

2. Eventually, a standardised presentation of the results in terms of images and a single coefficient spanning from 0 to 100.

3. A relatively comfortable and inexpensive assessment method (especially when compared to MRI-related methods) that can easily be repeated either in the same day or as frequently as is needed or desired.

We will test the feasibility of the device, and develop the necessary data analysis algorithms, with the help of 10 clinically assessed dementia patients and 10 healthy controls, in Addenbrooke's Hospital (Cambridge). The data analysis will all be carried out in Lancaster using a range sophisticated methods, some of which are completely novel and highly promising. Assuming that the enterprise is successful, it may be expected to lead in turn to clinical trials, including longitudinal studies, but these are beyond the scope of the present proposal. Nonetheless we can expect to achieve proof-of-concept for the device, operating in a clinical environment.

In the longer term, we anticipate that the cost of the device can be substantially reduced, partly by making the near-infra-red-spectrometer (NIRS) purpose-designed, rather than relying on a flexible multi-purpose instrument, and partly by mass-production.

Planned Impact

1. Who will benefit from this research?
Anybody developing a form of dementia is a potential beneficiary, and so correspondingly are the family, social workers, and medical teams that are looking after her or him. The numbers are very large: there were 800,000 people with dementia in the UK in 2012, of whom 17,000 were under 65. It is estimated that by 2021 there will be a million dementia patients in the UK, with a projected growth to 1.7 million by 2051. Looking beyond the UK, to the world as a whole, the predicted number for 2030 is 66 million. There are also potential benefits for industry: for the medical instruments industry in manufacturing the proposed device; and for the pharmaceutical industry in providing an easy-to-use method to follow up and evaluate on a day-to-day basis the effect of treatment. It can of course be used to evaluate any treatment - including drugs, diet, or life style changes.


2. How will they benefit from this research?
The research offers a route to improved diagnosis together with a means of quantifying the severity of the disease. The research is expected to lead to eventually a device that will be easy and reasonably quick (minutes) to use, that is non-invasive, and which does not cause discomfort. It will therefore become feasible to carry out tests at frequent intervals where necessary, to evaluate not only the progression or remission of the disease, but to make explicit evaluations of the efficacy of treatment and the effects of diet, exercise, and lifestyle changes. Although the basic research proposed here requires some relatively expensive general-purpose equipment, it is anticipated that, once we have established exactly what is needed, and with large-scale production, the final device can realistically find a place in every GP's surgery. Manufacturers stand to gain from industrial production of the new device.

Publications

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Hagos Z (2019) Synchronization transitions caused by time-varying coupling functions. in Philosophical transactions. Series A, Mathematical, physical, and engineering sciences

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Lancaster G (2018) Surrogate data for hypothesis testing of physical systems in Physics Reports

 
Description Combined near infrared spectroscopy (NIRS) and electroencephalography (EEG) measurements in healthy humans of different ages have revealed low frequency oscillations in the signals recorded via both techniques. Significant coherence was observed between these oscillations in some cases, and it was found that this coherence is altered with age. Analysis techniques for the extraction of more specific information about neurovascular coupling were developed. The reliable identification of dynamics in biomedical time series has been thoroughly investigated in a review paper on surrogate data testing, to ensure that conclusions arising from the project are robust. A software toolbox MODA (Multiscale Oscillatory Dynamics Analysis) has been developed and is very likely to be useful to a range of other scientists - both medical and non-medical. We investigated oscillations in signals recorded by NIRT - a similar technique to NIRS - and have demonstrated the dominance of low-frequency components related to vasomotion.
Exploitation Route The nature of low-frequency components in NIRS signals is of general importance for brain dynamics, not only for dementia. Further work is needed, but it is obvious that NIRS may eventually replace in many ways more expensive magnetic resonance imaging (MRI), especially because of its excellent time-resolution. NIRS in combination with the electroencephalography (EEG) seems highly promising for lay detection.
The knowledge arising from this project is also being used to inform collaborations in similar fields. A new proposal in collaboration with Psychology at Lancaster is in preparation, and a paper describing the low frequency oscillations in the similar technique of NIR-T/BSS, used for the measurement of subarachnoid space width, has been published in Scientific Reports in February 2018.
Sectors Communities and Social Services/Policy,Digital/Communication/Information Technologies (including Software),Education,Electronics,Healthcare,Government, Democracy and Justice,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Security and Diplomacy

 
Description Extensive outreach in terms of talks to schools, both students visiting Lancaster and staff visiting schools.
First Year Of Impact 2015
Sector Education
Impact Types Cultural

 
Description A novel instrument for non-invasive early diagnosis of malaria
Amount £5,000 (GBP)
Organisation Joy Welch Educational Charitable Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2019 
End 02/2020
 
Description Data Science Research Workshop "Discerning Oscillations in Noisy Time-Series Data"
Amount £5,000 (GBP)
Organisation Lancaster University 
Sector Academic/University
Country United Kingdom
Start 05/2020 
End 10/2020
 
Description LU Impact Fund
Amount £6,980 (GBP)
Organisation Lancaster University 
Sector Academic/University
Country United Kingdom
Start 08/2016 
End 07/2017
 
Description PhD scholarship for Juliane Bjerkan
Amount £197,000 (GBP)
Organisation Sir John Fisher Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2019 
End 10/2022
 
Description The physiological significance of cardiorespiratory interactions: bridging between data analysis, mathematical theory and physiological models. Catalyst Seeding
Amount $80,000 (NZD)
Organisation Royal Society of New Zealand 
Sector Charity/Non Profit
Country New Zealand
Start 11/2018 
End 11/2020
 
Title System to assess neurovascular dynamics 
Description The system uniquely combines 16-channels EEG and 10-channels NIRS with high sampling frequencies. Simultaneously recorded data assessed for individual oscillatory dynamics and spatial and temporal couplings. The strength of oscillations and their couplings is used to asses the functional neurovascular state of the brain. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2016 
Provided To Others? No  
Impact Signatures of ageing in the neurovascular couplings observed. 
 
Title Blocker data 
Description 7 subjects administrated with saline controls as well as atropine and propranolol to investigate autonomic regulation of the cardiovascular system. Data were recorded by Jeffrey Hoag and William Cooke, under the supervision of Dwain L Eckberg at the Virginia Commonwealth University School of Medicine and Department of Veterans Affairs Medical Center, Richmond, Virginia, USA. Data was made available for analysis by the Nonlinear and Biomedical Physics Group in Physics Department by Dwain L Eckberg during his multiple visits to the group. All authors of the data were involved in the interpretation of the results of analysis made by members of the group, and in particular by Philip Clemson. All analyses methods were developed by the group under various projects. A paper reporting the results is under submission for a journal publication. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact A paper is under revision. 
 
Title Healthy neurovascular ageing 
Description Twenty eight 30-min data sets, each containing 16 EEG channels and 10 NIRS channels were recorded in young and older subjects. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? No  
Impact The data is providing a control group for the data to be collected from dementia patients, who are likely to have a wide range of ages. At the same time they form a basis for study of healthy neurovascular ageing with the same methodology. 
 
Title Hypoxia study 
Description Data sets and algorithms used in the Journal of Physiology paper 'Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans', 2020 by G. Lancaster, T. Debevec, G. P. Millet, M. Poussel, S. J. Willis, M. Mramor, K. Goricar, D. Osredkar, V. Dolžan and A. Stefanovska Time series of ECG, respiration and despiked LDF blood flow recordings are provided, and have been downsampled from 1200Hz to 40Hz. Genetics results are also provided for each subject. Group names are based on experimental conditions, as follows: NN - normobaric normoxia NHa - acute normobaric hypoxia NH - normobaric hypoxia after 6 hours acclimatisation HHa - acute hypobaric hypoxia HH - hypobaric hypoxia after 6 hours acclimatisation The study protocol was pre-registered at ClinicalTrials.gov (NCT02780908). 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact Perspectives are in preparation for the paper "Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans" published as an early view in the Journal of Physiology in January 2020. 
 
Title Nonlinear dynamics of malaria 
Description The data sets comprised several cardiovascular parameter such as; blood flow, oxygenation, temperature, respiration, and ECG. Fifty patients with clinically acute febrile and non-febrile malaria were enrolled in the study, in accordance with the inclusion criteria. Fifty one healthy volunteers with no clinical malaria were also enrolled in the study. Owing to commercial sensitivity, the data are available on request to bona fide researchers with a legitimate interest only. Please contact rdm@lancaster.ac.uk for more information. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact Too early. 
 
Title On the suitability of laser-Doppler flowmetry for capturing microvascular blood flow dynamics from darkly pigmented skin 
Description The data set are presented in 1X1 structure with 9 fields. The fields are named as: ECG (Electrocardiogram recordings), Resp (Respiration recordings), Temp1 and Temp2 (Temperature recordings from the left and right ankles), DsLA (blood flow recordings from left ankle), DsRA (blood flow recordings from right ankle) BP (pulse recordings), name and age. Results of analyses of these data are presented in Physiol Meas. 2019 Aug 2;40(7):074005. doi: 10.1088/1361-6579/ab2651. On the suitability of laser-Doppler flowmetry for capturing microvascular blood flow dynamics from darkly pigmented skin. Abdulhameed YA1, Lancaster G, McClintock PVE, Stefanovska A. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact Not known yet. 
 
Title Race-specific differences in the phase coherence between blood flow and oxygenation: A simultaneous NIRS, white light spectroscopy and LDF study 
Description The data sets comprised several cardiovascular parameter such as; blood flow, tissue oxygenation, temperature, respiration, and ECG. Thirty-two healthy male volunteers participating in the study were aged 19 ,5 years (mean ,SD). They were divided into two groups: 16 black Africans (BA) and 16 Caucasian whites (CA), all students at Lancaster University. The BA group was composed of West Africans (from Nigeria and Ghana) plus two black Sudanese, while the CA group was white-skinned British plus two Europeans. Results published in J Biophotonics. 2020 Jan 16:e201960131. doi: 10.1002/jbio.201960131. [Epub ahead of print] Race-specific differences in the phase coherence between blood flow and oxygenation: A simultaneous NIRS, white light spectroscopy and LDF study. Abdulhameed YA, McClintock PVE, Stefanovska A. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact Not known yet. 
 
Title SAS width/BP data 
Description The dataest contains recordings of subarachnoid space (SAS) width using near infrared transillumination backscattering sounding (NIRT) and blood pressure data used in the analysis in "Human subarachnoid space width oscillations in the resting state", Sci. Rep. 8, 3057, 2018. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact The data file is available on request only and was made available only in February 2018, after the publication of the Sci Rep paper, so it is too early to expect an impact. 
 
Description Abdulrazaq Habib 
Organisation Bayero University Kano
Country Nigeria 
Sector Academic/University 
PI Contribution Members of the group designed a study of the nonlinear dynamics in malaria and prepared the equipment and required time-series analysis methods, A PhD student from the group traveled to Kano (Nigeria) and made the measurements in control group and groups with non-fibril and fibril malaria. All subjects were young male thereby maximizing the homogeneity of the groups.Members of the group, supervised by myself, analysed the data and were involved in the interpretation of the results. We conducted several additional studies in Lancaster to evaluate the effect of melanin in optical measurements, and possible differences in cardiovascular dynamics between subjects with Caucasian skin and dark skin, both non-African-born and brought up (but of African origin) and African-born and brought up subjects.
Collaborator Contribution Our collaborator, Professor Abdulrazaq Habib, Consultant Physician in the associated Aminu Kano Teaching Hospital and professor in the Bayero University, Kano, Nigeria, recruited the subjects, undertook clinical screening and helped in interpreting the results.
Impact We identified dynamical biomarkers for non-invasive early detection of malaria and prepared a patent application. Unfortunately, the University could not afford to take the patent application to the next stage. We are now finalizing a manuscript on the joint work.
Start Year 2017
 
Description Alona Ben-Tal 
Organisation Massey University
Country New Zealand 
Sector Academic/University 
PI Contribution As an internationally recognized authority on the oscillatory dynamics of living systems Aneta Stefanovska contributed her expertise and experience in the field. She helped writing the successful proposal on "The physiological significance of cardiovascular interactions: bridging between data analysis, mathematical theory and physiological models".
Collaborator Contribution Dr Alona Ben Tal has been studying different aspects of the cardiorespiratory system for the past 15 years and has developed mathematical models of the mammalian respiratory systems. She drafted the successful Royal Society/New Zealand proposal on "The physiological significance of cardiovascular interactions: bridging between data analysis, mathematical theory and physiological models".
Impact The application for Catalyst fund for a 2-years collaboration between the Nonlinear and Biomedical Physics group in Physics Department at Lancaster University and the Institute of Natural and Material Sciences from Massey University was successful. Aneta Stefanovska visited Masey University in March 2019 and give a public lecture on 12 March on "Biological clocks - adjustable time-keeping makes for good health". Alona Ben Tal and her PhD student Shumaila Noreen visited the group in Lancaster in Jun/July 2019.
Start Year 2018
 
Description Collaboration on effect of ambient temperature on cardiovascular regulation with Dr Maja Elstad and her group in Oslo 
Organisation University of Oslo
Department Institute for Experimental Medical Research
Country Norway 
Sector Academic/University 
PI Contribution Maja Eldtad and I discussed the study design. Our group provides algoriithms. Under my supervission my PhD student Sultan Alatawi analyses data from the study on the effect of ambient temperature on cardiovacular regulation recorded by the Elstad group in Oslo.
Collaborator Contribution Maja Elstad and her group organised the measurements, collected the data and did preliminary analysis. They also interprete the physiological implications of the results.
Impact So far, we published a conference paper together. We are now preparing a series of journal papers based on results of analysis.
Start Year 2016
 
Description Collaboration on hypoxia 
Organisation University of Ljubljana
Department Medical Faculty
Country Slovenia 
Sector Academic/University 
PI Contribution Myself and my group contributed to the study design, the measurement set-up and the analysis of recorded data.
Collaborator Contribution The collaborators, Prof Damjan Osredkar and Prof Tadej Dobevec recruited the subjects, performed the measurements and contributed to the interpretation of results.
Impact The early view (EV) version of our article has been published by the Journal of Physiology. Since 20 February 2020, when it was published, it gain an attention score 90, which is In the top 5% of all research outputs scored by Altmetric.
Start Year 2017
 
Description Dementia collaboration in Lancaster 
Organisation Lancaster University
Department Department of Psychology
Country United Kingdom 
Sector Academic/University 
PI Contribution The collaboration includes Dr Trevor Crawford (Department of Psychology, Faculty of Science and Technology), Prof David Allsop (Division of Biomedical and Life Sciences, Faculty of Health and Medicine) and Prof Hedley Emsley (Lancaster Medical School, Faculty of Health and Medicine). Stefanovska and members of her group provided technical expertise in Physics of Dementia and conducted pilot studies for new proposals.
Collaborator Contribution Dr Trevor Crawford and his collaborators helped with recruitment of dementia patients. Each of the partners contributed different scientific aspects to the problem of detecting and treatment of dementia and in writing new proposals. Provided a scholarship for a joint PhD student Juliene Bjerkan, who started in October 2019.
Impact Too early.
Start Year 2017
 
Description Dementia collaboration in Ljubljana 
Organisation University of Ljubljana
Department University Medical Centre Ljubljana
Country Slovenia 
Sector Hospitals 
PI Contribution Aneta Stefanovska established the connection with the Ljubljana dementia experts, including Dr Jan Kobal, who is in charge of Huntington's patients in Slovenia, Dr Bernard Meglic, who is an expert on autonomous systems, and Franci Benko, a research nurse in the Neurology Clinic. With her research team Stefanovska prepared the necessary signal analysis methods for data recorded from patients and healthy controls. Sanja Šešok conducted psychological tests on patients with Huntington disease.
Collaborator Contribution Dr Jan Kobal, who is in charge of Huntington's patients in Slovenia, recruited around 50 patients for measurements, Dr Bernard Meglic recruited around 50 Alzheimer's patients and Franci Benko recruited 50 healthy control subjects and together with Dr Gemma Lancaster from the Lancaster group was in charge of measurement that were completed in June 2018.
Impact Measurements completed. Data analysis in progress. This is a highly multidisciplinary collaboration involving Physics, Biomedical Engineering, Neurology and Physiology.
Start Year 2017
 
Description Edgar Knobloch 
Organisation Stanford University
Country United States 
Sector Academic/University 
PI Contribution We introduced Prof Knoboch to the problems of time-varying dynamical systems with examples from living systems and rogue waves. The Faculty of Science and Techology provided about £5000 to cover his travel and living expenses.
Collaborator Contribution Edgard liaised usefully with all the members of the Nonlinear and Biomedical Physics group and gave them the benefit of his experience and advice, in particular in the field of nonautonomous dynamics and nonlinear fluid dynamics, in which he is a world leading expert.
Impact Prof Knoboch gave a colloquium on 24 May 2018 on "Spatially Localized Structures: Experiments, Theory, Numerics" to a wide audience from the Physics Department.
Start Year 2018
 
Description Marcin 
Organisation Medical University of Gdansk
Department Department of Radiology Informatics and Statistics
Country Poland 
Sector Hospitals 
PI Contribution Helped the collaborator to investigate the relationship between blood pressure and pial artery pulsation oscillations in human.
Collaborator Contribution The collaboration comes from a group that has developed a new device for non-invasive measurements of intracranial flow (NIRT). They are contributing signals that when analysed by our methods promise great impact.
Impact Human subarachnoid space width oscillations in the resting state Gruszecki, M., Lancaster, G., Stefanovska, A., Neary, J. P., Dech, R. T., Guminski, W., Frydrychowski, A. F., Kot, J. & Winklewski, P. J., 15/02/2018, In : Scientific Reports. 8, 10 p., 3057. This collaboration is highly multi-disciplinary, including Physics, Biomedical Physics, Medicine and Engineering.
Start Year 2015
 
Description Nigel Osborne, Ruaraidh Osborne and Ulysis Theatre, Croatia 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution In collaboration with Nigel Osborne and Jozef Stefan Institute cardiac and respiratory signals were recorded from 8 actresses playing "The Bacchae" in the Ulysses Theatre in Zagreb, Croatia in May 2018. The phases were then extracted and sonified. Based on this music was composed and used in the play. In December 2019 another project was conducted in collaboration with Nigel Osborne and Ruaraidh Osborne. Two pianists performed music simultaneously and their cardiac, respiratory and EEG signals were measured in Lancaster. The idea is to investigate inter-subject coherence and synchronization mediated by performance of music. It addresses the question of whether it is possible for two (or more) subjects to display entertainment of their physiological rhythms caused by external perturbation.
Collaborator Contribution The partners proposed the collaboration and helped to bring it about.
Impact The play "The Bacchae" used the 'music', obtained by sonification made in Lancaster, in their performances on 28th, 29th, and 30th July 2018, 1st and 2nd August 2019, and the 17th, 18th and 20th July 2019 in Brijuni, Croatia; and in the ZKM Theatre, Zagreb, on the 17th, 18th, 19th and 20th January 2019,10th May 2019, and 2nd June 2019. Audiences to summer 2019 total about 7000.
Start Year 2018
 
Description Pavle Boskoski 
Organisation Institute Josef Stefan
Country Slovenia 
Sector Academic/University 
PI Contribution My research team and myself introduced to Dr Pavel Boskoski our novel theory of nonlinear, nonautonomous systems and time series analysis methods to investigate their properties from numerical data - either numerically generated or obtained from measurements. Pavle become familiar with our toolbox MODA.
Collaborator Contribution Pavle contributed algorithms for the wavelet transform in Python for the toolbox PyMODA, which is now available on https://github.com/luphysics/MODA. The toolbox MODA and its Python version PyMODA are being prepared for the analysis of dementia data quite generally. He also provided analysis with various methods, both from statistical physics, and nonlinear, nonautonomous dynamics of recordings of beehive weights over time, taken as an example, A manuscript is now in preparation.
Impact A manuscript has been drafted.
Start Year 2019
 
Description Tomislav Stankovski 
Organisation Saints Cyril and Methodius University of Skopje
Country Macedonia, the Former Yugoslav Republic of 
Sector Academic/University 
PI Contribution Aneta Stefanovska and Peter McClintock were PhD and PostDoc supervisors of Dr Tomislav Stankovski. During his stay in Lancaster (2008-2014) Tomislav mastered time series analysis methods and in particular Dynamical Bayesian inference.
Collaborator Contribution Dr Tomislav Stankovski expanded Dynamical Bayesian inference method to include multi-coupling analysis in collaboration with Valentina Ticcinelli, a PhD student funded by Physics Department to work on the project, who coded the algorithm. The method is very relevant for the data recorded during the study.
Impact Dr Tomislav Stankovski co-authored 5 journal papers relevant for our collaborative projects 1. G Nadzinski, M Dobrevski, C Anderson, PVE McClintock, A Stefanovska, M Stankovski, T Stankovski, Experimental Realization of the Coupling Function Secure Communications Protocol and Analysis of Its Noise Robustness, IEEE Transactions on Information Forensics and Security 13 (10), 2591-2601, 2018 2. T Stankovski, T Pereira, PVE McClintock, A Stefanovska, Coupling functions: universal insights into dynamical interaction mechanisms, Reviews of Modern Physics 89 (4), 045001, 2017 3. V Ticcinelli, T Stankovski, D Iatsenko, A Bernjak, AE Bradbury, AR Gallagher, P Clarkson, PVE McClintock, Aneta StefanovskaCoherence and coupling functions reveal microvascular impairment in treated hypertension, Frontiers in physiology 8, 749, 2017 4. T Stankovski, V Ticcinelli, PVE McClintock, A Stefanovska, Neural cross-frequency coupling functions, Frontiers in systems neuroscience 11, 33, 2017 5. T Stankovski, V Ticcinelli, PVE McClintock, A Stefanovska, Coupling functions in networks of oscillators, New Journal of Physics 17 (3), 035002, 2017 and a patent application T Stankovski, A Stefanovska, RJ Young, PVE McClintock, Encoding data using dynamic system coupling, US Patent App. 14/910,547, 2016.
Start Year 2014
 
Title MODA 
Description MODA is a toolbox that provides a set of methods to deal with signals affected by time variability. Currently, it contains 5 methods, including wavlet analysis, wavelet-based phase coherence analysis, wavelet-based bispectral analysis, ridge-extraction and coupling function analysis. It is intended to be very user friendly to be used by the wider scientific community. From June 2019 until now (March 2020) MODA has been updated in two ways - 1. The Matlab version was expanded from 5 to 6 methods, and wavelet phase coherence section was also expanded, so it now consists of: i) Windowed Fourier transform and wavelet transform for time-frequency analysis; individual signals can be analyses, and also power/amplitude can be compared for groups of subject; for example before and after treatment ii) Detection of high harmonics of time-varying oscillations (added in 2020) iii) Wavelet phase coherence and phase shift (added in 2019/20), and evaluation of phase coherence for group of subjects (e.g. before and after treatment); added in 2020. iv) Ridge extraction v) Wavelet bispectral analysis, and vi) Calculation of coupling functions using the dynamical Bayesian inference method 2. All above listed algorithms are being made available also in Python 
Type Of Technology Software 
Year Produced 2018 
Impact Undergraduate and PhD students working with the Nonlinear and Biomedical Physics Group are using MODA; there is also e-mail evidence of extensive use by external researchers worldwide 
URL https://github.com/luphysics/MODA
 
Title PyMODA v0.1.0 
Description PyMODA is a Python implementation of MODA, a numerical toolbox developed by the Nonlinear & Biomedical Physics group at Lancaster University for analysing real-life time-series. Algorithms developed by members of: Nonlinear and Biomedical Physics Group, Physics Department, Lancaster University, UK from 2006 until present. Nonlinear Dynamics and Synergetic Group at the Faculty of Electrical Engineering, University of Ljubljana, Slovenia from 1996 to 2006. Aneta Stefanosvka extends her personal thanks to Aleš Založnik, and to her PhD students. 
Type Of Technology Software 
Year Produced 2020 
Open Source License? Yes  
Impact Other researchers are using MODA. 
URL https://zenodo.org/record/3679258
 
Title Toolbox with surrogate methods for testing dynamical hypotheses 
Description A toolbox that comprises most of the existing surrogate methods to test dynamical hypothesis, such as existence of oscillations, nonlinearities, coherence and coupling. 
Type Of Technology Software 
Year Produced 2017 
Impact The created library of surrogate techniques is used to test for significance of ageing effects. 
 
Description Biological Oscillations conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Stefanovska and her group organised the 9th conference of the European Study Group on Cardiovascular Oscillations which took place in Lancaster from 10th to 14th April 2016. This was also the first International Conference on Biological Oscillations.
The aim of the conference was to provide an interdisciplinary forum for discussions of biological oscillations between researchers drawn from areas such as physics, mathematics, engineering, computer science, cardiovascular regulation, neuroscience, time-series analysis, theory of nonlinear oscillatory dynamics, information processing, cardiovascular and microvascular physiology, cell biology and clinical sciences.
In addition to the signal processing view of cardiovascular oscillations this conference expanded to incorporate a more physics-based approach. It also generalized the topic to include all biological oscillations.
Year(s) Of Engagement Activity 2016
URL http://www.physics.lancs.ac.uk/ESGCO2016/
 
Description Contribution to Headstart Programme 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 30 Y12 Physics students from across the UK participated in the Headstart course. All students are studying A level Physics and another science in many cases and Mathematics and are high ability as indicated by their teachers. Our group organised a whole day event for the students and provided three workshop sessions: Physics of the Brain, Physics of the Cardiovascular System and Physics of the Cell. After a few introductory talks by members of the group students did either measurements or simulations, analysed their data and then presented the results to their audience.
Year(s) Of Engagement Activity 2017
URL http://www.etrust.org.uk/headstart/whatisheadstart
 
Description DSI Wednesday Lunchtime Talk on "Capturing dynamics based on data from non-autonomous, open systems" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact DSI Wednesday Lunchtime Talks, Lancaster University
Calendar entry: 10th March, 12:30-1.30pm
Speaker: Professor Aneta Stefanovska
Title: Capturing dynamics based on data from non-autonomous, open systems
Abstract: DNA in the human body stores more data than the entire world's digital storage capacity. But more importantly, the information is continuously being produced in a dynamical way within our body, which continuously produces ATP - the energy currency of our body - an equivalent to the whole body weight in a single day. Yet, can we decipher this wealth of information in and around us in a unique way, and make sense of it? Is it deterministic, or just random? Although Erwin Schrodinger, one of the fathers of quantum physics, argued that the living systems can be understood only within the framework of open systems, a theory of open systems is still missing. They are continuously exchanging energy and matter with the environment, and are usually complex and nonlinear. Mathematically, they are non-autonomous, and cannot be studied within the framework of an asymptotic approach. They are usually treated as stochastic, and the data they produce are analysed using probabilistic methods. Either mathematical or thermodynamic probability measures are being used to evaluate the amount of entropy they produce. In recent years, such data have been analysed with an artificial intelligence approach based on machine learning methods. In this talk I will present an alternative framework. A finite-time approach will be introduced to study the non autonomous dynamics of high-dimensional systems whose parameters are time-varying. Its potential for extracting the causal relationships that govern such systems will be illustrated, using examples from physical and living systems, and its difficulties and limitations will also be discussed.
Also co-organised
DSI Data Dynamics Lunchtime mini-talks
Calendar entry: 11th March, 12-1.30pm
Speakers: Professor Peter Young - Chris Arridge - Nick Chappell & Wlodek Tych
Year(s) Of Engagement Activity 2021
 
Description Data Science Institute workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Data Science Institute organized a Streaming Data workshop that was held in the Low Wood hotel 18-19 July 2016. I presented our work and participated in many activities of the workshop.The workshop was used to

• explore current Streaming Data research activities at Lancaster;
• identify challenges which can draw mutual interest;
• and develop ideas for future research and funding opportunities in this area.
Year(s) Of Engagement Activity 2016
 
Description Health Innovation talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Talk on "Biological clocks and dynamical health", in the Health Innovation: Digital speaker series, Lancaster University, 28/03/2019
Year(s) Of Engagement Activity 2019
 
Description Physics Department Colloquium, Royal Holloway, University of London, 18 May, 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Delivered a talk "Understanding systems operating far from equilibrium from the perspective of time-varying dynamics" and enjoyed vigorous discussion about differences in living and non-living systems dynamics.
Year(s) Of Engagement Activity 2018
 
Description Physics Master Class: Waves and Oscillations featuring Biomedical Physics Research 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 12 A-level students attended a whole day event which consisted of an introductory talk, two biomedical research taster projects and an oscillations and waves lab to complement their A-level studies. Students prepared group presentations and presented the results of their work. Several feedback - both from students and their A-level teachers indicate that students greatly enjoyed the day and developed an interest in the field.
Year(s) Of Engagement Activity 2017
 
Description Public Lecture (Auckland) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Public lecture on "Biological clocks - adjustable time-keeping makes for good health", in the series Fascination Science, at Massey University, Auckland, on 12/03/2019.
Year(s) Of Engagement Activity 2019
URL https://www.massey.ac.nz/massey/about-massey/events/the-fascination-of-science/the-fascination-of-sc...
 
Description Seminar (Adelaide) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Requests for further information
Year(s) Of Engagement Activity 2019
 
Description Seminar (BLS, Lancaster University) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact "Are biological fluctuations beneficial and can physics help explain them?", Biomedical and Life Sciences Divisional Seminar Programme, Lancaster University, 22/5/2019
Year(s) Of Engagement Activity 2019
 
Description Seminar (Reading) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact Talk at the School of Biological Sciences Research Seminar Series, University of Reading, 16 October, 2018 to students of Biomedical Sciences and Biomedical Engineering and their lecturers interested in the filed of Biological Oscillators. Discussed examples related to ageing, dementia, ASD and the cell, cardiovascular system and brain oscillatory dynamics.
Year(s) Of Engagement Activity 2018
URL https://www.reading.ac.uk/biologicalsciences/SchoolofBiologicalSciences/Research/sbs-research-semina...
 
Description Seminar (York) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Gave a general seminar to a broad audience on "Can science cope with open systems?", which was followed by questions and discussions. Several members of the audience asked for links and reprints.
Year(s) Of Engagement Activity 2019
URL https://www.york.ac.uk/physics/news/events/groups/condensed-matter/14-june-2019/
 
Description Talk at the Teacher CPD events 2020-2021 on "Statistical physics and life - The data driven approach" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Around 20-25 A-level teachers of Physics attended the talk, which was part of a whole-day proggrammue on the Teacher CPD events 2020-2021 at Lancaster University Physics Department on Biology and Physics. The event was organised by Phil Furneaux BSc, MA, Cert Ed, MInstP Honorary Teaching Fellow at Lancaster University and Physics Network Coordinator of the Institute of Physics Cumbria, with the aim to bring to attention to A-level Physics teacher what kind of Physics is useful for tackling problims from Biology and Life Science in general. The event took place on 1st February 2021 on Teams.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=v9B7s_i73oY
 
Description Talk on "Methods to detect deterministic features of `panta rhei'" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact The talk was part of D2I Research Seminars, School of IT Research Seminar Series, Deakin University, on16 October 2020.
Year(s) Of Engagement Activity 2020
 
Description Talk on "Ways of coping with open systems" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact The talk was organised by Prof Cristina Masolleir from the Nonlinear Dynamics, Nonlinear Optics and Lasers (DONLL) Research Group in Physics Department at the Universitat Politecnica de Catalunya. It took place on the 28 February, and initiated discussion in which considerable appreciation of our approach was expressed.
Year(s) Of Engagement Activity 2020