Professor Chrystalina Antoniades of the Nuffield Department of Clinical Neurosciences explains how the COVID pandemic accelerated an innovation in one research project into Parkinson's Disease.
Parkinson’s is a progressive neurological condition, which affects around 145,000 people in the UK.
Symptoms start to appear when there isn’t enough of the chemical dopamine in the brain to control movement properly. People with Parkinson’s don’t have enough dopamine because some of the nerve cells that make it have died.
There are lots of symptoms, but the three main ones are tremor (shaking), slowness of movement, and rigidity (muscle stiffness).
Doctors typically diagnose and monitor the progression of Parkinson’s by assessing these symptoms using a ‘clinical rating scale’. This relies solely on the clinician’s own subjective impression of the person’s condition.
Since 2016, the NeuroMetrology Lab at the University of Oxford has been developing objective numerical measures to help doctors accurately diagnose disease and monitor the progression of Parkinson’s – which could lead to the provision of more targeted and timely treatment. Until recently this research team, based in the Nuffield Department of Clinical Neurosciences, has been carrying out their research via in-person clinics, attended by patients four times a year.
During the patient’s two-hour clinic visit, the researchers would measure subtle abnormalities in the speed and coordination of fast eye movements (known as saccades), hand movements, and gait. They would also assess cognitive performance using tasks on a tablet. Then they would try to work out whether these numerical measures could accurately and objectively quantify Parkinson’s, and track its progression over time.
The advent of home monitoring
One of the features of Parkinson’s symptoms is that they fluctuate both throughout the day and from day to day. So the research team always knew that they wanted to be able to monitor symptoms at home as well as in the clinic. They were aware that patients’ behaviour during short clinic visits every few months was probably not representative of the condition’s progression overall.
In 2020, the Covid pandemic put an immediate stop to research with human participants, making in-person clinics impossible. This apparent disaster in fact accelerated the researchers’ plans to roll out wearable technology and enable study participants to monitor their symptoms at home.
The biopharmaceutical company MSD is funding this new phase of the research project. The new grant has enabled the team, which I am leading, to work with MSD and the technology company Clinical Ink to capture data on participants’ symptoms at home. The wearable technology combines an Apple watch and phone to test a range of both motor and cognitive aspects of Parkinson’s.
I am delighted to be able to offer to our research patients the opportunity to be monitored so closely by such clever technology. My team has been working hard to make this a pleasant experience for all our patients and we are incredibly honoured to have such tremendous support from the Parkinson’s Disease community.
‘Digital health technologies offer tremendous opportunity to measure and objectively quantify the symptoms and progression of neurological disease,’ said Dr Marissa Dockendorf, Executive Director, Head of Global Digital Analytics and Technologies at Merck’s MSD Research Laboratories. ‘MSD is excited to collaborate with the University of Oxford on this Technology and Analytics study to further the development and characterisation of digital measures to support timely and reliable evaluation of potential new treatments for Parkinson's disease.’
How patients can monitor their symptoms at home
A member of the team sets everything up with participants remotely during a telemedicine appointment, explaining how to use the watch and the app on the phone. The participants receive instructions and the app gives step by step guidance on what to do. Participants are required to carry out testing at home once a month, performing tasks on the app such as reading, testing reaction times, and cognitive tasks.
David Williams, a participant in the study, said: ‘The wearable technology is very easy and comfortable to use. The instructions are very clear, the exercises are well explained and not at all difficult to accomplish. The staff are friendly, approachable people who always leave me with a sense of being valued as a contributor to what is obviously a very important research study. If you’re at all anxious about taking part, don’t be, just sign up. You won’t regret it!’
Kevin McFarthing, another participant, also stressed how easy it was to carry out home monitoring: ‘The OxQUIP team is very professional and thoroughly well organised, and are a pleasure to work with. They did a great job training me to use the remote devices’, he said.
The home monitoring does not replace clinic visits entirely; patients have a telemedicine appointment every four months, as well as the opportunity to come in to an in-person clinic if they wish.
Joan Severson, Chief Innovation Officer at Clinical Ink, said: ‘We are honored that our mobile and wearable technology plays an integral role in this study of Parkinson’s disease in Oxford. We are excited to collaborate with researchers who tirelessly work to increase objective numerical measures for diagnosing and monitoring disease progression.’
Looking to the future
The Covid pandemic was a dark period for many, and yet it accelerated this change in the way this research project is being carried out. The team is now able to gather richer, more nuanced and accurate data to feed into their analysis.
The outcomes of this project will improve the diagnosis, tracking and treatment of Parkinson’s. The insights gained about monitoring disease progression will make the assessment of clinical trials more efficient, leading to faster drug discovery not only for Parkinson’s, but potentially for a range of neurological conditions.
This work is part of the OxQUIP (Oxford Quantification in Parkinsonism) programme. If you’re interested in taking part in this study, please email Oxquip@ndcn.ox.ac.uk.
Professor Paul Riley, Director of the Institute of Developmental and Regenerative Medicine discusses how better-designed research buildings can help scientists break out of their silos.
The advances made in medical and biological sciences within our lifetime are staggering. It seems strange to think that the project to sequence the human genome took over a decade to complete back in 2001, yet similar sequencing technology is now portable and is used daily in the field.
Each advance in research has opened up new avenues of exploration and with each new stride whole new research disciplines have emerged. Sadly, in modern science it is impossible to be an expert in more than a few things, despite the fact that most scientists will have chosen their careers early on because of a fascination with all things to do with science, and a desire to keep learning and making new discoveries themselves.
Yet we are increasingly finding, in areas such as our response to pandemics or cancer treatments, it is vitally important that these related avenues of research should remain in contact with one another. The discovery of a new technique in one area could be just as useful to another, and research into complex medical issues is increasingly becoming multi-disciplinary.
Some years ago we began to plan a way of creating a new type of working environment for researchers, which could encourage scientists to mingle more with people from outside their own niche discipline. The logic is simple – scientists are passionate about their work and love talking about it. But the problem with many labs is that most researchers find themselves surrounded only by others from their own field and much of what is going on elsewhere is behind closed doors.
This was the idea behind the Institute of Developmental and Regenerative Medicine (IDRM) – to bring the related disciplines of cardiovascular science, immunology and neuroscience together under one roof, and to design it in a way that increases the chances of these groups mixing socially and professionally, promoting conversations to stimulate new ideas and collaborations between students, post-docs and PIs.
The newly-opened IMS-Tetsuya Nakamura Building is the home for the IDRM, and has been designed around shared common and break-out spaces which differ across each floor in flavour thus linking the laboratories and offices within each discipline vertically to promote mixing and collaboration from the ground-up.
My own research in cardiovascular science involves regular collaboration with colleagues in neuroscience and immunology, who I will now have on my doorstep, and who I can see coming and going each day. Georg Holländer’s group work on how immune cells learn ‘self’ from ‘non-self’ during development. Following a heart attack release of certain proteins from damaged heart muscle triggers a ‘non-self’ reaction, worsening the outcome and promoting heart failure. We can now work together to ask broad questions as to how cells identify ‘self’ and how can we intervene to ensure the body’s own immune response does not react badly during a heart attack. Each experiment and subsequent discovery can be discussed with the immunologists on the floor above in our breakout space.
The siting of the IDRM was also designed to put the researchers at the heart of the science and technology cluster in the Old Road Campus, and between the Headington hospitals where many researchers also work. For example, combining state-of-the-art imaging facilities across the road in the Kennedy Institute with newly purchased microscopes in the IDRM into a new Centre of Excellence will be a powerful tool for many researchers across both institutes and the wider campus.
But the drive to improve cross-disciplinary collaboration goes far beyond just the new building. We are working to improve our links to disciplines within maths to model disease, and the social sciences, such as law and ethics, which will have a major role in shaping and guiding research, as well as collaborations with industry on site, such as Novo Nordisk, and the BioEscalator facility to help turn new research into successful spinout companies that can develop real-world applications.
How effectively we manage to our cross-disciplinary collaborations will play a large part in the speed and efficiency of future research and development and the delivery our findings into clinical care but it will also make a career in science even more engaging.
Her Majesty the Queen is the first British monarch to celebrate a Platinum Jubilee, but Royal Jubilees have been celebrated for hundreds of years – complete with military parades, porcelain memorabilia, special coins and much popular enthusiasm. The excitement and pageantry around Queen Victoria’s Diamond Jubilee is well known and preserved in early film and photographs. But a Golden Jubilee was first celebrated by a British king, Edward III, in the 12th century, and Victoria’s grandfather, George III, was acclaimed some 200 years’ ago, for his 50 year reign – in spite of early unpopularity, growing radicalism and debilitating mental illness.
George III. Reign 1760-1820
George III is best known for this long illness and for ‘losing’ the American colonies. But the pattern and many of the traditions around the monarchy and in terms of royal jubilees began in his reign and the monarch came to be seen popularly as synonymous with Britain.
Despite this, however, the Hanoverian king eventually came to be associated with patriotism and the essence of Britishness. This, perhaps, began with his person. Most scholars now would say he made poor choices initially, but not many doubt his sincerity and they recognise he took his duties very seriously. He was not a spendthrift and he was a devoted family man and the image started to change.
Edward III. Reign 1327-1377
On 28 January 1377, Adam Houghton, bishop of St David's, addressed the English parliament in the Painted Chamber at Westminster. He told the assembled lords and commons that Edward III had now occupied the English throne for over 50 years, and thus announced the end of Edward’s ‘jubilee year or year of grace’.
The English government had been determined to celebrate Edward’s jubilee year with a series of public spectacles. First, the king presided over a week-long tournament held at Smithfield in February 1376. Second, he played his part in a meeting of the Order of the Garter at Windsor Castle in April 1376. But thereafter the festivities fizzled out. A further tournament that had been planned to take place at Smithfield in June was cancelled. The remainder of Edward’s jubilee year was dominated by the political fallout from the explosive ‘Good Parliament’, which lasted from April to July; the sorrow which met the death of the king’s first-born son – the Black Prince – on 8 June; and the king’s own failing health.
Nonetheless, there were some muted celebrations to mark the day of Edward’s jubilee itself, which fell on 25 January 1377. According to the Anonimalle Chronicle, ‘the commons of London made great entertainment and celebration’, culminating in a show before the Prince of Wales and other members of the nobility in Kennington. However, there are no signs that either the royal court or other towns and cities did much to mark the occasion. Indeed, one man was conspicuously absent from both the celebrations in London and the parliament which opened two days later: the king himself. Edward III was confined to his quarters at his manor of Havering in Essex, and was too unwell to travel; as Houghton explained, he had been laid low and ‘in great peril of his life’. When he finally left Havering the following month, to move to his manor of Sheen in Surrey, a chronicler reported that he made the journey with ‘great frailty’. While the cause of Edward’s ill-health is unclear – although it is likely that he suffered from a series of debilitating strokes – he did not recover, and died on 21 June 1377, at the age of sixty-four.
Although Edward’s infirmity cast a shadow over the last years of his reign, it should not blind us to what he achieved during his fifty years on the throne. When Edward was crowned in 1327, the English monarchy had been in the midst of an unprecedented crisis. His father, Edward II, aroused discontent, distrust, and anger because of his regime’s harsh and heavy-handed treatment of political society; his government’s military failures against both France and Scotland; and his own scandalous relationship with his favourites, Piers Gaveston and Hugh Despenser the Younger. This led to Edward II being overthrown in the first deposition of an English king since the Norman Conquest. Yet over the course of his reign, Edward III rebuilt the monarchy’s prestige and reputation, restored the crown’s relationship with the aristocracy, and revived England’s military fortunes, with English forces triumphing over their French foes at the Battles of Crecy and Poitiers in 1346 and 1356 respectively.
The response to Edward’s death suggests that his subjects appreciated his accomplishments and longevity. The chronicler, Jean Froissart, remarked that his death was ‘to the deep distress of the whole realm of England, for he had been a good king for them’, and described how his funerary procession was observed by mourning crowds. Other commentators also heaped praise on the departed king; Thomas Walsingham, a monk of St Albans, later wrote that ‘among all the world’s kings and princes, he [Edward] had been a glorious king, benevolent, merciful, and magnificent’. But perhaps the most remarkable tribute to the king is the inscription that runs around the perimeter of his tomb:
‘Here is the glory of the English, the paragon of past kings,
The model of future kings, a merciful king, the peace of the peoples,
Edward the Third, fulfilling the jubilee of his reign.
The unconquered leopard, he was a powerful Maccabeus in his wars.
While he lived prosperously, he restored to life his kingdom in probity.
He ruled mightily in arms; now in heaven may he be heavenly king’.
By Sam Lane
The mental illness which affected him was partly responsible for George III’s rehabilitation. He was seen sympathetically as a ‘King Lear-like figure’. And, in a defining 1984 article about George III , Princeton Professor Linda Colley says, ‘After 1789, prints portrayed him regularly as St. George, as John Bull and, after his mental collapse in 1810, as a wise, Lear-like patriarch and the celestial guardian of his nation.’
As well as increasing personal sympathy for ‘Farmer George’, the monarchy became the symbol of Britishness to counter the forces of autocracy that were seen on the Continent.
A mark of the considerable change in mood during his reign, was the reaction to his death in 1820. Some 30,000 people gathered for the funeral, although he had been unwell for the last decade, it was described as ‘if the paternal roof had fallen in, and left our chambers desolate’. Shops across England, Scotland and Wales closed.
Although such marks of respect might be expected now, that had not been the case in the early part of George III’s reign – or in respect of his immediate predecessors. Since Charles II, the monarchy had not enjoyed unalloyed popularity, especially with radical politics gaining ground.
According to Professor Colley’s article, ‘Ever since the passing of that immediate euphoria which greeted the Restoration, no English or British monarch other than perhaps Anne had achieved more than partial or transient popularity; no sovereign at all had been able to act as an unquestioned cynosure for national sentiment.’
So much had changed, though, that when George celebrated the beginning of his 50th year of kingship on 25 October 1809 – the first Golden Jubilee in 500 years. Lord Palmerston said, ‘Nothing could be better than its effect in London.'
In the course of George III’s reign, the view of the monarchy had changed. The main national anthem became ‘God save the King’, supplanting Rule Britannia. The State Coach was built, which was used at Her Majesty the Queen’s Coronation and will feature in this year's Platinum Jubilee procession. And a new focus on the monarch was used to distinguish patriotic British celebrations from those in revolutionary France.
Not all were convinced, as Professor Colley pointed out, Sir Francis Burdett claimed in the House of Commons that George Ill's jubilee was a "clumsy trick, to thrust joy down the throats of the people", in the wake of soaring food prices and other misfortunes.
But celebrations took place around the country and these were not always organised officially, with Napoleon in mind. Local authorities and individuals organised and led events nationally. And the Press was key in encouraging support, although what would today be called liberal elites criticised the celebrations.
According to Professor Colley, however, ‘The sheer scale of this event was a remarkable tribute to the activism of the press and, it would seem to public opinion which compelled many local authorities into action.’
At the same time, some of the other familiar activities around royal events developed - a thriving souvenir trade was established, Jubilee good works were encouraged, great crowds gathered to celebrate and sermons were preached.
During his reign, George III gradually became more popular in his own right. But the French Revolution, and the execution of the French monarch, would serve to cement his position as the father of the nation. These firmly established the British monarchy as the rallying point for patriotism - in contrast to the Revolutionary events in France and Napoleon’s 'adventures' across the Continent.
There were very real invasion scares in the early 1800s and the traditional Anglo-French rivalry came to be seen differently. By the time of his Golden Jubilee in 1809, the safety of the state was associated with the safety of the King.
With thanks to Dr Perry Gauci
 Professor Linda Colley: The Apotheosis of George III: Loyalty, Royalty and the British Nation 1760-1820. Pages 94-129 Past & Present, volume 102, Issue 1, February 1984.
Putting objects online is not just a nice-to-have, the Ashmolean’s curators insist, (although it is that). Digitisation is going to transform scholarship, adds Richard Ovenden, the head of Oxford’s Galleries, Libraries and Museums and the 25th incumbent as Bodley’s Librarian.
Digitisation is revolutionising research...Digitisation makes ‘big data’ research possible in the Humanities
Professor Chris Howgego
In terms of money, in particular, the implications could be far-reaching, Professor Howgego says. Not only will it will allow access to currently unseen objects – but more importantly it will also raise new questions and enable new methodologies, throwing a different light on past civilisations and societies, he explains.
With international collections and coin finds being put online, it will be possible for researchers to look in new ways at patterns of behaviour in the past and to work with other institutions to gain a much greater understanding of the ancient world. He says, ‘Digitisation makes ‘big data’ research possible in the Humanities.’
Although much focus on ancient coins comes from newspaper reports of sums raised, when finds are sold at auction, money provides a window into earlier cultures and societies. Professor Howgego’s enthusiasm for the subject is palpable.
If it were needed, the Ashmolean Museum’s 300,000 piece historic monetary collection, is proof positive that you cannot take it with you. It contains items from around the world, which have survived their owners by hundreds, if not thousands, of year. Made up of medals, bank notes and coins (some dating back to before 600 BC) the collection includes original Ming dynasty paper money, and some of the earliest coins ever minted, as well as golden hoards, buried in Oxfordshire, whose owners never returned to claim them.
It's history in your hand
The Ashmolean Museum’s 300,000 piece historic monetary collection is proof you cannot take it with you. It contains items from around the world, which have survived their owners by hundreds, if not thousands, of year
As crypto currencies around the world take a slide, leading many to question what is money, the Ashmolean team is in no doubt of the importance of the collection of which they are custodians.
‘It’s history in your hand,’ says Professor Howgego, of a coronation medal made for the accession of the boy King, Edward VI – and of a Roman gold coin thought to have been minted from gold looted from the Temple in Jerusalem.
Clearly proud of the collection and the research taking place in Oxford, Professor Howgego reveals there has been a new (2,000-year-old) acquisition for the Ashmolean. It is an unparalleled collection of 1085 gold and silver coins of the Iceni (Boudicca’s tribe): some of these tiny, impossibly brilliant coins, astonishing survivors from late Iron-Age Britain are in a special display in the Money Gallery, shining two millennia after its owners were dead and buried. And these are just a fraction of the historic coins on display and in the Museum’s secure vault behind the scenes.
Oxford’s Ashmolean, the oldest public museum in the world, is home to one of the world’s leading collections of ancient money. It is a resource for academics and experts, increasingly globally, now the collection is being made available online.
Of the 300,000 items, a third have already been digitised, thanks to the efforts of volunteers in Oxford
Dr Jerome Mairat
The Ashmolean’s collection may be worth a fortune but, says curator Dr Shailendra Bhandare, its real value is as a record of the past. He explains, money has been made of metal, stone, shells, cloth and even rice – whatever is of value to the society. And the coins and notes tell much about the societies which created them, the development of the civilisations and trade – and war.
One of the ‘highlights of the collection, is the Oxford crown, struck during the English Civil War, in Oxford’s brief time as Charles I’s capital city. There are only about ten in existence, and two are in the Ashmolean. They were made in a mint in New Inn Hall Street.
Meanwhile, a new Roman emperor was discovered, found in hoard at Chalgrove, only 12 miles away.
‘They were dancing the conga at the British Museum when it was identified,’ recalls Professor Howgego. The curator who discovered it said it was so surprising that ‘It was like flicking through a pack of cards and finding an 11 of clubs.’
The Ashmolean’s collection may be worth a fortune but its real value is as a record of the past
Dr Shailendra Bhandare
The coins themselves were often designed as records, rather than just being of monetary value, says Professor Howgego – used by rulers to put their stamp, quite literally, on history. From the images of short-lived Roman emperors, to pictures of Noah’s Ark, coins have been used to make statements – and not just in terms of the legality of tender.
The Coin Hoards of the Roman Empire Project, based in the Ashmolean, leads a collaborative international effort to preserve digitally this compelling form of national heritage. It has currently put online over 16,000 hoards containing a staggering eight million coins. The Roman coins that turn up today across Europe and Asia reveal the integrated nature of the Roman Empire – and its impact on neighbouring civilisations, such as India, where huge numbers of Roman coins have been found.
You couldn’t buy a loaf of bread with one of the coins...It could be worth a week’s earnings
Professor Andrew Meadows
It is thought the earliest coins were created by rulers to pay soldiers to fight in wars
He says, we already know the first coins emerged in the Greek province of Lydia in what is now Turkey. But the coinage was not then, he explains, about facilitating trade and coins were not used by most people.
‘You couldn’t buy a loaf of bread with one of the coins,’ he says, holding a chunky gold piece. ‘It could be worth a week’s earnings.’
It is thought, he says, coins were created by rulers in order to pay soldiers to fight in wars, rather than to facilitate trade – although they did that as well.
Digitisation of ‘history in your hand’ is set to transform research.
David Kerr, Professor of Cancer Medicine at the Radcliffe Department of Medicine, discusses his research and the importance of international collaboration to support cancer care across Africa.
I have been, and still am, a cancer researcher and practising physician who has developed a sort of side line in health policy support, based on the idea of ‘amplified good’. I see the enormous importance of individual consultation with the patients we see in our clinic, and this is magnified by our research which is carried into clinical practice around the world.
But the benefits of this are eclipsed by the potential population benefits of delivering health policy plans which will have an impact on cancer control for many millions of citizens: the good of an individual consultation is amplified many fold by effective health policy.
My friend Twalib Ngoma and I were Fellows together 35 years ago in Glasgow. I visited his cancer centre all those years ago and found that 80-90% of cancer patients presented with advanced, Stage 4 disease - well beyond the capacity of any healthcare system to offer anything other than palliative care. When we attended clinic together much more recently in Dar es Salaam, nothing had changed – all the patients that we saw carried massive tumour burdens.
Now, in sub-Saharan Africa , urgent action is needed to stem a growing crisis in cancer incidence and mortality. Without interventions, data estimates show a major increase in cancer deaths reaching about 1 million deaths per year by 2030. The growing cancer crisis is attributable to external and internal factors, including infections with viruses, changing population demographics, behavioural changes, environmental exposures, genetics, and weak healthcare systems.
Under the auspices of a Lancet Commission, we have drawn on the wisdom and practical experience of widely acknowledged leaders, representing the spectrum of cancer control, with expertise in prevention, early detection, treatment, education and research to provide a clear set of practical policy recommendations for Sub Saharan African nations.
To some extent, we are cancer lobbyists in that we aim to influence public officials, especially members of legislative bodies and sway public opinion, but we do so from a position of professional expertise, of evidence offered and a profound sense of timeliness. We have seen too many reports, too many words, too many good intentions, too many families torn apart, too many excruciatingly painful deaths to feel that we can brook any further delays in taking collective action to accelerate Sub Saharan African cancer control.
The President of Ghana, Nana Addo Dankwa Akufo-Addo and the President of the House of Chiefs, Ogyeahohoo Yaw Gyebi II preside over the launch of the Commission which calls for the following actions:
- Cross governmental cost effective cancer planning
- Equity by expanding Universal Health Coverage to reduce out of pocket expenditures for essential therapy for citizens with cancer, with a view to avoiding catastrophic bankruptcies and abandonment of treatment
- Invest in cancer registration in order to provide that data upon which rational cancer planning will be undertaken
- pilot early cancer screening and detection programmes which make use of point of care technology
- Gap analysis of existing versus optimal services (staff, equipment, infrastructure) will be undertaken as a main component of the NCCP and a realistic investment plan constructed in 5 year cycles
- Improve access to opiate analgesics, available to less than 10% of African cancer patients, which, again, needs a joined up government response, spanning health, justice, police and finance section
- Education and training will be the mainspring of any cancer plan and has enormous partnership potential – North-South; South-South; public-private; NGO-professional societies-governments
- Research and innovation underpins rational delivery of cancer care. African cancer researchers are keen to contribute to global cancer knowledge and to focus the wider research community on African cancer problems
Let me repeat our call to action and urge politicians, policy makers, healthcare professionals, NGOs, professional societies and citizens to unite and chart a collective (and individual) response to the increasing burden of cancer in Africa. The amplified good of collaborative action to shape the actions of health systems and health policies is vital now, as the prospect of a million deaths every year from cancer looms.
David Kerr is Professor of Cancer Medicine at the Radcliffe Department of Medicine, University of Oxford. He is also a consultant physician within the NHS.
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