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The ‘all hands on deck’ approach to medical device research at Cúram

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Sam Cox shines a spotlight on Cúram, the Science Foundation Ireland research centre developing life-changing medical devices.

Across scientific research, ‘transdisciplinarity’ has become a buzzword. It is no longer enough to remain statically in a single academic area without linking in with your peers and seeing how other systems interact.

This is particularly prominent in medicine. The human body is an interlinked series of systems, organs and mechanisms. Some of these interplays are well-understood. Our interventions for when they go wrong are often straightforward and effective. Other interactions still elude us.

This is what Cúram, the Science Foundation Ireland research centre for medical devices, tries to remedy. Hosted by NUI Galway, their smart medical device technologies aim to find creative solutions to complicated problems.

Life-altering decisions

Take, for instance, diabetes. One of the key problems with type 2 diabetes is hesitancy to take insulin injections. Dislike of needles, stigma around medication for life and fear of the unknown often lead people to delay taking insulin injections, impacting the severity of ultimate health outcomes. It is problems like these that Cúram tackles.

By reimagining delivery systems, such as slow-release tablets for oral ingestion, there is a concentrated effort at making real differences through clever technology. To do this, disciplines as diverse as engineering, materials science, biochemistry, medicine, and social science converge with academics, industry and clinicians. Creating solutions means advancement not only within these sectors, but for medical innovation.

Choosing which solution to pursue is a magnified Sophie’s choice in medicine. Some work is short-term with little doubt of its requirement. During the early stages of the Covid-19 pandemic, researchers were involved in optimising ventilators to allow more patients to be treated with the same number of devices. Other projects are longer-term. In its previous research cycle, the Galway-based Cúram centre was a panoply of cutting-edge ideas and solutions, with 244 separate potentially breakthrough projects on the go. Of these, 16 have been carried forward – those with the most chance of realising life-altering technologies.

To carry these projects out, teams of engineers, clinicians, patients and researchers are assembled. Academics and industry come together. All of these assets are co-ordinated to address specific problems, all with the goal of melding outside systems into the factory of the human body.

Prof Abhay Pandit, director of Cúram, explains that careful criteria were developed, and an external world-renowned board of clinicians, academics and industry was set up to evaluate “How can we get concepts to the patient and what can we do to facilitate that?”

To get to the patient, Cúram needs support from industry, as its ultimate goal is to make technologies widely available. While Cúram deals with a variety of medical ailments, it has divided its next stage of research into three broad domains: soft tissue, musculoskeletal-neural, and renal-cardiovascular-metabolic. But when the crux of the objective is to improve quality of life, how can projects be compared?

What can be compared is what stage the research is at. Pandit describes one project centred around a gel to alleviate pathological symptoms after a heart attack. While this is a blue-sky project that is four to six years from fruition, the studies conducted are very advanced – a metric that puts them at the front for funding.

Moving from project to prototype is the aim of the centre in its next funding phase, and a central motivation for the increased transdisciplinarity. It’s an all hands on deck approach to get results in the immediate future.

The balancing act

In the left atrium of the heart there is a sac called the left atrial appendage. “It has no anatomical function – it’s just an evolutionary hangover,” said Dr Martin O’Halloran, whose research tackles atrial fibrillation.

For some patients, the heart pumps inefficiently and blood gets trapped in this sac. If blood sits, it clots, and can get back into the bloodstream. If it travels to the brain, it can cause a stroke. Currently, patients undergo two open-heart surgeries to fix the problem – three hours to fix the electrical issue and a second three hours to fix the mechanical problem by putting in a plug. O’Halloran and industry partners are working on developing a device that can be implanted alongside the electrical fix to achieve both surgeries in one go, effectively halving the time undergoing high-risk surgery.

Another Cúram project involves using thermal therapy to treat high blood pressure (hypertension). Affecting more than 1bn people worldwide, 12 to 18pc of cases are caused by abnormal hormone-secreting tumours on the adrenal glands. Currently, the most effective cure is to take the gland out with surgery – a solution that works when one gland is affected, but not when it’s both. These patients require a drug that often carries nasty side effects while lacking the same effectiveness. O’Halloran and his team want to burn these tumours off, saving the healthy tissue and solving the problem.

‘This is for societal good, even if the commercial case isn’t fully there yet’
– DR MARTIN O’HALLORAN

After a few years working in academia as an engineer for medical devices, O’Halloran had become frustrated at the lack of research making its way to the clinic.

“I looked at groups nationally and internationally who were developing devices that made it to the clinic and the common denominator was in the groups where the project lead was a clinician, or groups that were physically located in a hospital,” he said.

This spurred the move of his engineering laboratory to the hospital, where the focus is always patient impact.

O’Halloran feels the strength of the Cúram is in allowing industry to come to the research centre with a problem, gaining access to a network of researchers that can tackle every aspect of that problem. Rather than trying to recruit a jack of all trades and master of none, Cúram has created a network where everyone knows the right person to go to. If industry can get access to universities, they get access to resources – and that’s when innovation becomes feasible.

According to O’Halloran, more than 90pc of the research is making incremental changes. It’s very hard to do disruptive research. “If you talk to medtech investors, you want a balanced portfolio. You want some incremental low-risk guaranteed to deliver, but you also want high-risk high-gain. In a way, I think the academic sector needs to do that. In my lab, if we went to a funder with a 10-year project, it’s a big ask to ask for funding. But if you prove yourself through smaller projects, you get a lot of credence and then they trust you on the more ambitious projects,” he said.

“We’re doing a project for blood pressure, and if you were to look at the commercial case, it’s not there yet. Loads of the pieces of the jigsaw are missing, because it is, at best, 10 years to fruition. But I love that, as an academic institution, we can look at that. This is for societal good, even if the commercial case isn’t fully there yet.”

This is where Cúram draws its strengths – not only from the interdisciplinarity of the fields within the centre, but its balance between industry and academia. Having worked in both, O’Halloran talks of the ‘rent-a-brain’ nature of consultancy work and being mined to solve a particular problem. Equally, academia often lacks the funding, or the practical applications needed to realise its conceptual ideas. He is clearly thriving in the balance.

Teaching new postdocs to navigate this borderline isn’t easy. “They’re used to answering questions thoroughly. You don’t give an answer until you know within a certain confidence interval that you’re correct,” said O’Halloran. Industry, on the other hand, wants the best guess at the present moment in time. It is about working on enough information to make the best next decision and having confidence that you will learn more and adjust accordingly as you go on. “Understanding that tension is really important,” added O’Halloran.

With more than 200 researchers trained within Cúram’s first research cycle, and 13 Innovative Training Networks specifically set up for its next phase, the centre is aiming to teach this interdisciplinarity as a language and navigate accordingly.

A blonde woman with wavy hair pictured against a dappled grey background.

Dr Karen Doyle. Image: Cúram/NUI Galway

Getting straight to the heart of the matter

In terms of a worldwide collaboration spanning countries and continents, we look to Dr Karen Doyle, who is at the epicentre of research into the cause of stroke.

Doyle is aiming to understand stroke at the level of composition. Blood clots can cause a blockage in the brain, leading to an ischemic stroke (versus a haemorrhagic stroke, which is caused by a rupture or tear in the blood vessel). Blockages can be caused by clots of all compositions. Yellow ones. Stringy ones. Ones filled with platelets or ones made of mainly red blood cells. Ones that can be removed in one go during a process called a thrombectomy, or ones that take repeated attempts. Some thrombectomies involve putting a stent retriever in and grabbing the clot, while others are sucked out through an aspiration device. There’s even recent evidence that some clots are caused specifically by Covid-19.

While strokes are distressingly common, affecting one in six men and one in five women globally, Doyle highlights how few forms of intervention have existed up until recently. Before the late 1990s, doctors were largely limited to providing care for the patient rather than any treatment. Then a drug called tissue plasminogen activator (tPA) was approved and some clots could be broken down, but only when they are fibrin-based (a tough, non-globular protein found in the blood).

With the advent of better imaging technology, it became increasingly possible to look into the brain and see what was going on in those suffering from strokes. In the mid-2000s, radiologists were able to see the vasculature of the brain and developed stent technology to reach clots. In fact, in 2015, Doyle explained, five seminal studies showed “without a shadow of a doubt” that feeding a medical device through the heart to reach the site of the clot and physically remove it is “hugely beneficial”.

These removed clots are now the samples that Doyle is collecting to build databases of clots in all their shapes and sizes from around the world. “When the clot is removed, we provide formalin pots to the hospital to collect the clot. We then courier the clots to our lab,” said Doyle. “The first thing we do is take a photograph. It’s amazing – even just studying the clots at that level, they look so different.”

After that, the clots are embedded into wax which gives them a stability to cut into thin slices of three micrometres, and tests are performed. Histology is first, where a stain called Martius Scarlet Blue is applied to reveal the microsocopic anatomy of the clot. Next is immunohistochemistry where an antibody is applied to selectively identify antigens in the cells, and in particular to look for the components that are related to aetiology. Finally, they use mass spectrometry to glean whatever further information is possible.

“For the Restore registry, we have Beaumont [Hospital in Dublin], but we also get clots sent to us from Gothenburg in Sweden, Budapest in Hungary and Athens in Greece,” she said. “We’re seeing similar findings to North American clots. However, Japan is an interesting new development. There is evidence that there is difference in an Asian population. Their diet is considerably different.”

Where O’Halloran focused on what Cúram could provide industry partners, Doyle highlights the close relationship with clinicians. In her case, the surgeons and doctors who are removing the clots and sending them samples. With more than 1,000 patients sampled, her team hopes to provide the groundwork that will eventually lead to industry design and, more immediately, a clinical understanding for their procedural approach. While they have industry partners, their publications and conference speakers make their discoveries known to all in the scientific community.

Doyle hammers home what Pandit had also made clear: that for all of Cúram’s projects, the central message is ‘we are ready to work with you on this’ and to tie all of the strands together for the sake of the patient.

This is what transdisciplinarity means for Cúram. Realising change for those affected when the interplay of bodily systems goes awry.

By Sam Cox

Sam Cox was named the science and technology winner in the 2020 National Student Media Awards (Smedias). This award category is sponsored by Science Foundation Ireland and includes a €1,000 bursary to support and encourage up-and-coming science and technology journalism.

The 2021 Smedias are now open for entries. The deadline for applications is 15 April 2021.

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Amazon Web Services outage hits sites and apps such as IMDb and Tinder | Amazon

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Several Amazon services – including its website, Prime Video and applications that use Amazon Web Services (AWS) – went down for thousands of users on Tuesday.

Amazon said the outage was probably due to problems related to application programming interface (API), which is a set of protocols for building and integrating application software, Reuters reported.

“We are experiencing API and console issues in the US-East-1 Region,” Amazon said in a report on its service health dashboard, adding that it had identified the cause. By late late afternoon the outage appeared to be partially resolved, with the company saying that it was “working towards full recovery”.

“With the network device issues resolved, we are now working towards recovery of any impaired services,” the company said on the dashboard.

Downdetector showed more than 24,000 incidents of people reporting problems with Amazon. It tracks outages by collating status reports from a number of sources, including user-submitted errors on its platform.

The outage was also affecting delivery operations. Amazon’s warehouse operation use AWS and experienced disruptions, spokesperson Richard Rocha told the Washington Post. A Washington state Amazon driver said his facility had been “at a standstill” since Tuesday morning, CNBC reported.

Other services, including Amazon’s Ring security cameras, mobile banking app Chime and robot vacuum cleaner maker iRobot were also facing difficulties, according to their social media pages.

Ring said it was aware of the issue and working to resolve it. “A major Amazon Web Services (AWS) outage is currently impacting our iRobot Home App,” iRobot said on its website.

Other websites and apps affected include the Internet Movie Database (IMDb), language learning provider Duolingo and dating site Tinder, according to Downdetector.

The outage also affected presale tickets for Adele’s upcoming performances in Las Vegas. “Due to an Amazon Web Services (AWS) outage impacting companies globally, all Adele Verified Fan Presales scheduled for today have been moved to tomorrow to ensure a better experience,” Ticketmaster said on Twitter.

In June, websites including the Guardian, Reddit, Amazon, CNN, PayPal, Spotify, Al Jazeera Media Network and the New York Times were hit by a widespread hour-long outage linked to US-based content delivery network provider Fastly Inc, a smaller rival of AWS.

In July, Amazon experienced a disruption in its online stores service, which lasted for nearly two hours and affected more than 38,000 users.

Users have experienced 27 outages over the past 12 months on Amazon, according to the web tool reviewing website ToolTester.



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South Korea sets reliability standards for Big Tech • The Register

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South Korea’s Ministry of Science and ICT has offered Big Tech some advice on how to make their services suitably resilient, and added an obligation to notify users – in Korean – when they fail.

The guidelines apply to Google, Meta (parent company of Facebook), Netflix, Naver, Kakao and Wavve. All have been told to improve their response to faults by beefing up preemptive error detection and verification systems, and create back up storage systems that enable quick content recovery.

The guidelines offer methods Big Tech can use to measure user loads, then plan accordingly to ensure their services remain available. Uptime requirements are not spelled out.

Big techs is already rather good at resilience. Google literally wrote the book on site reliability engineering.

The guidelines refer to legislation colloquially known as the “Netflix law” which requires major service outages be reported to the Ministry.

That law builds on another enacted in 2020 that made online content service providers responsible for the quality of their streaming services. It was put in place after a number of outages, including one where notifications of the problem were made on the offending company’s social media site – but only in English.

The new regulations follow South Korean telcos’ recent attempts to have platforms that guzzle their bandwidth pay for the privilege. Mobile carrier SK Broadband took legal action in October of this year, demanding Netflix pitch in some cash for the amount of bandwidth that streaming shows – such as Squid Game – consume.

In response, Netflix pointed at its own free content delivery network, Open Connect, which helps carriers to reduce traffic. Netflix then accused SK Broadband of trying to double up on profits by collecting fees from consumers and content providers at the same time.

For the record, Naver and Kakao pay carriers, while Apple TV+ and Disney+ have at the very least given lip service to the idea.

Korea isn’t the only place where telcos have noticed Big Tech taking up more than its fair share of bandwidth. The European Telecommunications Network Operators’ Association (ETNO) published a letter from ten telco CEOs asking that larger platforms “contribute fairly to network costs”. ®

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Twitter acquires Slack competitor Quill to improve its messaging services

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As part of the acquisition, Quill will be shutting down at the end of the week as its team joins the social media company.

Twitter has acquired the messaging platform Quill, seen as a potential competitor to Slack, in order to improve its messaging tools and services.

Quill announced that it will be shutting down at the end of the week as its team joins the social media company to continue its original goal “to make online communication more thoughtful, and more effective, for everyone”.

The purchase of Quill could be linked to Twitter’s new strategy to reduce its reliance on ad revenue and attract paying subscribers.

Twitter’s general manager for core tech, Nick Caldwell, described Quill as a “fresher, more deliberate way to communicate. We’re bringing their experience and creativity to Twitter as we work to make messaging tools like DMs a more useful and expressive way people can have conversations on the service”.

Users of Quill have until 11 December to export their team message history before the servers are fully shut down at 1pm PST (9pm Irish time). The announcement has instructions for users who wish to import their chat history into Slack and states that all active teams will be issued full refunds.

The team thanked its users and said: “We can’t wait to show you what we’ll be working on next.”

Quill was launched in February with the goal to remove the overwhelming aspects of other messaging services and give users a more deliberate and focused form of online chat.

In an online post, Quill creator Ludwig Pettersson said: “We started Quill to increase the quality of human communication. Excited to keep doing just that, at Twitter.”

The company became a potential competitor for Slack, which was bought by Salesforce at the end of 2020 for $27.7bn. The goal of that acquisition was to combine Salesforce’s CRM platform with Slack’s communications tools to create a unified service tailored to digital-led teams around the world.

Last week, Salesforce announced the promotion of Bret Taylor to vice-chair and co-CEO, just days after he was appointed independent chair of Twitter after CEO Jack Dorsey stepped down.

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