The JUNIPER consortium (‘Joint UNIversities Pandemic and Epidemiological Research’) brings together leading mathematical and statistical modellers from seven UK universities and has received £3 million in funding from UK Research and Innovation (UKRI).

JUNIPER is developing and using customised models to provide predictions and estimates on key questions about the COVID-19 pandemic. These results feed regularly into SPI-M, the modelling group that provides evidence to the Scientific Advisory Group for Emergencies (SAGE) and the wider UK government.

Examples of modelling JUNIPER provides to government includes:

• Understanding how new variants are spreading across the UK and developing statistical models to determine whether new variants are causing more hospitalisations or deaths.
• Forecasting and providing real-time estimates of the R-value, using data from sources such as Pillar 1 and 2 testing, hospital data and mobility data. They are currently providing eight of 12 models contributing real-time R estimates that go from SPI-M to SAGE each week.
• Modelling the effectiveness of different testing strategies on virus transmission and suppression, and modelling the effect of vaccinations and predicting outcomes from different scenarios of how to ease lockdown restrictions.

Professor Julia Gog, co-lead of the consortium from Cambridge’s Department of Applied Mathematics and Theoretical Physics, said: “By bringing research groups together from our seven universities we can provide predictions and estimates about the pandemic to address questions from the government with unprecedented speed. By combining the right expertise together swiftly across research teams we can now respond to questions in less than 24 hours, which might have taken a week for one team working alone. And further, being able to call upon specialist expertise combinations across multiple research groups means we can provide more robust outputs.

“In this unprecedented pandemic, modelling has been hugely important to provide evidence-based predictions and estimates at great speed. Our insights from transmission modelling are fully integrated with scientific evidence from other disciplines and feed into government decision-making.”

Professor Matt Keeling, co-lead of the consortium from the University of Warwick, said: “We’re generating about half the models for the nowcasting that goes into SPI-M and SAGE every week. This consortium allows us to not only boost our speed and capacity, but also to continue to advance the accuracy of our models using the new data and growing knowledge from the pandemic.

“Standard epidemiological modelling tools have worked well so far, but the future with COVID-19 now demands a suite of new tools to deal with the upcoming complexities of the pandemic, such as localised regional outbreaks, growing understanding of socioeconomic differences with this disease, complexities of imperfect vaccines and the growing problem ahead with new variants. Having several teams using different models working on the same problem helps us to verify our results and makes the consortium much bigger than the sum of its parts.”

The consortium is funded as part of UKRI’s COVID-19 Agile Call, which has so far invested more than £150M in over 400 projects to address the impacts of the COVID-19 pandemic.

Professor Charlotte Deane, COVID-19 Response Director at UKRI, said: “This consortium enables disease modellers to pool their expertise nationally to increase the scale, speed and quality of their models of policy options and predictions for the pandemic. They’ll provide cutting-edge evidence about the pandemic into the UK government’s decision-making.”

The consortium will also proactively generate new model-based predictions and develop the necessary methodology as part of a horizon-scanning process.

The consortium plan to make their models open-source, so scientists worldwide can access them and benefit.

The seven universities involved in JUNIPER are Cambridge, Warwick, Exeter, Oxford, Bristol, Manchester and Lancaster Universities.

They will work closely with other organisations and research teams active on COVID-19 research including the Alan Turing Institute, the Royal Statistical Society, Health Data Research UK, Public Health England, the Royal Society’s ‘RAMP’ initiative, and the Isaac Newton Institute for Mathematical Sciences.

The research paves the way for cell therapies to treat liver disease – in other words, growing ‘mini-bile ducts’ in the lab as replacement parts that can be used to restore a patient’s own liver to health – or to repair damaged organ donor livers, so that they can still be used for transplantation.

Bile ducts act as the liver’s waste disposal system, and malfunctioning bile ducts are behind a third of adult and 70 per cent of children’s liver transplantations, with no alternative treatments. There is currently a shortage of liver donors: according to the NHS, the average waiting time for a liver transplant in the UK is 135 days for adults and 73 days for children. This means that only a limited number of patients can benefit from this therapy.

Approaches to increase organ availability or provide an alternative to whole organ transplantation are urgently needed. Cell-based therapies could provide an advantageous alternative. However, the development of these new therapies is often impaired and delayed by the lack of an appropriate model to test their safety and efficacy in humans before embarking in clinical trials.

Now, in a study published today in Science, scientists at the University of Cambridge have developed a new approach that takes advantage of a recent ‘perfusion system’ that can be used to maintain donated organs outside the body. Using this technology, they demonstrated for the first time that it is possible to transplant biliary cells grown in the lab known as cholangiocytes into damaged human livers to repair them. As proof-of-principle for their method, they repaired livers deemed unsuitable for transplantation due to bile duct damage.  This approach could be applied to a diversity of organs and diseases to accelerate the clinical application of cell-based therapy.

“Given the chronic shortage of donor organs, it’s important to look at ways of repairing damaged organs, or even provide alternatives to organ transplantation,” said Dr Fotios Sampaziotis from the Wellcome-MRC Cambridge Stem Cell Institute. “We’ve been using organoids for several years now to understand biology and disease or their regeneration capacity in small animals, but we have always hoped to be able to use them to repair human damaged tissue. Ours is the first study to show, in principle, that this should be possible.”

Bile duct diseases affect only certain ducts while sparing others. This is important because in disease, the ducts in need of repair are often fully destroyed and cholangiocytes may be harvested successfully only from spared ducts.

Using the techniques of single-cell RNA sequencing and organoid culture, the researchers discovered that, although duct cells differ, biliary cells from the gallbladder, which is usually spared by the disease, could be converted to the cells of the bile ducts usually destroyed in disease (intrahepatic ducts) and vice versa using a component of bile known as bile acid.  This means that the patient’s own cells from disease-spared areas could be used to repair destroyed ducts.

To test this hypothesis, the researchers grew gallbladder cells as organoids in the lab. Organoids are clusters of cells that can grow and proliferate in culture, taking on a 3D structure that has the same tissue architecture, function and gene expression and genetic functions as the part of the organ being studied. They then grafted these gallbladder organoids into mice and found that they were indeed able to repair damaged ducts, opening up avenues for regenerative medicine applications in the context of diseases affecting the biliary system.

The team used the technique on human donor livers taking advantage of the perfusion system used by researchers based at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation. They injected the gallbladder organoids into the human liver and showed for the first time that the transplanted organoids repaired the organ’s ducts and restored their function. This study therefore confirmed that their cell-based therapy could be used to repair damaged livers.

Professor Ludovic Vallier from the Wellcome-MRC Cambridge Stem Cell Institute, joint senior author, said: “This is the first time that we’ve been able to show that a human liver can be enhanced or repaired using cells grown in the lab. We have further work to do to test the safety and viability of this approach, but hope we will be able to transfer this into the clinic in the coming years.”

Although the researchers anticipate this approach being used to repair a patient’s own liver, they believe it may also offer a potential way of repairing damaged donor livers, making them suitable for transplant.

Mr Kourosh Saeb-Parsy from the Department of Surgery at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, joint senior author, added: “This is an important step towards allowing us to use organs previously deemed unsuitable for transplantation. In future, it could help reduce the pressure on the transplant waiting list.”

The research was supported by the European Research Council, the National Institute for Health Research and the Academy of Medical Sciences.

Reference
Sampaziotis, F et al. Cholangiocyte organoids can repair bile ducts after transplantation in human liver. Science; 18 Feb 2021

Q: When did you first get the idea to set up Cog-UK? And how was it formed?

In late February 2020, it dawned on me that we were going to need genome sequencing capabilities across the UK for the novel coronavirus. It was predictable that the virus was going to develop mutations that could become problematic.

On March 4, I emailed five colleagues, asking if they’d be interested in helping me set up a UK sequencing consortium. A week later we met at the Wellcome building on Euston Road in London with the aim of thrashing out a plan. We looked to draw in people who might be able to help us put together a blueprint and a network for sequencing in the UK.

There were about 20 people in the meeting. They were clinical virologists, experts in human genomes and pathogen genomes, epidemiologists and immunologists. During that day, we worked through what we thought an end-to-end sequencing pipeline would be, and we debated whether the sequencing would be centralised or distributed or both, and who would do what. By the end of the day, we had the blueprint.

The notes from the meeting were written up into a formal proposal for Sir Patrick Vallance, the UK government’s chief scientific adviser.

It’s unusual because if you have four public health agencies and lots of researchers from different institutions and the NHS, it would take a year or more to do something like that normally. But we just sat down and did it, and that’s how Cog-UK was born.

Q: How did you get funding?

The application was on Sir Patrick Vallance’s desk by March 15. He and Professor Chris Whitty, the chief medical officer for England, had what they called a “COVID-19 fighting fund”. They reviewed our proposal and strongly supported it.

I also contacted Sir Mike Stratton, director of the Wellcome Sanger Institute in Cambridge. I asked Mike if they could support us as they have the technology to do large-scale sequencing. He said yes, and since then, Sanger has contributed a great deal.

So at the outset, we got about £14.5 million from the government, plus in-kind funding from Sanger, which together came to a total of around £20 million.

We started on April 1, but we’d already done quite a lot of sequencing by then. About 260 coronavirus sequences were already in the bag.

Q: So the sequencing began even before Cog-UK was launched?

Because a lot of people had sequencing instruments and expertise, they had already started work. There are sequencing instruments in labs across the country. We hadn’t catalogued where or what at that stage. And, in fact, we weren’t particularly prescriptive about what types of sequencing instruments we asked the labs to use. People used what they thought worked well for them.

Q: How did other scientists react?

They were hugely supportive. Some people were worried that the virus would not accumulate enough mutations to make it worth our while. It would mean that we would end up sequencing the same virus over and over again because it only mutates once or twice a month. It could all have been a waste of time.

What we hadn’t bargained for was the 100 million cases – but perhaps even as high as a billion, if you include undiagnosed cases. And each time the virus infects a person it has an opportunity to make a mistake in its genome.

We considered the risk of lack of genetic variation, but went ahead. What we did was rather bold at the time.

Q: How does it work in practice, from the time someone is swabbed to the time the sequence is uploaded onto the shared Gisaid database that holds all of the world’s sequences of SARS-CoV-2?

Laboratory testing for COVID-19 using the so-called PCR test in the UK is roughly divided into two testing pathways. If you are hospitalised with COVID-19, your sample will get tested in a local laboratory. We call that pillar one.

Cog-UK collects samples from about 90 different laboratories at the moment, which is quite a logistical challenge. These are sent to regional sequencing hubs that focus mostly on sequencing from their region. These are really important samples because they are from the sickest people with COVID-19.

Pillar two testing is done in the Lighthouse labs, which were set up to analyse community testing samples. These are sequenced at the Wellcome Sanger Institute.

We also provide sequencing to major government projects, like the Office for National Statistics study. We also support the React study, [a major programme of home testing for COVID-19 to track the progress of the infection across England] and vaccine trials.

We can’t sequence all of the positive samples at the moment. When we first started, we were aiming for a minimum of 10%. At the moment it’s under 10%, but we hope to get to around 20%, and we’ll build from there.

Q: And as a total of the viruses sequenced in the world, what proportion is Cog-UK sequencing, and how does it compare with other countries?

We have sequenced about 45% to 48% of all SARS-CoV-2 genomes in the Gisaid database.

Q: Given the importance of tracking mutations, are other countries starting to increase their sequencing efforts?

Yes. The country where I think we will see a big shift is the US because of all the changes they’re making in their response to the pandemic. I would anticipate quite a few other countries beginning to come up, too. I know that Germany is looking to increase its sequencing capacity. But there are some really big gaps in the map.

Q: Worrying coronavirus variants have been widely reported on in the last few months. The so-called “UK variant”, B117, was raised as a concern in November, but the sample was from September. Is that right?

Yes, September 20. There were very few cases of B117 initially, and it’s one of hundreds of different variants. So there was no reason to be concerned about it initially. We are learning all the time about which mutations might be important, particularly when they crop up all around the world. So the first time the UK variant was in the database, you probably wouldn’t give it a second thought. It’s only once you start to learn about what the mutations really mean, or when an event occurs, that you start to zoom in on specific variants. And with B117, Public Health England noticed that there was a surge in cases in Kent, which was odd because there was a lockdown and there weren’t any surges elsewhere. That was a striking observation.

So that could be due to human behaviour, such as a super-spreader event. It was at that point, towards the beginning of December, that it became clear that there was not only a surge in cases, but those cases were caused by B117. It had a really striking genome in that it had 23 mutations, which were far more than we were used to seeing. That’s when researchers began to find evidence that it was more transmissible. And it took a bit longer to do the essential science so that we could be certain that this variant was indeed associated with increased transmission.

Q: Why are we suddenly seeing all of these mutations that give the coronavirus an advantage now?

It’s not the first time that we have observed mutations that have given the virus an advantage. At the end of March 2020, we noticed something for the first time in the UK: a mutation in the spike protein called D614G. This wasn’t in the original virus that was first detected in China. But the virus with this mutation rapidly expanded and replaced the other viral lineages circulating at the time.

We talked about this at Sage, the government’s scientific advisory group for emergencies, quite early on. And we calculated that it caused an increase in the R0, which represents the average number of people infected by one infectious individual. So we knew then that this type of event could happen – it was a practice run for more serious variants to come.

The D614G mutation gave the virus a modest increase in transmissibility. But it swept across the world. It’s now present in almost all SARS-CoV-2 viruses.

The next variant to worry people emerged in Denmark and was related to SARS-CoV-2 being transmitted between mink and people – referred to as the “cluster 5 variant”. People were concerned that evolution had been accelerated by passage through mink and had been transmitted back to humans. But only 12 people in Denmark were ever found to have that variant. So that fizzled.

A third worrying variant emerged in Spain in the summer. It seemed to be spreading very quickly around Europe. One possible reason for this was a particular mutation in the spike protein. But over time it became clear that it was being transmitted because people were moving around on their summer holidays. There was no evidence that it was more transmissible.

We also reported to Sage another mutation in the spike protein last October, called N439K. And that change in the spike protein appears to affect the body’s immune response, at least based on laboratory experiments.

So the idea that variants have only just arisen is not the case. We’ve been talking about variants since the early days of the pandemic, which might surprise some people.

Q: Is the original virus from Wuhan still around?

Lineages can expand and then go extinct, so we don’t expect the same lineage to necessarily be around forever. This was shown by work in Wales and in Scotland, where they looked at the lineages in the first wave and then in the second wave.

In the first wave, these were largely imported from Europe. In the summer as cases fell, most of those original lineages disappeared. Then, in the second wave, numerous new lineages were introduced from overseas, which kicked off the second wave. So it’s quite a dynamic process. As particular lineages have a fitness advantage, then that is probably what is circulating at any particular time.

Q: Is there a base type that you compare changes against? And is it the original virus or the current dominant variant?

We compare changes against the original virus sequenced in Wuhan in January 2020 – it’s the reference genome. But it’s quite confusing because different groups use different names and different naming conventions. I hope that the World Health Organization will help us to reach a common international nomenclature.

It worries me that people name variants after where they were first identified. Evolution is not a function of geography, it’s a function of nature. I very much hope that we move away from calling coronaviruses, the UK variant or the South African variant or the Brazilian variant. I tend to try and say the variant first detected in South Africa, or whatever. Because it could be quite stigmatising in the longer term.

Q: Is a certain amount of evolutionary selective pressure created when we start to vaccinate lots of people? Or is the greater number of people in which the virus has the opportunity to mutate the greater problem of the two?

At the moment, I think it’s the number of cases that is important because the variant detected in the UK emerged when vaccines weren’t yet being rolled out, but when cases were high. And the same is true in South Africa and Brazil.

Some people have contacted me to say: “Do you think it was the vaccine trials that led variants to emerge?” But if you compare the relatively small number of people who’ve been in vaccine trials versus the very large number of people who are infected – 100 million people infected. I think the biggest driver of mutation emerging is the number of opportunities the virus has had to mutate.

And people say, “Well, isn’t the vaccine going to drive the emergence of new variants?” It may be one of the pressures, but if you’re in a population where, say, 50% have been infected and have so-called “natural immunity”, then it doesn’t matter how you get the immunity to the virus, the virus will try to find a chink in that armour. But in that instance, it’s a naturally acquired infection rather than immunisation. So this problem has been around long before vaccination.

Q: And of the variants of concern that we know of, which one is the most worrying?

Right now, it’s the variant first detected in South Africa. It has already been reported in 31 countries and identified in 750 sequences so far. Although this is probably a gross underestimate because quite a few countries that surround South Africa do not have sequencing capacity at the moment. This variant appears to be more transmissible in South Africa and reduces the effectiveness of our immune response, be that from natural infection or vaccination.

P1 is also on the watch list. This variant first identified in Brazil has mutations associated with being more transmissible and with a reduced immune response. If you look at the global spread of P1 though, unlike some of the other variants, I don’t really see it taking hold at the moment. It’s been linked to just nine countries so far.

I’m also looking at what else might be emerging in the coming weeks and months. What I’m particularly concerned about is that now that B117 causes almost all COVID-19 cases in the UK – what new mutations will arise in this? This new variant is likely to start to develop constellations of different mutations in its descendants. And what I’m watching for is something like E484K, the “escape mutation”, being increasingly found in B117. So far, this has arisen independently several times and includes a cluster of cases in Bristol and south-west England, but the number of cases is low.

Q: How important is what Cog-UK does to the vaccine effort?

Sequencing is absolutely integral to vaccine development. We are going to need to have sequence data.

We’re going to need to keep sequencing for the foreseeable future so that we can adapt our vaccines to keep them effective. It’s going to be a long-term job to run the two in parallel. Vaccine manufacturers are already working to tweak their vaccines for the South Africa variant, for example, to make sure it’s going to be effective against that variant.

There are going to be new variants arising in the future and we’re going to have to adapt our response to these as we go along. Sequencing and vaccine development are key partners. I suspect that this is going to be ongoing throughout my life and beyond. Of concern is that we don’t have global coverage, so we are not sighted globally in terms of new variants.

Q: So it’s going to be like the flu vaccine every year, depending on how long immunity lasts?

Yes, quite similar, but it might be a bit less predictable than a single vaccine booster each year. SARS-CoV-2 could ratchet up its characteristics over time, and the diversity of mutation combinations in different variants could change over time. So it could be more complex than flu.

We’ve also known that immunity wanes over time. So we’re going to have to be thinking about long-term strategies with this virus.

Sharon Peacock, Director, COVID-19 genomics UK Consortium (COG-UK) and Professor of Public Health & Microbiology, University of Cambridge

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Around 80% of the UK population is currently infected with human cytomegalovirus (HCMV) and in developing countries this can be as high as 95%. The virus can remain dormant in our white blood cells for decades and, if it reactivates in a healthy individual, does not usually cause symptoms. But, for people who are immunocompromised, HCMV reactivation can be devastating. 

HCMV reactivation has been identified in COVID-19 patients, though scientists do not yet understand the relationship between the two viruses. Reactivation or re-infection in transplant recipients can lead to severe illness, including organ rejection and, in some cases, death.

More than 200,000 kidney, lung and stem cell transplants take place globally every year and HCMV reactivation occurs in more than half of these cases. For reasons scientists don’t yet fully understand, immunosuppressants appear to encourage the virus to reactivate as well as compromising the patient’s ability to fight it. There remains no effective vaccine against HCMV and anti-viral therapies often prove ineffective or detrimental.

Now, a team from the University of Cambridge’s School of Clinical Medicine has identified a drug type and treatment strategy that could dramatically reduce these devastating reactivation events. The study, published in the journal PNAS, describes how scientists exposed HCMV-infected blood samples to a wide-range of ‘epigenetic inhibitors’ – drugs widely used in cancer treatment – hoping to prompt the latent virus to produce proteins or targetable antigen that are visible to our immune system. 

They discovered that a particular group of these drugs, ‘bromodomain inhibitors’, successfully reactivated the virus by forcing it to convert its hidden genetic instructions into protein. This then enabled T-cells in the blood samples to target and kill these previously undetectable infected cells. 

The study is the first to identify the involvement of human host bromodomain (BRD) proteins in the regulation of HCMV latency and reactivation but also proposes a novel ‘shock and kill’ treatment strategy to protect transplant patients.

Lead author Dr Ian Groves said: “We’re looking to purge the patient’s viral reservoir before they go into the operating theatre and before they start taking immunosuppressants, when they would become extremely vulnerable to the virus reactivating. In other words, we’re proposing a pre-emptive strike. 

“Prior to transplantation, many patients will have a relatively healthy immune system, so when the virus puts its head above the parapet, its cover is blown, and the immune system will see it and kill the cells it’s been hiding in. Ideally, donors would also be treated to avoid re-infecting recipients.”

There are similar drugs in Phase 1–3 clinical trials around the world for other intended uses, mainly in the treatment of cancers but also Type 2 diabetes-related cardiovascular disease.

Dr Groves said: “This would be the first type of treatment to reduce HCMV infection levels pre-transplant in order to lower the chances of virus reactivation during immune suppression after transplantation. Our findings could lead to thousands of lives being saved every year.”

“In addition to the terrible human suffering this virus causes, treating its effects adds enormously to the high costs already incurred by transplantation. It’s a really serious issue for health services in wealthy nations and a desperate one in developing countries. Our findings offer an opportunity to transform this horrible situation.”

The study builds on over 25 years of extensive research into the molecular biology of HCMV and its immune evasion tactics (funded by the Medical Research Council). The researchers hope their study could eventually help doctors fight HCMV on other fronts, including in maternity and neo-natal care. HCMV affects at least 1% of all live births in developed countries, and many more in developing countries. These children can be left with brain damage and hearing loss, but congenital infection during pregnancy can also lead to miscarriage.

Reference

I. J. Groves et al., ‘Bromodomain proteins regulate human cytomegalovirus latency and reactivation allowing epigenetic therapeutic intervention’. PNAS (2021). DOI: 10.1073/pnas.2023025118

The researchers, from the University of Cambridge, used modelling and high-speed video techniques to show what causes wheezing and how to predict it. Their results could be used as the basis of a cheaper and faster diagnostic for lung disease that requires just a stethoscope and a microphone.

Improved understanding of the physical mechanism responsible for generating wheezing sounds could provide a better causal link between symptoms and disease, and help improve diagnosis and treatment. The results are reported in the journal Royal Society Open Science.

At some point, most of us have experienced wheezing, a high-pitched whistling sound made while breathing. For most people, the phenomenon is temporary and usually the result a cold or mild allergic reaction. However, regular or chronic wheezing is often a symptom of more serious conditions, such as asthma, emphysema, chronic obstructive pulmonary disease (COPD) or certain cancers.

“Because wheezing makes it harder to breathe, it puts an enormous amount of pressure on the lungs,” said first author Dr Alastair Gregory from Cambridge’s Department of Engineering. “The sounds associated with wheezing have been used to make diagnoses for centuries, but the physical mechanisms responsible for the onset of wheezing are poorly understood, and there is no model for predicting when wheezing will occur.”

Co-author Dr Anurag Agarwal, Head of the Acoustics lab in the Department of Engineering, said he first got the idea to study wheezing after a family vacation several years ago. “I started wheezing the first night we were there, which had never happened to me before,” he said. “And as an engineer who studies acoustics, my first thought was how cool it was that my body was making these noises. After a few days however, I was having real trouble breathing, which made the novelty wear off pretty quickly.”

Agarwal’s wheezing was likely caused by a dust mite allergy, which was easily treated with over-the-counter antihistamines. However, after speaking with a neighbour who is also a specialist in respiratory medicine, he learned that even though it is a common occurrence, the physical mechanisms that cause wheezing are somewhat mysterious.

“Since wheezing is associated with so many conditions, it is difficult to be sure of what is wrong with a patient just based on the wheeze, so we’re working on understanding how wheezing sounds are produced so that diagnoses can be more specific,” said Agarwal.

The airways of the lung are a branching network of flexible tubes, called bronchioles, that gradually get shorter and narrower as they get deeper into the lung.

In order to mimic this setup in the lab, the researchers modified a piece of equipment called a Starling resistor, in which airflow is driven through thin elastic tubes of various lengths and thicknesses.

Co-author and computer vision specialist Professor Joan Lasenby developed a multi-camera stereoscopy technique to film the air being forced through the tubes at different degrees of tension, in order to observe the physical mechanisms that cause wheezing.

“It surprised us just how violent the mechanism of wheezing is,” said Gregory, who is also a Junior Research Fellow at Magdalene College. “We found that there are two conditions for wheezing to occur: the first is that the pressure on the tubes is such that one or more of the bronchioles nearly collapses, and the second is that air is forced though the collapsed airway with enough force to drive oscillations.”

Once these conditions are met, the oscillations grow and are sustained by a flutter mechanism in which waves travelling from front to back have the same frequency as the opening and closing of the tube. “A similar phenomenon has been seen in aircraft wings when they fail, or in bridges when they collapse,” said Agarwal. “When up and down vibrations are at the same frequency as clockwise and anticlockwise twisting vibrations, we get flutter that causes the structure to collapse. The same process is at work inside the respiratory system.”

Using these observations, the researchers developed a ‘tube law’ in order to predict when this potentially damaging oscillation might occur, depending on the tube’s material properties, geometry and the amount of tension.

“We then use this law to build a model that can predict the onset of wheezing and could even be the basis of a cheaper and faster diagnostic for lung disease,” said Gregory. “Instead of expensive and time-consuming methods such as x-rays or MRI, we wouldn’t need anything more than a microphone and a stethoscope.”

A diagnostic based on this method would work by using a microphone – early tests were done using the in-built microphone on a normal smartphone – to record the frequency of the wheezing sound and use this to identify which bronchiole is near collapse, and whether the airways are unusually stiff or flexible in order to target treatment. The researchers hope that by finding changes in material properties from wheezing, and locations that wheezes come from, the additional information will make it easier to distinguish between different conditions, although further work in this area is still needed.

Reference:.
A. L. Gregory, A. Agarwal and J. Lasenby. ‘An Experimental Investigation to Model Wheezing in Lungs.’ Royal Society Open Science (2021). DOI: 10.1098/rsos.201951

Last year, Dr Lee and co-winner Tristan Ahtone – then Indigenous Affairs editor for High Country News, now editor-in-chief of the Texas Observer – published a hard-hitting report revealing how 52 American universities built their fortunes using 11 million acres of Native American land, signed over amid violence, corruption and coercion.

Through exhaustive research over several years, the Land-Grab Universities project located 80,000 parcels of land scattered across 24 states, identified their Indigenous owners, and traced every dollar endowed with profits from dispossession in the late nineteenth and early twentieth centuries.

The investigation reconstructed a land area about the size of Denmark that was taken through over 160 land cessions. The dispossessed included the Dakota, Navajo, Apache, Cheyenne, Arapaho and Ojibwe among nearly 250 other tribes, bands and communities. Read more about Dr Lee’s research here. 

On 6 April 2020, High Country News launched an interactive website enabling the public to explore the fully mapped data for themselves and published an open-source data set Lee assembled for future researchers and journalists to build upon.

Since then, a number of the universities at the heart of the story have responded by launching initiatives, changing their land acknowledgment practices and using the report, website, and data set in their teaching. 

Cornell’s American Indian and Indigenous Studies Program (AIISP) has formed a committee to “present information and opinion about the implications of Indigenous dispossession for the university and its responsibility to address that history”. The committee aims to “determine the Indigenous communities affected by Cornell’s land-grab and consult with them about possible remedies.” 

A team at Ohio State University, in partnership with the First Nations Development Institute, has announced that it is working to “open a path toward both a reckoning of this inglorious history within our university community, as well as the conversations necessary with the affected tribes to determine an appropriate path forward." In doing so, they intend to “develop an initial understanding of what specific reparative actions would most benefit the Native American communities impacted by this land dispossession, particularly with respect to food security and sovereignty, and the process by which it could be jointly designed.”

Washington State University has changed its land acknowledgment to incorporate the data.

Dr Lee hopes that land-grant universities will start redirecting income still being derived from the sale of Indigenous land to support Native American students, and that unsold land will eventually be returned.

Dr Lee said: "I was grateful to hear we had received the Polk Award. Since its publication, ‘Land-Grab Universities’ has sparked public conversations about the debts universities owe to Indigenous nations. This recognition will extend its reach. 

“The Polk also has a track record of amplifying innovative forms of journalism. In this case, we combined historical research and investigative reporting in a way one rarely sees practiced. The project was risky in that regard. Hopefully, this award will encourage more collaborations between historians and journalists."

Tristan Ahtone said: "I'm absolutely delighted that 'Land-Grab Universities' has been honored with this award, and hopefully will inspire even more reporters and researchers to dig into the data. It's absolutely critical that more newsrooms dedicate resources to investigative reporting in Indigenous communities, and I hope this project helps to reveal the breadth, and impact, possible when supporting teams focused on Indigenous affairs reporting."

The George Polk awards are conferred annually to honour special achievement in journalism. Winners are chosen from newspapers, magazines, television, radio and online news organizations. Judges place a premium on investigative work that is original, requires digging and resourcefulness, and brings results.

The awards were established in 1949 in memory of CBS correspondent George Polk, who was killed while covering the Greek Civil War. They are conferred annually by New York's Long Island University. Dr Lee and his colleagues at High Country News won the award for Education Reporting.

Read more on the impact of the Land-Grab Universities here.

The use of asymptomatic COVID-19 testing is accelerating in a range of UK settings, including in higher education institutions. The University of Cambridge introduced a weekly asymptomatic testing programme for students in College accommodation in October 2020 as part of its efforts to reduce the spread of COVID-19. The programme, based on laboratory PCR tests facilitated by the national lighthouse laboratory network, involves pooling swabs from students in their households. If the pool tests positive, individual tests are performed for each participating student to investigate further.

Researchers at THIS Institute consulted students and staff at the University on ethical issues relating to its student testing programme. Their views, combined with expert legal and ethical analysis, resulted in a new ethical framework aimed at helping higher education institutions make complex decisions about student testing programmes.

The framework offers recommendations in nine areas:

1. Design and operation of the programme
2. Goals of the programme
3. Properties of the test
4. Enabling isolation
5. Choices regarding participation
6. Benefits, harms and opportunity costs
7. Responsibilities
8. Privacy, confidentiality and data protection
9. Communication

Professor Mary Dixon-Woods, Director of THIS Institute, said: “Higher education institutions must be certain that they can deliver asymptomatic COVID-19 testing programmes for students that are responsive to new evidence, policy and guidance, pandemic conditions, and views of their students and staff. This new ethical framework is intended to help leaders to think through whether asymptomatic COVID-19 testing is the right option for their institution, and to support good organisational decision-making around implementing testing programmes.”

Dr Caitriona Cox, NIHR Academic Clinical Fellow at THIS Institute and project lead, said: “The framework and checklist are freely available and will hopefully act as valuable and timely resources for higher education institutions seeking ethically sound ways to keep people safe and support public health efforts.”

Supported by the Wellcome Trust, Dr Cox and colleagues consulted over 200 students and staff from the University of Cambridge. Participants took part via an online questionnaire or interview. The consultation, conducted through Thiscovery, THIS Institute’s online research platform, gathered views about the asymptomatic COVID-19 testing programme. The consultation findings were integrated with ethical and legal analysis and expert discussion to produce an ethical framework and checklist.

The framework, checklist and further information about the work is available on the THIS Institute website.

By using decades’ worth of data from human motion perception studies, researchers have trained an artificial neural network to estimate the speed and direction of image sequences.

The new system, called MotionNet, is designed to closely match the motion-processing structures inside a human brain. This has allowed the researchers to explore features of human visual processing that cannot be directly measured in the brain.

Their study, published today in the Journal of Vision, uses the artificial system to describe how space and time information is combined in our brain to produce our perceptions, or misperceptions, of moving images.

The brain can be easily fooled. For instance, if there’s a black spot on the left of a screen, which fades while a black spot appears on the right, we will ‘see’ the spot moving from left to right – this is called ‘phi’ motion. But if the spot that appears on the right is white on a dark background, we ‘see’ the spot moving from right to left, in what is known as ‘reverse-phi’ motion.”

The researchers reproduced reverse-phi motion in the MotionNet system, and found that it made the same mistakes in perception as a human brain – but unlike with a human brain, they could look closely at the artificial system to see why this was happening. They found that neurons are ‘tuned’ to the direction of movement, and in MotionNet, ‘reverse-phi’ was triggering neurons tuned to the direction opposite to the actual movement.

The artificial system also revealed new information about this common illusion: the speed of reverse-phi motion is affected by how far apart the dots are, in the reverse to what would be expected. Dots ‘moving’ at a constant speed appear to move faster if spaced a short distance apart, and more slowly if spaced a longer distance apart.

“We’ve known about reverse-phi motion for a long time, but the new model generated a completely new prediction about how we experience it, which no-one has ever looked at or tested before,” said Dr Reuben Rideaux, a researcher in the University of Cambridge’s Department of Psychology and first author of the study.

Humans are reasonably good at working out the speed and direction of a moving object just by looking at it. It’s how we can catch a ball, estimate depth, or decide if it’s safe to cross the road. We do this by processing the changing patterns of light into a perception of motion – but many aspects of how this happens are still not understood.

“It’s very hard to directly measure what’s going on inside the human brain when we perceive motion - even our best medical technology can’t show us the entire system at work. With MotionNet we have complete access,” said Rideaux.

Thinking things are moving at a different speed than they really are can sometimes have catastrophic consequences. For example, people tend to underestimate how fast they are driving in foggy conditions, because dimmer scenery appears to be moving past more slowly than it really is. The researchers showed in a previous study that neurons in our brain are biased towards slow speeds, so when visibility is low they tend to guess that objects are moving more slowly than they actually are.

Revealing more about the reverse-phi illusion is just one example of the way that MotionNet is providing new insights into how we perceive motion. With confidence that the artificial system is solving visual problems in a very similar way to human brains, the researchers hope to fill in many gaps in current understanding of how this part of our brain works.

Predictions from MotionNet will need to be validated in biological experiments, but the researchers say that knowing which part of the brain to focus on will save a lot of time.

Rideaux and his study co-author Dr Andrew Welchman are part of Cambridge’s Adaptive Brain Lab, where a team of researchers is examining the brain mechanisms underlying our ability to perceive the structure of the world around us. 

This research was supported by the Leverhulme Trust and the Isaac Newton Trust.

Reference

Rideaux, R. & Welchman, A.E.: ‘Exploring and explaining properties of motion processing in biological brains using a neural network.’ Journal of Vision, Feb 2021. DOI: 10.1167/jov.21.2.11

Savannah ecosystems, and regions with extreme wet or dry seasons were found to be the most sensitive to changes in fire frequency. Trees in regions with moderate climate are more resistant. Repeated fires also cause less damage to tree species with protective traits like thicker bark.

These effects only emerge over the course of several decades: the effect of a single fire is very different from repeated burning over time. The study found that after 50 years, regions with the most extreme annual fires had 72% lower wood area - a surrogate for biomass - with 63% fewer individual trees than in regions that never burned. Such changes to the tree community can reduce the forest’s long-term ability to store carbon, but may buffer the effect of future fires.

“Planting trees in areas where trees grow rapidly is widely promoted as a way to mitigate climate change. But to be sustainable, plans must consider the possibility of changes in fire frequency and intensity over the longer term,” said Dr Adam Pellegrini in the University of Cambridge’s Department of Plant Sciences, first author of the paper.

He added: “Our study shows that although wetter regions are better for tree growth, they’re also more vulnerable to fire. That will influence the areas we should manage to try and mitigate climate change.”

Past studies have found that frequent fires reduce levels of nutrients - including nitrogen - in the soil. The new study demonstrates that this can favour slower-growing tree species that have adaptations to help them survive with less nutrients. But these tree species also slow down nutrient cycling in the soil - they hold onto what they have. This can limit the recovery of the forest as a whole by reducing the nutrients available for plant growth after an intense fire.

Wildfires are playing an increasingly important role in global carbon emissions. Fire burns five percent of the Earth’s surface every year, releasing carbon dioxide into the atmosphere equivalent to 20% of our annual fossil fuel emissions.

In the past, the majority of carbon released by wildfires was recaptured as ecosystems regenerated. But the more frequent fires of recent years, driven by changes in climate and land use, don’t always allow time for this.

“As fire frequency and intensity increases because of climate change, the structure and functioning of forest ecosystems are going to change in so many ways because of changes in tree composition,” said Pellegrini.

He added:  “More fire-tolerant tree species are generally slower growing, reducing the productivity of the forest. As climate change causes wildfires to become more intense and droughts more severe, it could hamper the ability of forests to recover - reducing their capacity for carbon storage.”

The study is the largest of its type ever to be undertaken. Researchers analysed data from a global network of 374 plots distributed across 29 sites throughout four continents, where plots have experienced different fire frequencies and intensities for multiple decades.

The network spans a broad geographical range of ecosystems from African and Australian savannahs and grasslands, to forests in Europe and North America. These are all ecosystems that experience natural burning, or would do if humans weren’t suppressing fires.

This research was funded by the USDA National Institute of Food and Agriculture, and the Gordon and Betty Moore Foundation.

Reference

Pellegrini, A.F.A. et al: ‘Decadal changes in fire frequencies shift tree communities and functional traits.’ Nature Ecology & Evolution, February 2021. DOI: 10.1038/s41559-021-01401-7

Read more about Adam Pellegrini's work in Fire: The Great Manipulator

The study by a team at Cambridge University Hospitals NHS Foundation Trust (CUH) and the University of Cambridge analysed results from thousands of COVID-19 tests carried out each week as part its screening programmes on hospital staff who showed no signs of infection.

Vaccination for health care workers on the CUH site began on 8 December 2020, with mass vaccination from 8 January 2021. During a two-week period between 18 and 31 January 2021, the team screened similar numbers of vaccinated and unvaccinated staff using around 4,400 PCR tests per week. 

The results were then separated out to identify unvaccinated staff, and staff who had been vaccinated more than 12 days prior to testing (when protection against symptomatic infection is thought to occur).
The study, which is yet to be peer-reviewed, found that 26 out of 3,252 (0·80%) tests from unvaccinated healthcare workers were positive. This compared to 13 out of 3,535 (0.37%) tests from healthcare workers less than 12 days post-vaccination and 4 out of 1,989 (0·20%) tests from healthcare workers at 12 days or more post-vaccination.

This suggests a four-fold decrease in the risk of asymptomatic COVID-19 infection amongst healthcare workers who have been vaccinated for more than 12 days (75 per cent protection). The level of asymptomatic infection was also halved in those vaccinated for less than 12 days.

Dr Mike Weekes, an infectious disease specialist at CUH and the University of Cambridge’s Department of Medicine, who led the study, said:  “This is great news – the Pfizer vaccine not only provides protection against becoming ill from SARS-CoV-2 but also helps prevent infection, reducing the potential for the virus to be passed on to others.

“This will be welcome news as we begin to plot a roadmap out of the lockdown, but we have to remember that the vaccine doesn’t give complete protection for everyone. We still need social distancing, masks, hand hygiene and regular testing until the pandemic is under much better control.” 

Dr Nick Jones, first author on the study and an infectious diseases/microbiology registrar at CUH, said: “Our findings show a dramatic reduction in the rate of positive screening tests among asymptomatic healthcare workers after a single dose of the Pfizer-BioNTech vaccine. This is fantastic news for both hospital staff and patients, who can be reassured that the current mass vaccination strategy is protecting against asymptomatic carriage of the virus in addition to symptomatic disease, thereby making hospitals even safer places to be.”

Giles Wright, programme director for the CUH Vaccination Hub said:  “Throughout the pandemic so far, we have taken a systematic approach to keeping our staff safe and well. The huge efforts of all those involved in the testing, tracing and vaccination programmes at CUH are making the plan a reality. We are very encouraged by the findings of our research. It gives further hope for the near future.”

When the team included symptomatic healthcare workers, their analyses showed similar reductions. 56 out of 3,282 (1·71%) unvaccinated healthcare workers tested positive. This compared to 8 out of 1,997 (0·40%) healthcare workers at 12 or more days post-vaccination, a 4·3-fold reduction.

The researchers have released their data ahead of peer review because of the urgent need to share information relating to the pandemic.

This work was supported by Wellcome, the Medical Research Council, NHS Blood & Transplant, Addenbrooke’s Charitable Trust and the NIHR Cambridge Biomedical Research Centre.

Reference
Jones, NK et al. Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection. 24 Feb 2020; DOI: 10.22541/au.161420511.12987747/v1

The results, published today in the journal Proceedings of the Royal Society B, provide the first evidence of a link between self-control and intelligence in a non-primate species.

To conduct the experiment, common cuttlefish (Sepia officinalis) in tanks were presented with two foods they commonly eat, each in a separate Perspex chamber. In one chamber was a piece of king prawn, which they could eat immediately. In the other was a live grass shrimp, their preferred food, but they could only have the shrimp if they waited and didn’t eat the prawn.

A range of delays were tested, starting at 10 seconds and increasing by 10 seconds each time. All six cuttlefish in the experiment showed self-control, waiting for the grass shrimp and ignoring the king prawn. Those with the most self-control could wait 130 seconds for the grass shrimp to be released – an ability comparable with large-brained animals like chimpanzees.

“It was quite astonishing that the cuttlefish could wait for over two minutes for a better snack. Why would a fast-growing animal with an average life-span of less than two years be a picky eater?” said Dr Alexandra Schnell in the University of Cambridge’s Department of Psychology, first author of the paper.

The learning ability of each cuttlefish was then tested in a different task. A dark grey marker and a white marker were placed in random positions in the tank. After learning to associate one colour with a reward, the reward was switched to be associated with the other colour. The cuttlefish that were both quicker to learn the association and quicker to realise the switch were the same ones showing more self-control in the first task.

“We found that cuttlefish with better learning performance - an indicator of intelligence - also showed better self-control. This link exists in humans and chimpanzees, but this is the first time it has been shown in a non-primate species,” said Schnell.

The researchers suggest that self-control in cuttlefish is the by-product of another behaviour: staying camouflaged on the sea bed for long periods of time to avoid predators. These periods are punctuated by brief foraging bouts in the open. Self-control may help the cuttlefish optimise their foraging by only striking prey of better quality.

“The ability to exert self-control is an important element of the ability to plan for the future, which is quite a sophisticated behaviour,” said Professor Nicola Clayton FRS in Cambridge’s Department of Psychology, senior author of the report.

She added: “Self-control requires an understanding that ‘less is sometimes more’ - that avoiding temptation now might lead to a better future outcome. This is a critically important building block for the evolution of complex decision-making.”

The researchers also noticed that the cuttlefish in the self-control task turned their bodies away from the immediately available food, as if to distract themselves from eating it.

Self-control - the ability to resist temptation in favour of a better but delayed reward – is a vital skill that underpins effective decision-making, goal-directed behaviour and future planning. Amongst animals, apes and their clever feathered cousins, the corvids and parrots, have relatively high self-control when it comes to eating. Rats, chickens and pigeons find it much more difficult not to eat food immediately.

The experiments were conducted with collaborators including Professor Roger Hanlon at the Marine Biological Laboratory in Woods Hole, Massachusetts. Their design was inspired by the 1972 Stanford marshmallow test, in which children were offered a choice between one marshmallow immediately, or two if they waited for a period of time.

Two additional cuttlefish were recruited to the study but refused to take part.

This research was funded by the Royal Society.

Reference

Schnell, A.K. et al: ‘Cuttlefish exert self-control in a delay of gratification task.’ Proceedings of the Royal Society B, March 2021. DOI: 10.1098/rspb.2020.3161

Polaritons are quantum particles that consist of a photon and an exciton, another quasiparticle, combining light and matter in a curious union that opens up a multitude of possibilities in next-generation devices.

The researchers have shown that geometrically coupled polariton condensates, which appear in semiconductor devices, are capable of simulating molecules with various properties.

Ordinary molecules are groups of atoms bound together with molecular bonds, and their physical properties differ from those of their constituent atoms quite drastically: consider the water molecule, H₂O, and elemental hydrogen and oxygen.

“In our work, we show that clusters of interacting polaritonic and photonic condensates can form a range of exotic and entirely distinct entities – ‘molecules’ – that can be manipulated artificially,” said first author Alexander Johnston, from Cambridge Department of Applied Mathematics and Theoretical Physics. “These artificial molecules possess new energy states, optical properties, and vibrational modes from those of the condensates comprising them.”

Johnston and his colleagues – Kirill Kalinin from DAMTP and Professor Natalia Berloff, who holds joint positions at Cambridge and Skoltech – were running numerical simulations of two, three, and four interacting polariton condensates, when they noticed some curious asymmetric stationary states in which not all of the condensates have the same density in their ground state.

“Upon further investigation, we found that such states came in a wide variety of different forms, which could be controlled by manipulating certain physical parameters of the system,” said Johnston. “This led us to propose such phenomena as artificial polariton molecules and to investigate their potential uses in quantum information systems.”

In particular, the team focused on an ‘asymmetric dyad’, which consists of two interacting condensates with unequal occupations. When two of those dyads are combined into a tetrad structure, the latter is, in some sense, analogous to a homonuclear molecule – for instance, to molecular hydrogen H₂. Furthermore, artificial polariton molecules can also form more elaborate structures, which could be thought of as artificial polariton compounds.

“There is nothing preventing more complex structures from being created,” said Johnston. “We’ve found that there is a wide range of exotic, asymmetric states possible in tetrad configurations. In some of these, all condensates have different densities, despite all of the couplings being of equal strength, inviting an analogy with chemical compounds.”

In specific tetrad structures, each asymmetric dyad can be viewed as an individual ‘spin,’ defined by the orientation of the density asymmetry. This has interesting consequences for the system’s degrees of freedom, or the independent physical parameters required to define states. The spins introduce a separate degree of freedom, in addition to the continuous degrees of freedom given by the condensate phases.

The relative orientation of each of the dyads can be controlled by varying the coupling strength between them. Since quantum information sem.

“In addition, we have discovered a plethora of exotic asymmetric states in triad and tetrad systems,” said Berloff. “It is possible to seamlessly transition between such states simply by varying the pumping strength used to form the condensates. This property suggests that such states could form the basis of a polaritonic multi-valued logic system, which could enable the development of polaritonic devices that dissipate significantly less power than traditional methods and, potentially, operate orders of magnitude faster.”

Reference:
Alexander Johnston, Kirill P. Kalinin, and Natalia G. Berloff. ‘Artificial polariton molecules.’ Physical Review Letters B (2021). DOI: 10.1103/PhysRevB.103.L060507

Adapted from a Skoltech press release.

Care homes are at high risk of experiencing outbreaks of COVID-19, the disease caused by SARS-CoV-2. Older people and those affected by heart disease, respiratory disease and type 2 diabetes – all of which increase with age – are at greatest risk of severe disease and even death, making the care home population especially vulnerable.

Care homes are known to be high-risk settings for infectious diseases, owing to a combination of the underlying vulnerability of residents who are often frail and elderly, the shared living environment with multiple communal spaces, and the high number of contacts between residents, staff and visitors in an enclosed space.

In research published today in eLife, a team led by scientists at the University of Cambridge and Wellcome Sanger Institute used a combination of genome sequencing and detailed epidemiological information to examine the impact of COVID-19 on care homes and to look at how the virus spreads in these settings.

SARS-CoV-2 is an RNA virus and as such its genetic code is prone to errors each time it replicates. It is currently estimated that the virus mutates at a rate of 2.5 nucleotides (the A, C, G and U of its genetic code) per month. Reading – or ‘sequencing’ – the genetic code of the virus can provide valuable information on its biology and transmission. It allows researchers to create ‘family trees’ – known as phylogenetic trees – that show how samples relate to each other.

Scientists and clinicians in Cambridge have pioneered the use of genome sequencing and epidemiological information to trace outbreaks and transmission networks in hospitals and community-based healthcare settings, helping inform infection control measures and break the chains of transmission. Since March 2020, they have been applying this method to SARS-CoV-2 as part of the COVID-19 Genomics UK (COG-UK) Consortium.

In this new study, researchers analysed samples collected from 6,600 patients between 26 February and 10 May 2020 and tested at the Public Health England (PHE) Laboratory in Cambridge. Out of all the cases, 1,167 (18%) were care home residents from 337 care homes, 193 of which were residential homes and 144 nursing homes, the majority in the East of England. The median age of care home residents was 86 years.

While the median number of cases per care home was two, the ten care homes with the largest number of cases accounted for 164 cases. There was a slight trend for nursing homes to have more cases per home than residential homes, with a median of three cases.

Compared with non-care home residents admitted to hospital with COVID-19, hospitalised care home residents were less likely to be admitted to intensive care units (less than 7% versus 21%) and more likely to die (47% versus 20%).

The researchers also explored links between care homes and hospitals. 68% of care home residents were admitted to hospital during the study period. 57% were admitted with COVID-19, 6% of cases had suspected hospital-acquired infection, and 33% were discharged from hospital within 7 days of a positive test. These findings highlight the ample opportunities for SARS-CoV-2 transmission between hospital and care home settings.

When the researchers examined the viral sequences, they found that for several of the care homes with the highest number of cases, all of the cases clustered closely together on a phylogenetic tree with either identical genomes or just one base pair difference. This was consistent with a single outbreak spreading within the care home.

By contrast, for several other care homes, cases were distributed across the phylogenetic tree, with more widespread genetic differences, suggesting that each of these cases was independent and not related to a shared transmission source.

“Older people, particularly those in care homes who may be frail, are at particular risk from COVID-19, so it’s essential we do all that we can to protect them,” said Dr Estée Török, an Honorary Consultant at Addenbrooke's Hospital, Cambridge University Hospitals (CUH), and an Honorary Senior Visiting Fellow at the University of Cambridge.

“Preventing the introduction of new infections into care homes should be a key priority to limit outbreaks, alongside infection control efforts to limit transmission within care homes, including once an outbreak has been identified.”

The team found two clusters that were linked to healthcare workers. One of these involved care home residents, a carer from that home and another from an unknown care home, paramedics and people living with them. The second involved several care home residents and acute medical staff at Cambridge University Hospitals NHS Foundation Trust who cared for at least one of the residents. It was not possible to say where these clusters originated from and how the virus spread.

“Using this technique of ‘genomic surveillance’ can help institutions such as care homes and hospitals better understand the transmission networks that allow the spread of COVID-19,” added Dr William Hamilton from the University of Cambridge and CUH. “This can then inform infection control measures, helping ensure that these places are as safe as possible for residents, patients, staff and visitors.”

The absolute number of diagnosed COVID-19 cases from care home residents declined more slowly in April than for non-care home residents, increasing the proportion of cases from care homes and contributing to the slow rate of decline in total case numbers during April and early May 2020.

“Our data suggest that care home transmission was more resistant to lockdown measures than non-care home settings. This may reflect the underlying vulnerability of the care home population, and the infection control challenges of nursing multiple residents who may also share communal living spaces,” said Gerry Tonkin-Hill from the Wellcome Sanger Institute.

The team found no new viral lineages from outside the UK, which may reflect the success of travel restrictions in limiting new viral introductions into the general population during the first epidemic wave and lockdown period.

This work was funded by COG-UK, Wellcome, the Academy of Medical Sciences, the Health Foundation and the NIHR Cambridge Biomedical Research Centre.

Reference
Hamilton, W et al. COVID-19 infection dynamics in care homes in the East of England: a retrospective genomic epidemiology study. eLife; 2 March 2021; DIO: 10.7554/eLife.64618

Anyone who has drained a bathtub or stirred cream into coffee has seen a vortex, a ubiquitous formation that appears when fluid circulates. But unlike water, fluids governed by the strange rules of quantum mechanics have a special restriction: as was first predicted in 1945 by future Nobel winner Lars Onsager, a vortex in a quantum fluid can only twist by whole-number units.

These rotating structures are predicted to be widely useful for studying everything from quantum systems to black holes. But while the smallest possible quantum vortex, with a single unit of rotation, has been seen in many systems, larger vortices are not stable. While scientists have attempted to force larger vortices to hold themselves together, the results have been mixed: when the vortices have been formed, the severity of the methods used have generally destroyed their usefulness.

Now, Samuel Alperin and Professor Natalia Berloff from the University of Cambridge have discovered a theoretical mechanism through which giant quantum vortices are not only stable but form by themselves in otherwise near-uniform fluids. The findings, published in the journal Optica, could pave the way for experiments that might provide insight into the nature of rotating black holes that have similarities with giant quantum vortices.

To do this, the researchers used a quantum hybrid of light and matter, called a polariton. These particles are formed by shining laser light onto specially layered materials. “When the light gets trapped in the layers, the light and the matter become inseparable, and it becomes more practical to look at the resulting substance as something that is distinct from either light or matter, while inheriting properties of both,” said Alperin, a PhD student at Cambridge’s Department of Applied Mathematics and Theoretical Physics.

One of the most significant properties of polaritons comes from the simple fact that light can’t be trapped forever. A fluid of polaritons, which requires a high density of the exotic particles, is constantly expelling light, and needs to be fed with fresh light from the laser to survive. “The result,” said Alperin, “is a fluid which is never allowed to settle, and which doesn’t need to obey what are usually basic restrictions in physics, like the conservation of energy. Here the energy can change as a part of the dynamics of the fluid.”

It was exactly these constant flows of liquid light that the researchers exploited to allow the elusive giant vortex to form. Instead of shining the laser on the polariton fluid itself, the new proposal has the light shaped like a ring, causing a constant inward flow similarly to how water flows to a bathtub drain. According to the theory, this flow is enough to concentrate any rotation into a single giant vortex.

“That the giant vortex really can exist under conditions that are amenable to their study and technical use was quite surprising,” Alperin said, “but really it just goes to show how utterly distinct the hydrodynamics of polaritons are from more well-studied quantum fluids. It’s exciting territory.”

The researchers say that they are just at the beginning of their work on giant quantum vortices. They were able to simulate the collision of several quantum vortices as they dance around each other with ever increasing speed until they collide to form a single giant vortex analogous to the collision of black holes. They also explained the instabilities that limit the maximum vortex size while exploring intricate physics of the vortex behaviour.

“These structures have some interesting acoustic properties: they have acoustic resonances that depend on their rotation, so they sort of sing information about themselves,” said Alperin. “Mathematically, it’s quite analogous to the way that rotating black holes radiate information about their own properties.”

The researchers hope that the similarity could lead to new insights into the theory of quantum fluid dynamics, but they also say that polaritons might be a useful tool to study the behaviour of black holes.

Professor Berloff is jointly affiliated with Cambridge and the Skolkovo Institute of Science and Technology in Russia. 

Reference:
Samuel N. Alperin and Natalia G. Berloff. ‘Multiply charged vortex states of polariton condensates.’ Optica (2021). DOI: 10.1364/OPTICA.418377

Events marking International Women’s Day - on March 8 - will take place across the collegiate University and its institutions, raising awareness about women’s equality, the achievements of the past and the focus on the future.

Among them, the University’s International Women’s Day Lecture will see Dr Nicola Rollock, Senior Adviser on Race to the Vice-Chancellor, in conversation with Professor Stephen J Toope, Vice-Chancellor of the University, discussing race, gender and identity.

A talk by Professor Sarah Hawkes, Director of the Centre for Gender and Global Health, University College London, will be hosted by the School of Clinical Medicine and reflect on the challenges of the COVID-19 pandemic and the role of sex and gender in addressing them. And an event organised by Cambridge Assessment will feature author Patricia Seabright exploring gender inequality and the importance of women choosing to challenge in order to create a more equal society. Meanwhile, the Museum of Zoology is presenting a panel of women engaged with conservation projects around the world.

College events are also taking place, including female author roundtables, discussions around STEMM, and a conference on gender research and lived experience. Elsewhere, social media campaigns, blogs and Spotify playlists will recognise inspirational women.

Professor Val Gibson, the University’s Equality Champion focusing on STEMM subjects, said: “International Women’s Day is an opportunity to reflect and celebrate the many contributions of women to the University’s education and research, including to our collaborations across the world. It is particularly poignant at a time when family, friends and colleagues may be separated and our interactions occur via a virtual setting. It is from this space that I send a huge thank you to all who actively contribute to gender equality, and diversity and inclusion, and the women who make Cambridge such a wonderful place to work.

“The annual International Women’s Day events are always inspirational, and even more so this year. I will spend an enjoyable afternoon listening to all that they have to offer and take from them ideas to further advance gender equality in the University.”

Jenny Rampling and Amy Dolben, Co-Chairs of the University's Women’s Staff Network, said: “At the University of Cambridge, we are privileged to have so many extraordinary women among our staff, students and alumni. International Women’s Day is a global day celebrating the social, economic, cultural, and political achievements of women. However, it also marks a call to action for accelerating gender parity within the institution – from reducing the gender pay gap to ensuring equality of opportunity and supporting staff with caring responsibilities. This is particularly pertinent during the ongoing pandemic as women have borne both the financial and emotional brunt of COVID-19.

"The theme for this year’s International Women’s Day is ‘Choose to Challenge’. As Co-Chairs of the University of Cambridge Women’s Staff Network, we choose to challenge and call out gender bias and inequality. We are also partnering with the Women’s Higher Education Network (WHEN) to campaign for women’s equality across the higher education sector.”

The University of Cambridge Women’s Staff Network seeks to empower, support and inspire through events, networking opportunities and sharing experiences via its members. To join the Women’s Staff Network you can subscribe to the mailing list to receive news and information about events. Join the mailing list here.

This year’s International Women’s Day events include:

New Hall Society International Day Celebration, Murray Edwards College
Saturday 6 March, 11am

Postgraduate students will give presentations about the lives of women around the world:
• Sophie Harbour – gender-based violence in South Africa
• Kanika Mahajan – violence against women and effective ways to bring about change in India
• Tania Mejia-O’Donnell – women’s representation and treatment in US prisons
This will be followed by a Bollywood dance lesson led by the founder of the Cambridge University Bollywood Dance Troupe (back by popular demand!)
The event is being hosted on Zoom and is free to Murray Edwards students and alumnae. More information here.
 

School of Clinical Medicine International Women’s Day Event - Thinking about sex and gender: how can this help us address COVID-19?
Monday 8 March, 12.30pm-1.30pm

The University of Cambridge School of Clinical Medicine is marking IWD2021 with a reflection on the challenges of the COVID-19 pandemic. Professor Sarah Hawkes, Director of the Centre for Gender and Global Health, University College London and Co-Founder of Global Health 50/50, is guest speaker.
More information here.
 

Cambridge Assessment - International Women’s Day talk with Patricia Seabright
Monday 8 March, 3.30pm-4.30pm

Cambridge Assessment Women in Leadership staff network is organising a talk by Patricia Seabright, author of She Said! A Guide for Millennial Women to Speaking and Being Heard. There will also be a panel discussion with Patricia Seabright, Jane Mann (Managing Director of CPE), Pamela Baxter (Director of Cambridge Exams Publishing) and Andrew Nye (Head of New Product Development, Cambridge English). More information here.
 

UIS International Women's Day Event
Monday 8 March, 3pm-4.30pm

This is an online event with a diverse range of speakers and talks. Speakers include Dr Stephen Cave (Executive Director of the Leverhulme Centre for the Future of Intelligence), Dr Eleanor Drage and Dr Kerry Mackereth (Post-doctoral Research Associates at the Centre for Gender Studies), Michelle Child (Operations Director/ Engineering Industry Professional) and Prof Dame Sandra Dawson (KPMG Professor Emeritus of Management Studies).
More information here.
 

University of Cambridge 2021 International Women’s Day Lecture
Monday 8 March, 4pm-5.15pm

Dr Nicola Rollock, Senior Adviser on Race to the Vice-Chancellor, and Professor Stephen J Toope, Vice-Chancellor of the University, discuss race, gender and identity at the University of Cambridge as part of International Women’s Day celebrations.
More information here.
 

Inspiring Conservation on International Women's Day, Museum of Zoology
Monday 8 March, 5pm-6pm

The past 12 months have changed the world, but there are reasons for optimism in nature. Join a panel of amazing women and be inspired by the young people and communities engaged with conservation projects around the world, from saving elephants in Zambia to youth power protecting habitats in the Philippines, educating the next generation of ornithologists in India and more.
More information here.
 

International Women’s Day Celebration, hosted by the St Catharine's FemSoc and Shirley Society 
Monday 8 March, 6pm-7pm 

Come and listen or take part in this International Women’s Day celebration! The theme is ‘challenge’. If you have any anecdotes, short stories, art or anything you would like to share at this event (anonymous or otherwise), please submit them to the online form. Perhaps you want to share the women/non-binary people who have inspired you, or have thoughts on how art can challenge sexism in society? The deadline for submissions is Saturday 6 March.
More information here.

Wolfson College’s International Women’s Day Conference
Monday 8 March, 6pm-9pm 

A joint effort between our WCSA Women's Reps and the Interdisciplinary Research Hub on Gender, this virtual conference provides a safe and supportive environment for Wolfson College members to discuss their work and lived experiences. Our speakers are grouped into three panels, each of which is tied together through a common theme. Panellists will be given the opportunity to share their expertise, followed by a moderated discussion to engage with audience questions. 
More information here.

The Female Voice: Celebrating the Women Authors of Magdalene
Monday 8 March, 6.30pm

Join us as we celebrate International Women’s Day with a roundtable discussion featuring some of Magdalene’s female authors.
What is your process of writing? How did you discover your voice as an author? What inspires your characters? What challenges did you face in getting published? Members and friends are invited to attend a webinar and Q&A with four of Magdalene's recently published fiction writers to discuss their experiences of becoming an author.
More information here. 
 

International Women’s Day: Celebrating Hughes Hall Women in STEM
Monday 8 March, 7pm-8.15pm

We are very pleased to be hosting this event on International Women’s Day 2021, as we place a spotlight on the work of a number of inspirational Hughes Hall women. Our panellists are all Hughesians working and studying in STEM subjects, who will be discussing their careers, research and journeys into their chosen field.
Presentations will be followed by a Q&A and panel discussion.
More information here.
 

From Mississippi to Cambridge: Marie Battle Singer, Britain's first Black psychoanalyst, Wolfson College
Wednesday 10 March, 6pm-7pm

Webinar discussing the life achievements of Marie Battle Singer, who navigated race, gender, and national identity on both sides of the Atlantic.
More information here.

Other activities marking International Women’s Day include:

Robinson Women social media campaign

A month-long social media campaign has been launched to recognise some of the Robinson College community’s inspirational women, among them an Army colonel, cancer researcher, award-winning filmmaker, forensic psychiatrist, charity leaders, eco-tourism entrepreneur, public health professor, aerospace engineer, sustainable sourcing expert, motorsport concussion researcher, goat farmer, and more. Follow us on Facebook, LinkedIn, Twitter and Instagram. #IWD #IWD2021 #RobinsonWomen
 

Blog: Clare Hall Honorary Fellow Melanne Verveer discusses gender equality in the US

A blog by Honorary Fellow of Clare Hall Melanne Verveer – who was Chief of Staff to Hillary Clinton as first lady - reflects on her career addressing gender equality in the US and touches on the disproportionately negative impact COVID-19 has had on women.
 

Gateway Women series by Murray Edwards College

The second alumnae interview of Murray Edwards’ ‘Gateway Women’ series will be published to mark International Women’s Day. The series celebrates 10 years of the College’s Gateway Programme, with 10 alumnae invited to share their experiences of Gateway and discuss their careers since leaving the College.
More information here.

IWD21 playlist by Newnham College’s Royal Literary Fund Fellow Zoe Howe

Newnham's RLF Writing Fellow / music author Zoë Howe has curated an eclectic female-led playlist to inspire Newnham students this International Women's Day! The playlist includes artists Zoë has worked with musically or written books about.
More information here.

The researchers, led by scientists at the University of Cambridge, say that the impact of COVID-19 on diphtheria vaccination schedules, coupled with a rise in the number of infections, risk the disease once more becoming a major global threat.

Diphtheria is a highly contagious infection that can affect the nose and throat, and sometimes the skin. If left untreated it can prove fatal. In the UK and other high-income countries, babies are vaccinated against infection. However, in low- and middle-income countries, the disease can still cause sporadic infections or outbreaks in unvaccinated and partially-vaccinated communities.

The number of diphtheria cases reported globally has being increasing gradually. In 2018, there were 16,651 reported cases, more than double the yearly average for 1996–2017 (8,105 cases).

Diphtheria is primarily caused by the bacterium Corynebacterium diphtheriae and is mainly spread by coughs and sneezes, or through close contact with someone who is infected. In most cases, the bacteria cause acute infections, driven by the diphtheria toxin – the key target of the vaccine. However, non-toxigenic C. diphtheria can also cause disease, often in the form of systemic infections.

In a study published today in Nature Communications,  an international team of researchers from the UK and India used genomics to map infections, including a subset from India, where over half of the globally reported cases occurred in 2018.

By analysing the genomes of 61 bacteria isolated from patients and combining these with 441 publicly available genomes, the researchers were able to build a phylogenetic tree – a genetic ‘family tree’ – to see how the infections are related and understand how they spread. They also used this information to assess the presence of antimicrobial resistance (AMR) genes and assess toxin variation.

The researchers found clusters to genetically-similar bacteria isolated from multiple continents, most commonly Asia and Europe. This indicates that C. diphtheriae has been established in the human population for at least over a century, spreading across the globe as populations migrated.

The main disease-causing component of C. diphtheriae is the diphtheria toxin, which is encoded by the tox gene. It is this component that is targeted by vaccines. In total, the researchers found 18 different variants of the tox gene, of which several had the potential to change the structure of the toxin.

Professor Gordon Dougan from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) said: ““The diphtheria vaccine is designed to neutralise the toxin, so any genetic variants that change the toxin’s structure could have an impact on how effective the vaccine is. While our data doesn’t suggest the currently used vaccine will be ineffective, the fact that we are seeing an ever-increasing diversity of tox variants suggests that the vaccine, and treatments that target the toxin, need to be appraised on a regular basis.”

Diphtheria infections can usually be treated with a number of classes of antibiotic. While C. diphtheriae resistant to antibiotics have been reported, the extent of such resistance remains largely unknown.

When the team looked for genes that might confer some degree of resistance to antimicrobials, they found that the average number of AMR genes per genome was increasing each decade. Genomes of bacteria isolated from infections from the most recent decade (2010-19) showed the highest average number of AMR genes per genome, almost four times as many on average than in the next highest decade, the 1990s.

Robert Will, a PhD student at CITIID and the study’s first author, said: “The C. diphtheriae genome is complex and incredibly diverse. It’s acquiring resistance to antibiotics that are not even clinically used in the treatment of diphtheria. There must be other factors at play, such as asymptomatic infection and exposure to a plethora of antibiotics meant for treating other diseases.”

Erythromycin and penicillin are the traditionally recommended antibiotics of choice for treating confirmed cases of early-stage diphtheria, though there are several different classes of antibiotics available to treat the infection. The team identified variants resistant to six of these classes in isolates from the 2010s, higher than in any other decades.

Dr Pankaj Bhatnagar from the World Health Organization country office for India said: “AMR has rarely been considered as a major problem in the treatment of diphtheria, but in some parts of the world, the bacterial genomes are acquiring resistance to numerous classes of antibiotics. There are likely to be a number of reasons to this, including exposure of the bacteria to antibiotics in their environment or in asymptomatic patients being treated against other infections.”

The researchers say that COVID-19 has had a negative impact on childhood vaccination schedules worldwide and comes at a time when reported case numbers are rising, with 2018 showing the highest incidence in 22 years.

Dr Ankur Mutreja from CITIID, who led the study, said: “It’s more important than ever that we understand how diphtheria is evolving and spreading. Genome sequencing gives us a powerful tool for observing this in real time, allowing public health agencies to take action before it’s too late.

“We mustn’t take our eye off the ball with diphtheria, otherwise we risk it becoming a major global threat again, potentially in a modified, better adapted, form.”

The research was funded primarily by the Medical Research Council, with additional support from the NIHR Cambridge Biomedical Research Centre.

Reference
Will, RC et al. Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheria. Nat Comms; 8 Mar 2021; DOI: 10.1038/s41467-021-21870-5 

Ten years ago, Professor Dame Amanda Fisher, Director of the MRC London Institute of Medical Sciences (then Clinical Sciences Centre), and Vivienne Parry OBE, science writer and broadcaster, concocted an idea to celebrate the contributions that women scientists have made to their field, sometimes overlooked in favour of their male counterparts. With an endorsement from Dr Helen Pankhurst CBE, women’s rights activist and great-granddaughter of Emmeline Pankhurst, they called the awards scheme Suffrage Science.

Their awards were hand-crafted items of jewellery created by art students from Central Saint Martins-UAL, who worked with scientists to design pieces inspired by research and by the Suffragette movement. But rather than produce a new set of pieces for the next awards, each holder chose who they would like to pass their award onto, thus generating an extensive ‘family tree’ of incredible scientists and communicators.

As the relay continued, new branches of the Suffrage Science scheme were developed – the Engineering and Physical Sciences strand was founded in 2013, and the ‘Maths and Computing’ strand followed in 2016. The Suffrage Science family is now 148 strong, with a further 12 joining on Monday 8 March 2021, the tenth anniversary of the scheme.

Each previous holder chose to whom they wanted to pass their ‘heirloom’ piece of jewellery.

Professor Serena Best from Cambridge’s Department of Materials Science and Metallurgy, who was honoured in 2020, chose to pass her award to her colleague Professor Ruth Cameron. She said: “Professor Ruth Cameron is a highly successful and respected scientist in the field of biomaterials whose organisational abilities and communication skills are outstanding. Most recently, she has become the first female appointee to lead the Department of Materials Science and Metallurgy, University of Cambridge in the Office of Head of Department. Ruth’s work ethic will provide inspiration to the next generation of young female scientists - demonstrating that the key to success is collegial support and collaboration.”

Professor Róisín Owens from Cambridge’s Department of Chemical Engineering and Biotechnology, and Professor Melinda Duer from the Yusuf Hamied Department of Chemistry, were also named winners in 2020. Owens has chosen to pass her award to Professor Natalie Stingelin from Georgia Institute of Technology, and Duer has chosen to pass her award to Dr Mary Anti Chama from the University of Ghana.

“Natalie is a tremendous advocate for diversity in science and engineering,” said Owens. “She was incredibly supportive of me when I started out, mentoring me and suggesting my name for conferences and editorial work. She has worked tirelessly to support women and is very active on social media. She has brought countless young researchers, especially women under her wing, helping them to develop their careers. She is also very proactive in getting the old guard to be inclusive and diverse – including calling out conference organisers for not including women in their speaker lists. In her role as editor at RSC she has been very involved in trying to improve diversity and equality in publishing also.”

“I have known Mary since she was a Cambridge-Africa Research Fellow in Cambridge,” said Duer. “She impressed me then with how she approached interdisciplinary science, and brought in whatever techniques she needed in her quest to find new pharmaceutical compounds in plants. She has continued to impress me as she has developed her science and brought in new collaborators. She has been a champion for women in science throughout her career and very supportive of students and younger colleagues alike. I hope she won't mind my saying that she also ensured that all her siblings had access to higher education - and now continues that with ensuring that her graduate students have what they need to be successful. I always enjoy any discussion with Mary - she has shown me how one can be kind, compassionate and still be ambitious in one's science.”

Suffrage Science pioneer Professor Fisher said: “We dreamed up the awards scheme to celebrate the contribution that women have made to science, which often gets overlooked. This is as important now as it was ten years ago. This year’s awardees join a community of over 148 women scientists. I’m thrilled that since 2011, the awards have travelled from the UK, across Europe to the USA, Hong Kong, Iran and to Ghana, illustrating the international nature of science and engineering, and the global effort to improve the representation of women in STEM.”

The study, funded by Cancer Research UK, showed that before becoming cancerous, breast cells with the BRCA1 gene mutation undergo changes similar to those normally seen in late pregnancy.

Although this is early research, in the future doctors could screen women with BRCA1 mutations to monitor changes to their breast cells, which could help inform who might benefit from preventative surgery, and to give reassurance to those who can wait.

BRCA1 mutations significantly increase the risk of developing breast cancer at a younger age. Many women who discover they carry the faulty gene choose to have a preventative mastectomy. This involves surgically removing some or all of the healthy breast tissue, which can reduce but not eradicate the risk of developing breast cancer.

Not all women who have BRCA1 mutations will go on to develop cancer so for some, this life-changing surgery may be unnecessary, or could at least be delayed until early warning signs are spotted.

Researchers led by Karsten Bach and Dr Sara Pensa at the University of Cambridge wanted to develop a method to detect the early changes occurring in BRCA1-affected breast cells indicating that they are progressing towards breast cancer.  

The team analysed the mammary tissue of 15 mice at various ages carrying the BRCA1 mutation to look for changes in the tissue that were happening before the mice developed tumours.

The researchers found that having a BRCA1 mutation triggered certain pathways to be switched on in a type of stem cell called a luminal progenitor breast cell that are only activated during pregnancy. These messages tell the progenitor cell to turn into alveolar cells, which make up the chambers in the breast where milk-production takes place during late pregnancy.

Karsten Bach, co-author on the study and PhD student at the Department of Pharmacology and Cancer Research UK Cambridge Institute, said: “We thought we’d been given the wrong mice at first. Then we realised that having the BRCA1 mutation seemed to cause the cells in their breast tissue to behave as if the mouse was pregnant.

“The changes we saw happened very early on before any tumours were detected, so we reasoned that markers of these cellular changes could be used to monitor people who we know are at increased risk for breast cancer.”

Next the team analysed breast cells from 12 women who had a BRCA1 mutation and had undergone a preventative mastectomy.

Surprisingly, the team found that only 4 out of the 12 women had detectable levels of these markers of early stages of tumour initiation. This suggests that the majority of women may have been at lower risk of already being on the path towards tumour development when they had the surgery.

Dr Sara Pensa co-author and Senior Research Associate at the Department of Pharmacology and Wellcome-MRC Stem Cell Institute, said: “One of the mysteries surrounding BRCA gene mutations is how they increase a woman's risk of cancer so dramatically in the breast tissue, as opposed to say the kidneys or lung. It seems that certain pathways in breast cells that are usually switched on by hormones during pregnancy are triggered by BRCA1 mutations and cause the cells to grow out of control.”

Although this is early work and larger clinical trials will be needed, the researchers hope to build on their findings and develop a blood test to detect the early changes occurring in BRCA1 breast cells.

Researchers say in the future, doctors could screen at-risk women with BRCA1 mutations, and help them have informed conversations with women about their risk, guide decisions about preventative surgery, and to give reassurance to those considered not to need surgery at that time.

Michelle Mitchell, chief executive for Cancer Research UK, said: “The discovery of BRCA mutations gave much needed answers to families with a strong history of breast cancer. However, for women that carry the BRCA mutation that are yet to develop breast cancer, they face an incredibly difficult dilemma.  

“This is fascinating research, and we look forward to seeing the next steps, which could mean in the future, doctors could detect if women carrying these mutations have breast cells that are behaving differently. This could make a world of difference, as they may not need preventative surgery until later in life, or even at all.”

Reference

Bach K. & Pensa S. et al.'Time-resolved single-cell analysis of Brca1 associated mammary tumourigenesis reveals aberrant differentiation of luminal progenitors.' Nature Communications, March 2021.

Original press release by Cancer Research UK (CRUK).

The results, published today in the journal Microbial Genomics, provide evidence of the important role played by the movement of horses in spreading this disease, providing new opportunities for interventions that will prevent future outbreaks.

Strangles, caused by the bacteria Streptococcus equi, is the most frequently diagnosed infectious disease of horses, with 600 outbreaks estimated to occur in the United Kingdom each year.

Streptococcus equi invades the lymph nodes of head and neck of horses, causing them to swell and form abscesses that can, in around 2% of cases, literally strangle the horse to death. Some of the horses that recover from strangles remain persistently infected. These apparently healthy animals shed bacteria into the environment and spread the disease to other horses that they come into contact with.

Using standard diagnostic testing, the Streptococcus equi strains look almost identical. But by carefully examining the DNA of the bacteria, the team were able to track different variants as they spread across the world.

The research used the new online Pathogenwatch resource, developed at the Wellcome Sanger Institute, to visualise and share genome data to track the course of infections.

“Piecing the puzzle together, we showed that cases in Argentina, the United Kingdom and the United Arab Emirates were closely linked. Along with other examples, we provide evidence that the global trade and movement of horses is helping to spread the disease,” said Professor Matthew Holden of the University of St Andrews, who was involved in the study.

"This study shows once again the power of genomic data to uncover the fine detail of pathogen transmission locally and globally,” said Professor Julian Parkhill in the University of Cambridge’s Department of Veterinary Medicine, who was involved in the study.

He added: “Using whole genome sequences we can track the movement of pathogens with very high precision, showing how and where to intervene to prevent the disease spreading."

Strangles was first described in Medieval times and, with the exception of Iceland, affects horses in all corners of the world. The freedom from this disease enjoyed by Iceland is by virtue of a ban on the import of horses, which has been in place for over 1,000 years.

“This has been an incredible team effort, which was only possible through the collaboration of leading researchers from twenty-nine different scientific institutes in eighteen countries” said Dr Andrew Waller of Intervacc AB.

Horses are transported all over the world as they move to new premises or attend competitions and events. New cases of Strangles can be prevented by treating carriers before they pass on the bacteria.

Reference

Mitchell, C. et al. 'Globetrotting strangles: the unbridled national and international transmission of Streptococcus equi between horses.' Microbial Genomics, March 2021.

Collaborating Institutes

Argentina: Clinica Equina, Buenos Aires

Australia: University of Melbourne

Belgium: Ghent University, Merelbeke

France: LABÉO Frank Duncombe, Caen

Germany: Labor Dr. Böse GmbH, Harsum

Ireland: Irish Equine Centre, Naas; University College Dublin

Israel: Kimron Veterinary Institute, Bet Dagan

Italy: University of Camerino

Japan: Japan Racing Association, Tochigi

Poland: Institute of Veterinary Medicine, Warsaw University of Life Sciences - SGGW

New Zealand: Massey University, Palmerston North; University of Waikato, Hamilton

Saudi Arabia: Al Khalediah Equine Hospital, Riyadh

Spain: Exopol, Zaragoza; Universidad Complutense, Madrid

Sweden: Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala; Intervacc AB, Stockholm

The Netherlands: Royal GD, Deventer

United Arab Emirates: Central Veterinary Research Laboratory, Dubai; Emirates Racing Authority, Dubai

United Kingdom: Animal Health Trust, Newmarket; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford; Centre for Genomic Pathogen Surveillance, Wellcome Trust Sanger Institute, Cambridge; Redwings Horse Sanctuary; University of Cambridge; University of St Andrews

United States of America: Gluck Equine Research Center, Lexington; Weatherford Equine Medical Centre, Texas

Adapted from a press release by Intervacc.

The Entopia Building, a retrofitted 1930s Telephone Exchange at 1 Regent Street, Cambridge, will be transformed over the next 10 months into an ultra-low carbon sustainability hub, and new home for CISL as it scales up business, government and academic leadership, collaboration and innovation to accelerate the inclusive global transition.

The building will house CISL’s Cambridge-based staff, currently spread across five buildings, and provide a dynamic virtual hub for its offices in Brussels and Cape Town, partner organisations in China, Australia and the UAE, its global corporate partners, alumni, fellows, associates, researchers and visiting academics.

A dedicated Accelerator and Sustainability Hub will support small businesses and start-ups via collaborations, capacity building and knowledge transfer between industry experts, researchers, and major companies.

The Entopia Building is the vision of CISL Founder Director Dame Polly Courtice who has led the Institute for more than 30 years - inspiring companies, policymakers and civil society leaders to take leadership for sustainability.

Dame Polly Courtice, Founder Director, CISL said: “CISL’s new HQ at The Entopia Building will exemplify and enable our mission to support and inspire the leadership and innovation we need to transition to sustainable economy. Our aim is to create a highly collaborative and sustainable workspace to bring together Cambridge’s academic and innovation communities with our network of companies and sustainability leaders to accelerate solutions to global sustainability challenges.”

The Entopia Building aims to be an international exemplar for sustainable office retrofits, demonstrating how an existing office building can be made highly energy efficient in its redevelopment and use, while supporting the enhanced wellbeing of staff and visitors. The building will also provide a base for the Institute’s digital learning programmes which reach more than 4,000 executives each year through remote learning. High tech video conferencing facilities and collaborative digital platforms will enable its network of 16,000 alumni, fellows and associates to collaborate and engage with its work remotely.

In 2019 the University of Cambridge became the first university in the world to adopt a 1.5 degrees Science Based Target for carbon reduction, committing itself to reduce its energy-related carbon emissions to absolute zero by 2048, with an ambition to achieve this by 2038 - a decade early. In 2020 the University announced it aims to divest from all direct and indirect investments in fossil fuels by 2030 as part of its ambition to cut greenhouse gas emissions across its investment portfolio by 2038.

Professor Stephen Toope, Vice-Chancellor of the University of Cambridge said: “The Entopia Building will become the most sustainable premises in the University of Cambridge estate, marking a major contribution to our world-leading target to eliminate our emissions and putting the wellbeing of its occupants – and wider society - at its heart.”

The £12.8m retrofit has been supported by a £6m donation from green tech leaders Envision Group and a £3m grant from the European Regional Development fund (ERDF), which is also funding the operation of a sustainability hub and small business and start-up accelerator for three years. The University has invested its own funds in the project alongside an internal grant from its internal Energy & Carbon Reduction Project.

The building name references the Entopia concept developed by Envision Group to shape a future where access to clean, secure and affordable energy is available to all.

Lei Zhang, Founder and CEO, Envision Group said: “Envision Energy is pleased to support the University of Cambridge in making the Institute for Sustainability Leadership’s new headquarters an exemplar sustainability retrofit of international importance. We hope this project will lead others to be bolder in pursuing the goal of net zero as they invest in upgrading the world’s buildings and infrastructure.”

Eighty percent of UK buildings that will exist in 2050 have already been built, so although it is easier to develop new properties with high sustainability credentials, a major challenge for societies will be to retrofit existing building stock to meet climate change targets, and ensure they are fit for purpose in the future.

As a world-first, The Entopia Building aims to achieve multiple sustainable building certifications, including BREEAM (Outstanding), the Passivhaus ‘Enerphit’ standard, Well (Gold) certification, alongside the application of ‘circular economy’ principles to minimise the volume and impact of natural and made-made resources used in the building.

The project brief was developed by CISL’s Professor John French, who previously led the design and build of the award-winning Enterprise Centre at the University of East Anglia, which is demonstrably one of the most sustainable office buildings in the UK. The Entopia Building aims to open to staff by the end of 2021.

Prof. John French, Senior Advisor, CISL said: “Delivering the vision of The Entopia Building project is only possible through leadership and collaboration that puts sustainability objectives top of the list of priorities, and constantly innovates to achieve it, while not compromising cost, quality or timeline. We hope this building will provide an exemplar for the built environment, as the world moves to meet its Paris Agreement ambition to limit global warming to 1.5C.”

Sustainability benchmarks for The Entopia Building:

• The deep green retrofit is projected to result in an 80% saving in whole-life carbon emissions (over 10,000 kg CO2e), compared to a standard office refurbishment.

• The retrofit will be carried out according to EnerPHit, the Passivhaus standard for refurbishment and one of the most stringent standards for energy retrofits. It will deliver 75% lower heating demand in comparison to an average office building, and airtightness at more than five times that required by building regulations.

• The Entopia Building is on track to gain world-leading sustainability and wellbeing certification from BREEAM (Outstanding) and the WELL Building Standard (Gold).

• The project is one of the first to reuse lighting from another building refurbishment, re-testing and re- warrantying more than 350 LED lights that were then reinstalled in The Entopia Building.

• Leftover furniture in the building has been diverted from landfill, avoiding 21,000 kg of CO2, with 21,600 kg of chairs, tables and storage cabinets donated to local communities. A third of the building’s paint needs have been covered by a donation from Dulux of paint made from 35% recycled paint content.

The project is being delivered through the University’s Estates Division by a team of leading sustainability-focused firms in the architectural, main contractor, project management and engineering disciplines, who understand the need for deep collaboration and innovation to achieve stretching sustainability targets.

CISL intends to share the case study of the exemplar high sustainability retrofit project for use in the wider building sector, both within and outside higher education. In this way, The Entopia Building will contribute to CISL’s mission to develop and provide leadership for a sustainable economy, paving the way for wider change in how buildings are commissioned, managed and delivered to align with global and local sustainability ambitions.

Alexander Reeve, Sustainable Building Advisor, Estates Division, University of Cambridge said: “The project is an exciting pathfinder project for the University Estate, as we refine our strategy to eliminate fossil natural gas as a fuel for our many older buildings. It demonstrates that there is a way to transition to low carbon heating while conserving Cambridge’s outstanding built heritage.”

Adapted from a CISL press release.