The team, involving 20 researchers from seven countries, used long-range drones kitted out with a range of lightweight sensors to study the Manam volcano - one of the most active volcanoes in Papua New Guinea.

Their findings, published in the journal Science Advances, show how combined measurements from the air, earth and space can be used to understand volcanic contributions to the global carbon cycle, key to sustaining life on Earth.

One of the best ways to detect signs of an impending eruption is to ‘breathalyze’ a volcano by taking regular measurements of volcanic gases. Any change in the ratio of sulfur and carbon dioxide released can warn of an impending eruption. But sampling more remote or hazardous volcanoes like Manam is more challenging.  

When the volcano last erupted between 2004 and 2006 the entire island was evacuated - crops were destroyed and water supplies contaminated. The islanders only started to return five years ago.

Previous studies have shown that Manam is one of the world’s biggest emitters of sulphur dioxide, but nothing was known of its CO₂ output.

Measuring volcanic CO₂ emissions is more challenging because it is already present in high concentrations in the atmosphere. The only way to get accurate readings is to take samples from close to active vents. 

Collecting samples on Manam would be incredibly risky - not only is the vent flanked by precarious slopes, the volcano is also unmonitored so there would be little warning if an eruption struck.

Using drones equipped with miniaturised gas sensors, spectrometers and sampling devices the team piloted flights right into the plume emerging from Manam’s vent. The measurements captured gas composition, temperature and humidity in real-time.

The project - Aerial-Based Observations of Volcanic Emissions (ABOVE) – saw the first global collaboration between scientists, remote-sensing specialists, engineers and pilots.

Project lead Dr Emma Liu of University College London, who carried out the research while based at Cambridge’s Department of Earth Sciences, said: “these aerial measurements are pushing the frontiers of the current state-of-the-art in volcano monitoring - from the existing satellite data we know that Manam is a significant source of volcanic emissions, but that data came with a lot of uncertainty because it was measured at a distance.

“The resources of the in-country volcano monitoring institute are small and the team has an incredible workload, but they really helped us make the links with the community living on Manam island.”

Following the fieldwork, the researchers raised funds to buy computers, solar panels and other technology to enable the local community – who have since put together a disaster preparedness group - to communicate via satellite from the island, and to provide drone operations training to Rabaul Volcanological Observatory staff to assist in their monitoring efforts.

ABOVE was part of the Deep Carbon Observatory (DCO), a global community of scientists on a ten-year quest to understand more about carbon in Earth.

“Volcanic emissions are a critical stage of the Earth’s carbon cycle - the movement of carbon between land, atmosphere, and ocean – but CO₂ measurements have so far been limited to a relatively small number of the world’s estimated 500 degassing volcanoes,” said co-author Professor Marie Edmonds, also from Cambridge's Department of Earth Sciences. “Aerial gas measurements, collected along transects through the plume, together with ground-based and satellite data show that Manam is a major volcanic emission source on a global scale, which ranks fifth in terms of its carbon flux.”

Co-author Professor Alessandro Aiuppa (University of Palermo) described the findings as ‘a real advance in our field’, adding: “Ten years ago you could have only stared and guessed what Manam’s CO₂ emissions were.

“If you take into account all the carbon released by global volcanism, it’s less than a percent of the total emission budget, which is dominated by human activity. In a few centuries, humans are acting like thousands of volcanoes. If we continue to pump carbon into the atmosphere, it will make monitoring and forecasting eruptions using aerial gas observations even harder.”

“In order to understand the drivers of climate change you need to understand the carbon cycle in the Earth,” said co-author Professor Tobias Fischer from the University of New Mexico. “We wanted to quantify the carbon emission from this very large carbon dioxide emitter. We had very few data in terms of carbon isotope composition, which would identify the source of the carbon and whether it is the mantle, crust or sediment. We wanted to know where that carbon comes from.”

“Drones are changing not only the way we monitor volcanoes – they also help us to understand what causes eruptions, and how carbon moves between the Earth’s interior and atmosphere,” said Edmonds. “If we know how volcanic emissions interacted with the climate in the past, we are closer to understanding controls on our present-day climate and how it may respond to future human-driven impacts.”

ABOVE was funded by Alfred P. Solan Foundation

Reference:
E.J. Liu et al. ‘Aerial strategies advance volcanic gas measurements at inaccessible, strongly degassing volcanoes.’ Science Advances (2020). DOI: 10.1126/sciadv.abb9103.

The research, conducted by scientists at the University of Cambridge and the Institut Pasteur, was published today in the leading journal Nature. It highlights how large COVID-19 outbreaks in European nursing homes, and the potential for missing deaths in some Asian and South American countries, have skewed COVID-19 death data for older age groups, rendering cross-country comparisons of the scale of the pandemic inaccurate.

The researchers say that reporting of deaths from COVID-19 among those under the age of 65 is likely to be far more reliable, and can therefore give clearer insights into the underlying transmission of the virus and enable better comparisons between countries – crucial in guiding government strategies to try to get COVID-19 under control. 

“Simply comparing the total number of deaths across countries can be misleading as a representation of the underlying level of transmission of SARS-CoV-2. Most deaths are in older people, but they are the least comparable across countries,” said Megan O’Driscoll, a PhD researcher in the University of Cambridge’s Department of Genetics and first author of the paper.

In countries including the UK, Canada and Sweden, the COVID-19 pandemic has disproportionately affected nursing home residents, who account for over 20% of all reported COVID-19 deaths. The level of SARS-CoV-2 transmission among the general population can be difficult to disentangle from these large outbreaks. 

By contrast, some countries in Asia and South America have far fewer reported COVID-19 deaths in older people than expected. One potential explanation for these ‘missing deaths’ is that causes of deaths in elderly populations may be less likely to be investigated and reported as countries struggle to contain the epidemic.

“Nursing homes are enclosed communities of people, and once the virus gets in it can spread quickly resulting in higher levels of infection than in the general population. We’re seeing an excessively large number of deaths from COVID-19 in this older age group, particularly in countries that have many nursing homes,” said Dr Henrik Salje in the University of Cambridge’s Department of Genetics, the senior author of the report.

He added: “It’s not just that residents are older than the general population, they are also generally more frail, so a 70-year old living in a nursing home is often more likely to die of COVID-19 than a 70-year old in the general population. To reduce the overall number of COVID-19 deaths it is vital to protect vulnerable elderly communities.” 

In their new model, the researchers integrated age-specific COVID-19 death data from 45 countries with 22 national-level seroprevalence surveys. Governments of many countries are using seroprevalence surveys to estimate the number of people in a population with antibodies against the coronavirus. Antibodies indicate if a person has been infected with SARS-CoV-2 at some point, so are a good indicator of population-wide infection rates. 

“Our model shows that the number of COVID-19 deaths by age, in people under 65 years old, is highly consistent across countries and likely to be a reliable indicator of the number of infections in the population. This is of critical use in a context where most infections are unobserved,” said O’Driscoll.

The model can be used at a country-wide level to predict a person’s likelihood of dying from COVID-19 following infection, depending on their age. It also works in reverse, to estimate a country’s total number of infections given its number of COVID-19 deaths in an age group, which is particularly useful in places where seroprevalence studies have not been conducted.

Using death data from under-65 age groups only, which is most representative of transmission in the whole population, it shows that by the 1 September this year an average of 5% of the population of a country had been infected with SARS-CoV-2. However, in some places it was much higher, especially South America. 

For example, using Peru’s COVID-19 death figures, which equate to 0.01% of the country’s population, the model suggests that over half of the population of Peru has now been infected with SARS-CoV-2 – a figure far higher than expected. This indicates particularly high rates of transmission of the virus in Peru.

But even after excluding data from the over 65’s, the model shows that COVID-19 death rates cannot be compared between some countries, because the relationship between infections and deaths is not consistent when other widespread ‘co-morbidity’ factors are involved.

“It seems that people living in places such as Slovenia and Denmark have a low probability of death following infection with SARS-CoV-2, even after accounting for the ages of their populations, which is very different to what we’ve seen in New York, for example. There are likely to be fundamental differences in the populations across countries, which might include their underlying health,” said Salje.

The model also revealed a strong pattern across countries in the 5-9 year age group, which consistently has the lowest probability of death following SARS-CoV-2 infection.

The work demonstrates how age-specific death data alone can be used to reconstruct the underlying level of SARS-CoV-2 infection in a country and how it has changed over time. The researchers say this approach could be applied at sub-national scale, and may be of particular use in settings where large seroprevalence studies might not be feasible.

This research was funded by the University of Cambridge COVID-19 Rapid Response Grant.

Reference
O’Driscoll, M. et al: ‘Age-specific mortality and immunity patterns of SARS-CoV-2.’ Nature, Nov 2020. DOI: 10.1038/s41586-020-2918-0

How you can support Cambridge’s COVID-19 research

HFpEF – pronounced ‘heff peff’ – is a condition whereby heart muscles are too stiff, preventing the organ’s chambers from filling properly with blood. Symptoms include shortness of breath, swelling in the legs, ankles, feet or in the lower back or abdomen, and extreme tiredness. It affects half of the 920,000 people in the UK with heart failure but frequently goes undiagnosed.

The National Institute of Clinical Excellence (NICE) recommends that ‘integrated’ care should be provided for HFpEF, bringing together specialist clinicians with GPs and primary care, and including support for patients to help them manage their condition.

In a new study published today in the British Journal of General Practice, the researchers argue that the problems they have identified may help to explain why the condition is difficult to diagnose and why there is a persistent gap between the national guidance on managing the condition and the kind of service patients receive.

The problems were uncovered in a study carried out in the East of England, Greater Manchester and the West Midlands, in which 50 people with HFpEF, nine carers and 73 clinicians, were interviewed. The clinicians included GPs and nurses from 26 GP practices, as well as heart failure specialist nurses and cardiologists from nine hospitals.

The team used a theoretical framework known as Normalisation Process Theory to make sense of the large amount of data generated by the interviews. The theory considers how healthcare interventions are integrated into routine practice, or ‘normalised’.

For any intervention to be routinely adopted, there needs to be a clear understanding – and differentiation between – aspects of the illness, tests and treatments, for example. The team found that this understanding is often missing for the clinicians dealing with patients experiencing HFpEF. In addition, some patients described how they were not aware they had the condition despite severe symptoms and, in some cases, multiple hospital admissions, and were unclear on how the condition can be best managed.

The data confirmed that diagnosis and treatment of HFpEF is not part of everyday practice in general practice, and that the condition was not widely visible, understood, or diagnosed within primary care. The researchers identified three clear tensions that contributed to this.

First, diagnosis of HFpEF is difficult and often delayed. A common method for identifying heart disorders is through the use of an echocardiogram, but in patients with HFpEF, the ‘ejection fraction’ – the percentage of blood leaving the heart each time it contracts – often appears normal or almost normal, confusing diagnosis. Many clinicians indicated a need for specialist opinion but referral systems were varied and inconsistent.

Patients’ descriptions of their diagnoses frequently conveyed a convoluted and protracted series of hospital admissions or visits to specialist clinics. Diagnosis was often slowed down by the presence of other co-existing health conditions, non-specific symptoms and breathlessness.

Second, there are varying perceptions of this complex condition and the data show little shared understanding between clinicians, patients and carers. Several clinicians indicated there is professional scepticism with the label of HFpEF, and most expressed a need for more knowledge and understanding of the condition.

Many patients had partial or incomplete knowledge of the condition, which often related to existing heart problems. Few patients provided a clear understanding of their heart failure.

Finally, once patients are diagnosed, the services they can access are variable. Roles and responsibilities are not well understood and there are big gaps in care. A sense of clinical inertia was revealed within some patient and clinician accounts, apparently due to a lack of evidence-based practice and a feeling that there was little that could be done.

“Our research paints a picture of a cloud of clinical uncertainty surrounding the diagnosis and treatment of HFpEF, which often leads to a failure to manage the condition,” said lead author Dr Emma Sowden from the University of Manchester. “Patients’ descriptions of their diagnoses suggest they are far more convoluted than the clinical guidelines spell out, leading to a protracted series of hospital admissions or specialist visits.”

Professor Christi Deaton, Chief Investigator from the Department of Public Health and Primary Care at the University of Cambridge and a Fellow at Wolfson College, added: “We heard some clinicians asking: what’s the point of diagnosis if there is no specific treatment? But identification of HFpEF is critical if we are going to develop new treatments and ways for patients to better manage their condition, and there are actions that we can take now.”

The study is part of a larger programme of work on HFpEF, which aims to improve the management of people with HFpEF in primary care. The programme is funded by the NIHR School for Primary Care Research.

Reference
Sowden, E et al. Understanding the management of Heart Failure with Preserved Ejection Fraction: a qualitative multi-perspective study. BJGP; 3 Nov 2020; DOI: 10.3399/bjgp20X713477

Rustat, a courtier to Charles II, derived great wealth from the Royal African Company, which was responsible for shipping more enslaved Africans to the Americas than any other institution during the period of the slave trade.

In 1667, Rustat gave the University Library its first endowment, £1000, to be spent on books of its choosing. Rustat was much later memorialised by a small late 19th-century stone statue overlooking West Court at The Old Schools, the original site of the Library.

The University’s Advisory Group on the Legacies of Enslavement was asked by Vice-Chancellor Professor Stephen J Toope to make recommendations on the future of the Rustat statue. In parallel, the University Library gave consideration to the Rustat endowment, which generates income of around £5000 a year.

No decision has been made regarding the statue, but preliminary enquiries are being made about the process for removing the statue from the exterior of a Grade 1 listed building.

The Library is currently determining how income from this Rustat Fund might be remodelled (and renamed) in order to support active research into the slave trade and its legacies. For the 2020-21 financial year, income from the Fund will be spent on resources about the transatlantic slave trade and about the Black diaspora. Possible purchases will be identified collaboratively by library staff and researchers and final decisions will be taken by the Library’s Decolonisation Working Group.

Dr Jessica Gardner, Cambridge University Librarian, said: “The devastation caused by the Atlantic slave trade continues to affect millions of people globally to this day. We cannot effectively demonstrate solidarity with our black colleagues and students at Cambridge – and with others around the world – without first examining and understanding how we as an institution have benefitted from the proceeds of slavery.

“As well as asking the Inquiry to look into the Rustat benefaction, we also want to determine, with the critical help of our colleagues from the BAME community at Cambridge, how the income generated by this historic donation is best dispersed going forward.”

Jesus College has also announced that it has decided to make changes wherever Rustat is explicitly celebrated in College, following recommendations from the College’s own Legacy of Slavery Working Party.

An initial report from the University’s Advisory Group on Legacies of Enslavement was issued in May. A final report is due in Easter Term 2022.

‘A Service of Remembrance and Reconciliation for County, City, and University’, will include a blend of pre-recorded videos and live streaming from the church in Senate House Hill. It will be held in advance of the 2-minute silence at 11am, and can be accessed via YouTube here.

The Vicar of Great St Mary’s, the Reverend Canon Adrian Daffern, will lead the service which will also feature readings by the Vice-Chancellor of the University of Cambridge, Professor Stephen Toope, and the Mayor of Cambridge, Councillor Russ McPherson.

Prayers will be led by the Lord-Lieutenant of Cambridgeshire, Mrs Julie Spence OBE QPM.

Reverend Canon Adrian Daffern said: “The complexities of our present age can so easily overwhelm us. Taking time to remember the sacrifices made by millions in the past is more important than ever, if we are to learn the lessons of history, and build a peaceable future.”

The brain is arguably the most important organ in the body, as it controls most other body systems and enables reasoning, intelligence, and emotion. Humans have evolved a variety of protective measures to prevent physical damage to the brain: it sits in a solid, bony case – the skull – and is wrapped in three layers of watertight tissue known as the meninges. 

What has been less clear is how the body defends the brain from infection. Elsewhere in the body, if bacteria or viruses enter the bloodstream, our immune system kicks in, with immune cells and antibodies that target and eliminate the invader. However, the meninges form an impermeable barrier preventing these immune cells from entering the brain.

In research published today in Nature, a team led by scientists at the University of Cambridge, UK, and the National Institute of Health, USA, have found that the meninges are home to immune cells known as plasma cells, which secrete antibodies. These cells are specifically positioned next to large blood vessels running within the meninges allowing them to secrete their antibody ‘guards’ to defend the perimeter of the brain. When the researchers looked at the specific type of antibody produced by these cells, they got a surprise – the antibody they observed is normally the type found in the intestine.

Plasma cells are derived from a particular type of immune cell known as a B cell. Every B cell has an antibody on its surface that is unique to that cell. If an antigen (the part of a bacterium or virus that triggers an immune response) binds to that surface antibody, the B cell becomes activated: it will divide to make new offspring that also recognise that same antigen.

During division, the B cell introduces a mutation into the antibody gene so that one amino acid is changed and its binding characteristics are slightly different. Some of these B cells will now produce antibodies that enable better binding to the pathogen – these go on to expand and multiply; B cells whose antibodies are less good at binding die off. This helps ensure the body produces the best antibodies for targeting and destroying particular antigens.

Normally, the antibodies found in the blood are a type known as Immunoglobulin G (IgG), which are produced in the spleen and bone marrow – these antibodies protect the inside of the body. However, the antibodies found in the meninges were Immunoglobulin A (IgA), which are usually made in the gut lining or in the lining of the nose or lungs – these protect mucosal surfaces, the surfaces that interface with the outside environment.

The team were able to sequence the antibody genes in B cells and plasma cells in the gut and meninges and show that they were related. In other words, the cells that end up in the meninges are those that have been selectively expanded in the gut, where they have recognised particular pathogens.

“The exact way in which the brain protects itself from infection, beyond the physical barrier of the meninges, has been something of a mystery, but to find that an important line of defence starts in the gut was quite a surprise,” said lead scientist Professor Menna Clatworthy from the Department of Medicine and CITIID at the University of Cambridge and the Wellcome Sanger Institute.

“But actually, it makes perfect sense: even a minor breach of the intestinal barrier will allow bugs to enter the blood stream, with devastating consequences if they’re able to spread into the brain. Seeding the meninges with antibody-producing cells that are selected to recognise gut microbes ensures defence against the most likely invaders.”

The team made the discovery using mice, which are commonly used to study physiology as they share many characteristics similar to those found in the human body. They showed that when the mice had no bacteria in their gut, the IgA-producing cells in the meninges were absent, showing that these cells actually originate in the intestine where they are selected to recognise gut microbes before taking up residence in the meninges. When the researchers removed the plasma cells in the meninges – and hence no IgA was present to trap bugs – microbes were able to spread from the bloodstream into the brain.

The team confirmed the presence of IgA cells in the human meninges by analysing samples that were removed during surgery, showing that this defence system is likely to play an important role in defending humans from infections of the central nervous system – meningitis and encephalitis.

Professor Clatworthy is a Fellow of Pembroke College.

Reference
Fitzpatrick, Z et al. Gut-educated IgA plasma cells defend the meningeal venous sinuses. Nature; 4 Nov 2020; DOI: 10.1038/s41586-020-2886-4

Image
Confocal micrograph showing the superior saggital sinus (a dural venous sinus) in the mouse. Immune cells are shown in green lining this tube, and blood vessels in red. (Credit: Zach Fitzpatrick)

A team of researchers, led by the University of Cambridge, have identified a new mechanism of targeting amyloid-beta, a protein fragment that clumps together and kills healthy brain cells in people with Alzheimer’s disease.

Working with colleagues from Imperial College London, Institut Pasteur, and the University of Florence, the researchers found that it is possible for a drug-like molecule to target amyloid-beta in its disordered state, reducing its ability to form the toxic clusters which are the hallmark of Alzheimer’s disease. The results, reported in the journal Science Advances, could form the basis of a new avenue for the development of potential treatments for the disease.

“Amyloid-beta is a disordered protein, a type of target that is elusive for standard therapeutic approaches,” said Professor Michele Vendruscolo from Cambridge’s Centre for Misfolding Diseases, who led the research. “It is constantly changing shape, so traditional drug discovery techniques don’t work on it. By revealing a new drug-binding mechanism, we have extended traditional drug discovery approaches based on the optimisation of the binding affinity to include disordered proteins.”

Most drugs work by binding proteins through what is often described as a lock-and-key mechanism, where a drug fits into a protein’s grooves like a key in a lock. However, since they are often changing shape, disordered proteins such as amyloid-beta don’t have stable ‘locks’ for drugs to bind to, which is why they are considered ‘undruggable.’

The approach developed by the researchers is based on the so-called disordered binding mechanism that they discovered, where small molecules form a disordered complex with the protein target, so that it is like the protein and the drug are ‘dancing’ with one another.

The researchers characterised this new mechanism using a combination of biophysical experiments, mathematical modelling, in vivo experiments and computation.

First, they tested the aggregation of amyloid-beta in the presence of the compound in in vitro assays. Data from these experiments allowed the researchers to build a mathematical model of how the drug was able to inhibit the aggregation of amyloid-beta at the microscopic level.

The team also used high-performance computing methods to study the binding interaction at the atomic level. These intensive calculations allowed the researchers to ‘see’ how the binding was occurring at the atomic level, which is otherwise almost impossible to observe experimentally. Further tests were then carried out in nematode worms, which are often used as a model organism to study Alzheimer’s disease.

“In contrast to the traditional lock-and-key binding mechanism, in which a drug tightly interacts with its target in a specific conformation, we found that both the small molecule and the disordered protein remained extremely dynamic, and that the small molecule interacted with many parts of the protein,” said Gabriella Heller, Schmidt Science Fellow and the study’s first author.

“This way of stabilising native states of proteins is a powerful drug discovery strategy, which has so far been extremely challenging for disordered proteins,” said Vendruscolo.

Amyloid beta, the protein which the team targeted, is closely associated with Alzheimer’s disease as it is the primary component of senile plaques, which are characteristically found in the brains of the people affected by the disease.

While this research is still preliminary in terms of clinical translation, it demonstrates that targeting the formation of these plaques by preventing the aggregation of amyloid-beta is a major therapeutic strategy. To date the mainstream approach has been to develop antibodies to bind to the aggregates, promoting their removal and interfering with their self-assembly.

“Disordered proteins are also involved in a wide range of diseases including cancer and cardiovascular disease. We hope that we can extend this understanding to also target disordered proteins involved in other diseases,” said Heller.

Reference:
Gabriella T. Heller et al. ‘Small-molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer’s disease.’ Science Advances (2020). DOI: 10.1126/sciadv.abb5924

Axons – nerve fibres – in the adult central nervous system (CNS) do not normally regenerate after injury and disease, meaning that damage is often irreversible. However, over the past decade there have been a number of discoveries that suggest it may be possible to stimulate regeneration.

In a study published today in Nature Communications, scientists tested whether the gene responsible for the production of a protein known as Protrudin could stimulate the regeneration of nerve cells and protect them from cell death after an injury.

The team, led by Dr Richard Eva, Professor Keith Martin and Professor James Fawcett from the John van Geest Centre for Brain Repair at the University of Cambridge, used a cell culture system to grow brain cells in a dish. They then injured their axons using a laser and analysed the response to this injury using live-cell microscopy. The researchers found that increasing the amount or activity of Protrudin in these nerve cells vastly increased their ability to regenerate. 

Nerve cells in the retina, known as retinal ganglion cells, extend their axons from the eye to the brain through the optic nerve in order to relay and process visual information. To investigate whether Protrudin might stimulate repair in the injured CNS in an intact organism, the researchers used a gene therapy technique to increase the amount and activity of Protrudin in the eye and optic nerve. When they measured the amount of regeneration a few weeks after a crush injury to the optic nerve, the team found that Protrudin had enabled the axons to regenerate over large distances. They also found that the retinal ganglion cells were protected from cell death.

The researchers showed that this technique may help protect against glaucoma, a common eye condition. In glaucoma, the optic nerve that connects the eye to the brain is progressively damaged, often in association with elevated pressure inside the eye. If not diagnosed early enough, glaucoma can lead to loss of vision. In the UK, round one in 50 people over the age of 40, and one in ten people over the age of 75 is affected by glaucoma.

To demonstrate this protective effect of Protrudin against glaucoma, the researchers used a whole retina from a mouse eye and grew it in a cell-culture dish. Usually around a half of retinal neurons die within three days of retinal removal, but the researchers found that increasing or activating Protrudin led to almost complete protection of retinal neurons.

Dr Veselina Petrova from the Department of Clinical Neurosciences at the University of Cambridge, the study’s first author, said: “Glaucoma is one of leading causes of blindness worldwide. The causes of glaucoma are not completely understood, but there is currently a large focus on identifying new treatments by preventing nerve cells in the retina from dying, as well as trying to repair vision loss through the regeneration of diseased axons through the optic nerve.

“Our strategy relies on using gene therapy – an approach already in clinical use – to deliver Protrudin into the eye. It’s possible our treatment could be further developed as a way of protecting retinal neurons from death, as well as stimulating their axons to regrow. It’s important to point out that these findings would need further research to see if they could be developed into effective treatments for humans.”

Protrudin normally resides within the endoplasmic reticulum, tiny structures within our cells. In this study, the team showed that the endoplasmic reticulum found in axons appears to provide materials and other cellular structures important for growth and survival in order to support the process of regeneration after injury. Protrudin stimulates transport of these materials to the site of injury.

Dr Petrova added: “Nerve cells in the central nervous system lose the ability to regenerate their axons as they mature, so have very limited capacity for regrowth. This means that injuries to the brain, spinal cord and optic nerve have life-altering consequences.

“The optic nerve injury model is often used to investigate new treatments for stimulating CNS axon regeneration, and treatments identified this way often show promise in the injured spinal cord. It’s possible that increased or activated Protrudin might be used to boost regeneration in the injured spinal cord.”

The research was supported by the Medical Research Council, Fight for Sight, the Bill and Melinda Gates Foundation, Cambridge Eye Trust and the National Eye Research Council.

Reference
Petrova, V et al. Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS. Nat Comms; 5 Nov 2020; DOI: 10.1038/s41467-020-19436-y

SARS-CoV-2 is one of many coronaviruses. All share the characteristic of having the largest single-stranded RNA genome in nature. This genome contains all the genetic code the virus needs to produce proteins, evade the immune system and replicate inside the human body. Much of that information is contained in the 3D structure adopted by this RNA genome when it infects cells.  

The researchers say most current work to find drugs and vaccines for COVID-19 is focused on targeting the proteins of the virus. Because the shape of the RNA molecule is critical to its function, targeting the RNA directly with drugs to disrupt its structure would block the lifecycle and stop the virus replicating.

In a study published today in the journal Molecular Cell, the team uncovered the entire structure of the SARS-CoV-2 genome inside the host cell, revealing a network of RNA-RNA interactions spanning very long sections of the genome. Different functional parts along the genome need to work together despite the great distance between them, and the new structural data shows how this is accomplished to enable the coronavirus life cycle and cause disease.

“The RNA genome of coronaviruses is about three times bigger than an average viral RNA genome – it’s huge,” said lead author Dr Omer Ziv at the University of Cambridge’s Wellcome Trust/Cancer Research UK Gurdon Institute.

He added: “Researchers previously proposed that long-distance interactions along coronavirus genomes are critical for their replication and for producing the viral proteins, but until recently we didn’t have the right tools to map these interactions in full. Now that we understand this network of connectivity, we can start designing ways to target it effectively with therapeutics.”

In all cells the genome holds the code for the production of specific proteins, which are made when a molecular machine called a ribosome runs along the RNA reading the code until a ‘stop sign’ tells it to terminate. In coronaviruses, there is a special spot where the ribosome only stops 50% of the times in front of the stop sign. In the other 50% of cases, a unique RNA shape makes the ribosome jump over the stop sign and produce additional viral proteins. By mapping this RNA structure and the long-range interactions involved, the new research uncovers the strategies by which coronaviruses produce their proteins to manipulate our cells. 

“We show that interactions occur between sections of the SARS-CoV-2 RNA that are very long distances apart, and we can monitor these interactions as they occur during early SARS-CoV-2 replication,” said Dr Lyudmila Shalamova, a co-lead investigator at Justus-Liebig University, Germany.

Dr Jon Price, a postdoctoral associate at the Gurdon Institute and co-lead of this study, has developed a free, open-access interactive website hosting the entire RNA structure of SARS-CoV-2. This will enable researchers world-wide to use the new data in the development of drugs to target specific regions of the virus’s RNA genome.

The genome of most human viruses is made of RNA rather than DNA. Ziv developed methods to investigate such long-range interactions across viral RNA genomes inside the host cells, in work to understand the Zika virus genome. This has proved a valuable methodological basis for understanding SARS-CoV-2. Ziv is now planning to set up an independent research group to study the genomes of emerging pathogens, in the University of Cambridge’s Department of Biochemistry.

This research is a collaborative study between the group of Professor Eric Miska at the University of Cambridge’s Gurdon Institute and Department of Genetics, and the group of Professor Friedemann Weber from the Institute for Virology, Justus-Liebig University, Gießen, Germany. It was funded by Cancer Research UK, Wellcome, and Deutsche Forschungsgemeinschaft (DFG). 

Ziv explains the research finding in this short video:

Reference
Ziv, O. et al: ‘The short- and long-range RNA-RNA Interactome of SARS-CoV-2.’ Mol Cell, November 2020. DOI: 10.1016/j.molcel.2020.11.004

How you can support Cambridge’s COVID-19 research

Professor Dr M Osman Babury
Chancellor
Kabul University

By email

4 November 2020

Dear Professor Babury,

I read with shock and grave concern about the terrible events at Kabul University this week. May I offer the sincere condolences of everyone at the University of Cambridge at the appalling loss of life resulting from this attack.

I believe that Higher Education, with its capacity to work across borders to tackle some of the great global challenges, is a force for good in an uncertain world. An attack on a university is an attack on the future and a grave assault on all that we at Cambridge hold dear.

As you face the task of rebuilding and renewing your educational mission, please know that you have the good wishes and support of friends in universities around the world.

With best wishes,

Professor Stephen J Toope

Vice-Chancellor
University of Cambridge

The free-to-play Harmony Square is released to the public today, along with a study on its effectiveness published in the Harvard Misinformation Review.

It has been created by University of Cambridge psychologists with support from the US Department of State's Global Engagement Center and Department of Homeland Security Cybersecurity and Infrastructure Security Agency (CISA).

The gameplay is based on “inoculation theory”: that exposing people to a weak “dose” of common techniques used to spread fake news allows them to better identify and disregard misinformation when they encounter it in future.

In this case, by understanding how to incite political division in the game using everything from bots and conspiracies to fake experts, players get a form of “psychological vaccine” against the product of these techniques in the real world.    

“Trying to debunk misinformation after it has spread is like shutting the barn door after the horse has bolted. By pre-bunking, we aim to stop the spread of fake news in the first place,” said Dr Sander van der Linden, Director of the Cambridge Social Decision-Making lab and senior author of the new study.

Twitter has started using a “pre-bunk” approach: highlighting types of fake news likely to be encountered in feeds during the US election. However, researchers argue that familiarising people with techniques behind misinformation builds a “general inoculation”, reducing the need to rebut each individual conspiracy.

In the 10-minute game Harmony Square, a small town neighbourhood “obsessed with democracy” comes under fire as players bait the square’s “living statute”, spread falsehoods about its candidate for “bear controller”, and set up a disreputable online news site to attack the local TV anchor.

“The game itself is quick, easy and tongue-in-cheek, but the experiential learning that underpins it means that people are more likely to spot misinformation, and less likely to share it, next time they log on to Facebook or YouTube,” said Dr Jon Roozenbeek, a Cambridge psychologist and lead author of the study.

Over the course of four short levels, users learn about five manipulation techniques: trolling to provoke outrage; exploiting emotional language to create anger and fear; artificially amplifying reach through bots and fake followers; creating and spreading conspiracy theories; polarizing audiences.

In a randomised controlled trial, researchers took 681 people and asked them to rate the reliability of a series of news and social media posts: some real, some misinformation, and even some faked misinformation created for the study, in case participants had already come across real-world examples.

They gave roughly half the sample Harmony Square to play, while the other half played Tetris, and then asked them to rate another series of news posts.

The perceived reliability of misinformation dropped an average of 16% in those who completed Harmony Square compared to their assessment prior to playing. The game also reduced willingness to share fake news with others by 11%. Importantly, the players’ own politics – whether they leaned left or right – made no difference. 

Having the “control group” who played Tetris allowed the scientists to determine an “effect size” of 0.54 for the study, said Van der Linden.

“The effect size suggests that if the population was split equally like the study sample, 63% of the half that played the game would go on to find misinformation significantly less reliable, compared to just 37% of the half left to navigate online information without the inoculation of Harmony Square,” he said.

The project follows other playful attempts by CISA to illustrate how “foreign influencers” use disinformation to target “hot button” issues. A previous demonstration took the example of whether pineapple belongs on pizza.

However, Harmony Square is based on the findings of a number of studies from the Cambridge team showing how similar gamified approaches to digital literacy significantly reduce susceptibility to fake news and online conspiracies.  

The team behind the game, which includes the Dutch media agency DROG and designers Gusmanson, have recently worked with the UK Cabinet Office on Go Viral!, an intervention that specifically tackles conspiracies around COVID-19.

Harmony Square is geared towards the politically charged misinformation that has plagued many democracies over the last decade. “The aftermath of this week’s election day is likely to see an explosion of dangerous online falsehoods as tensions reach fever pitch,” said van der Linden. 

“Fake news and online conspiracies will continue to chip away at the democratic process until we take seriously the need to improve digital media literacy across populations. The effectiveness of interventions such as Harmony Square are a promising start,” he said.

The University of Cambridge kicks off its first global Climate Change Festival today (6 November), the first of eight days of free online climate-themed events for all ages.

Cambridge Zero, the University’s climate initiative, has partnered with the academic publishing powerhouse Cambridge University Press to offer a week of live panel sessions, pre-recorded talks demonstrations, stories and games, led by leading thinkers from science, academia, policy and community groups from around the world.

The Festival will start this afternoon with a preview of “A Blueprint for a Green Future,” Cambridge Zero’s report on the necessary policy changes needed build a sustainable future, which will be launched next week. The Director of Cambridge Zero, Dr Emily Shuckburgh, and some of the report’s authors will be discussing how to ensure a green recovery from the COVID-19 pandemic and mitigate the worst effects of climate change.

The Festival will also include live talks and panel sessions with leaders in the climate movement including scientist, TV personality and best-selling author Dr Emily Grossman; British environmentalist and writer Sir Jonathan Porritt; US Under Secretary for Science Paul M Dabbar and Australian Indigenous scholar and writer Tyson Yunkaporta.  

The Festival takes place at the time when the UN Climate Change Conference (COP26) was due to take place in Glasgow, which has been postponed to 2021 due to the pandemic.

The eight days of online events, both live and on-demand, will cover the five themes of COP26: Energy Transitions, Zero Carbon Transport, Finance, Adaptation & Resilience, and Nature, along with a sixth theme of Green Recovery. Each of the eight days also covers one of the UN’s Sustainable Development Goals (SDGs).

University of Cambridge Vice-Chancellor Stephen J. Toope said: “This Climate Change Festival offers us optimism in the midst of a global crisis. By sparking collaboration and dialogue between the academic and non-academic communities, it will help us focus on what we can all achieve together, and shine a light on some of the solutions already being implemented locally, nationally and internationally. Taking place at the time when COP26 would have happened, it is a testimony to our commitment to tackling the global climate crisis.”

Director of Cambridge Zero, Dr Emily Shuckburgh OBE said: “This is the moment to reset our priorities and to re-evaluate our relationships with each other and with the world that sustains us. This Festival is a chance for us to share some of the exciting research and new initiatives underway at Cambridge Zero, and beyond, to show how we all can make a difference and live more sustainably.”

All sessions are free to join with recordings made available to watch again on Cambridge Open Engage, the research and collaboration platform developed by Cambridge University Press.

To learn more about the festival, view the programme and register for events, visit the festival website, or follow @CambridgeZero on Twitter, Instagram, LinkedIn and Facebook.

The study, published today in the journal Nature Communications, analysed changes in the geographical range of 16,919 species from 1700 to the present day. The data were also used to predict future changes up to the year 2100 under 16 different climate and socio-economic scenarios. 

A diverse abundance of species underpins essential ecosystem functions from pest regulation to carbon storage. Species’ vulnerability to extinction is strongly impacted by their geographical range size, and devising effective conservation strategies requires a better understanding of how ranges have changed in the past, and how they will change under alternative future scenarios.

“The habitat size of almost all known birds, mammals and amphibians is shrinking, primarily because of land conversion by humans as we continue to expand our agricultural and urban areas,” said Dr Robert Beyer in the University of Cambridge’s Department of Zoology, first author of the report.

Some species are more heavily impacted than others. A worrying 16% of species have lost over half their estimated natural historical range, a figure that could rise to 26% by the end of the century. 

Species’ geographical ranges were found to have recently shrunk most significantly in tropical areas. Until around 50 years ago, most agricultural development was in Europe and North America. Since then, large areas of land have been converted for agriculture in the tropics: clearance of rainforest for oil palm plantations in South East Asia, and for pasture land in South America, for example.

As humans move their activities deeper into the tropics, the effect on species ranges is becoming disproportionately larger because of a greater species richness in these areas, and because the natural ranges of these species are smaller to begin with.

“The tropics are biodiversity hotspots with lots of small-range species. If one hectare of tropical forest is converted to agricultural land, a lot more species lose larger proportions of their home than in places like Europe,” said Beyer.

The results predict that climate change will have an increasing impact on species’ geographical ranges. Rising temperatures and changing rainfall patterns will alter habitats significantly, for example: other studies have predicted that without climate action, large parts of the Amazon may change from canopy rainforest to a savannah-like mix of woodland and open grassland in the next 100 years. 

“Species in the Amazon have adapted to living in a tropical rainforest. If climate change causes this ecosystem to change, many of those species won’t be able to survive - or they will at least be pushed into smaller areas of remaining rainforest,” said Beyer.

He added: “We found that the higher the carbon emissions, the worse it gets for most species in terms of habitat loss.” 

The results provide quantitative support for policy measures aiming at limiting the global area of agricultural land – for example by sustainably intensifying food production, encouraging dietary shifts towards eating less meat, and stabilising population growth. 

The conversion of natural vegetation to agricultural and urban land, and the transformation of suitable habitat caused by climate change are major causes of the decline in range sizes, and two of the most important threats to global terrestrial biodiversity.

“Whether these past trends in habitat range losses will reverse, continue, or accelerate will depend on future global carbon emissions and societal choices in the coming years and decades,” Professor Andrea Manica in the University of Cambridge’s Department of Zoology, who led the study.

He added: “While our study quantifies the drastic consequences for species’ ranges if global land use and climate change are left unchecked, they also demonstrate the tremendous potential of timely and concerted policy action for halting - and indeed partially reversing - previous trends in global range contractions. It all depends on what we do next.”

This research was supported by the European Research Council. 

Reference
Beyer, R.M. & Manica, A.: ‘Historical and projected future range sizes of the world’s mammals, birds and amphibians.’ Nature Communications, Nov 2020. DOI: 10.1038/s41467-020-19455-9

The IHRA definition is a useful tool for understanding how antisemitism manifests itself in our society. It will be used as a test to establish whether behaviour that is in breach of the University’s rules is anti-Semitic.

The IHRA definition is as follows:

“Antisemitism is a certain perception of Jews, which may be expressed as hatred toward Jews. Rhetorical and physical manifestations of antisemitism are directed toward Jewish or non-Jewish individuals and/or their property, toward Jewish community institutions and religious facilities.”

“Contemporary examples of antisemitism in public life, the media, schools, the workplace, and in the religious sphere could, taking into account the overall context, include, but are not limited to:

• Calling for, aiding, or justifying the killing or harming of Jews in the name of a radical ideology or an extremist view of religion.
• Making mendacious, dehumanizing, demonizing, or stereotypical allegations about Jews as such or the power of Jews as collective — such as, especially but not exclusively, the myth about a world Jewish conspiracy or of Jews controlling the media, economy, government or other societal institutions.
• Accusing Jews as a people of being responsible for real or imagined wrongdoing committed by a single Jewish person or group, or even for acts committed by non-Jews.
• Denying the fact, scope, mechanisms (e.g. gas chambers) or intentionality of the genocide of the Jewish people at the hands of National Socialist Germany and its supporters and accomplices during World War II (the Holocaust).
• Accusing the Jews as a people, or Israel as a state, of inventing or exaggerating the Holocaust.
• Accusing Jewish citizens of being more loyal to Israel, or to the alleged priorities of Jews worldwide, than to the interests of their own nations.
• Denying the Jewish people their right to self-determination, e.g., by claiming that the existence of a State of Israel is a racist endeavor.
• Applying double standards by requiring of it a behavior not expected or demanded of any other democratic nation.
• Using the symbols and images associated with classic antisemitism (e.g., claims of Jews killing Jesus or blood libel) to characterize Israel or Israelis.
• Drawing comparisons of contemporary Israeli policy to that of the Nazis.
• Holding Jews collectively responsible for actions of the state of Israel.”

The University has also included the following clarifications “to ensure that freedom of speech is maintained in the context of discourse about Israel and Palestine, without allowing antisemitism to permeate any debate”, as recommended by the Home Affairs Select Committee:

• “It is not anti-Semitic to criticise the government of Israel, without additional evidence to suggest anti-Semitic intent  
• It is not anti-Semitic to hold the Israeli government to the same standards as other liberal democracies, or to take a particular interest in the Israeli government's policies or actions, without additional evidence to suggest anti-Semitic intent.”  

Having seen a large rise in illegal transactions during the first national lockdown last spring, the researchers will warn at a workshop this afternoon that the second lockdown is likely to result in another surge in cybercrime activities. But they will also be offering insights on how such activity can be disrupted.

The researchers have been collecting the data on illicit trades from HackForums – the world’s largest and most popular online cybercrime community. Two years ago, it set up a market where contracts had to be logged for all transactions as an attempt to protect members of the community from scamming and frauds.

The contract system was introduced in 2018, and then made mandatory in spring 2019, for all market users. It logged all the illicit buying and selling of – among other things – malicious software (malware), currencies including Bitcoin and gift vouchers, eWhoring ‘packs’ (e.g. of photos and videos with sexual content), hacking tutorials and tools that allow users illegally to access or control remote servers.   

Ironically, HackForums had introduced the contract logging system in response to its members’ concerns that trades were being abused and they were being scammed. But in doing so, it unwittingly lifted the lid on the way such underground markets operate.

The data the contract logging generated has been collected by researchers here. And after analysing it and using statistical modelling approaches, the researchers have been able to shed important new light on the way a cybercrime market operates, hopefully to the benefit of the security community.

The researchers watched the market initially function as a forum where many individual users conducted one-off transactions. Then it changed. As the contract system became mandatory, within a few months, the market was becoming concentrated around a small group of ‘power-users’ offering goods and services that were attractive to many.

“This small group of users – representing about 5 per cent of all users – are involved in around 70 per cent of all the transactions,” said Anh Vu, a research assistant in the Cambridge Cybercrime Centre and co-author of the paper the Centre has just produced, ‘Turning Up the Dial: the Evolution of a Cybercrime Market through Set-up, Stable, and Covid-19 Eras’ .

And then came the global declaration of the coronavirus pandemic in March 2020. The research team saw the virus and the resulting lockdowns that were introduced significantly “turn up the dial” on the number of market transactions.

“There was a big rise in transactions in what we call the ‘Covid-19 era’,” said Anh. “Looking at the discussion forums, we could see that a period of mass boredom and economic change – when presumably some members were not able to go to school and others had lost their jobs – really stimulated the market.

“Members needed to make money online and they had a lot of time on their hands, and so we saw a rise in trading activity. We expect to see another rise during the second lockdown, but we don’t think it will be as large as during the first.”

The increase in business during the pandemic also meant that contracts for transactions were concluded much faster. Where in the early months of the market, the completion time for contracts was around 70 hours, during the pandemic it dropped to less than 10 hours.

Online underground forums like HackForums are communities used for trading in illicit material and sharing knowledge. The forums support a plethora of cybercrimes, allowing members to learn about and engage in criminal activities such as trading virtual items obtained by illicit means, launching denial of service attacks, or obtaining and using malware. They facilitate a variety of illicit businesses aiming at making easy money.

The Cambridge Cybercrime Centre researchers have done some previous work looking at underground forums. “But this is the first dataset we are aware of that provides insights about the contracts made in these forums,” says Anh. Previously, while traders might meet online in a forum, they would likely trade offline via private messaging. But the introduction of the contract system means all trades are now logged – and can therefore be tracked.

Using the data, the researchers looked at a variety of trading activities taking place in the market. The largest activities were currency exchanges and payments – for example, exchanging Bitcoin (a very popular currency in illicit trading because people believe that it leaves no trace) for PayPal funds.

This activity was followed by trades in gift cards (including Amazon gift cards) and software licences. “When you install a software package like Windows,” Anh said. “You have to input a key to activate it. People often buy software keys illegally in a market like this because it is cheaper for them than purchasing it officially from Microsoft – and sometimes they can obtain it for free in exchange for other items.”

Other products and services they found being traded in the underground market were hacking tutorials, remote access tools and eWhoring materials – photos and videos with sexual content that are sold to a third party, who pays for them believing that they are paying for an online sexual encounter.

They used several methods to try and estimate the values of trades taking place via HackForums and concluded that taking both public and private transactions into account and extrapolating by each contract type, the lower bound total of trades was in excess of $6 million.

What the researchers learned about the operation of an underground cybercrime market is valuable, they believe, to the security community. The logging of contracts when goods were traded has allowed users to build up a form of trust and reputation and this in turn led to the rise of the ‘power-users’ in the market.

“And now we know a small group of power-users are responsible for a large number of transactions, it would make sense to focus interventions on them,” Anh said. “As that will have a much bigger impact than going after a large number of individuals.”

In their paper they suggest interventions to undermine the perceived reputations and trustworthiness of the big players – for example by posting false negative reviews of them and using other methods, known as Sybil attacks, that disrupt the market’s reputation systems.

And the researchers are continuing to watch the market. “We’re interested to know how the marketplace evolves during this second lockdown and afterwards,” said Anh. “And will be looking to see whether any new trading activities emerge.”

Reference: 
‘Turning Up the Dial: the Evolution of a Cybercrime Market through Set-up, Stable, and Covid-19 Eras’ was presented at a seminar series of the 2020 Internet Measurement Conference. It was also presented at the Workshop on Security and Human Behaviour taking place on Thursday 5 November 2020.

Mongooses rarely leave the group they are born into, so members are usually genetically related. The new study, published today in the journal Proceedings of the National Academy of Sciences, reveals how females get around the problem of inbreeding.

The research team, led by the University of Cambridge and the University of Exeter, say ‘exploitative leadership’ of this kind, which is also seen in human warfare, leads to frequent and damaging conflicts.

"Female banded mongooses start fights between groups to gain genetic benefits from mating with outsiders, while the males within their group – and the group as a whole – pay the costs,” said Professor Michael Cant, at the Centre for Ecology and Conservation on Exeter’s Penryn Campus in Cornwall, who was involved in the research.

He added: "A classic explanation for warfare in human societies is leadership by exploitative individuals who reap the benefits of conflict while avoiding the costs.

"In this study, we show that leadership of this kind can also explain the evolution of severe collective violence in certain animal societies."

Dr Faye Thompson at the University of Exeter, and senior author of the report, added: "The findings do not fit a heroic model of leadership, in which leaders contribute most to aggression and bear greatest costs, but rather an exploitative model, in which the initiators of conflict expose others to greater risks while contributing little to fighting themselves."

The findings suggest that decoupling leaders from the costs of their choices amplifies the destructive nature of intergroup conflict.

Professor Rufus Johnstone from the University of Cambridge’s Department of Zoology and first author of the report, said: "Exploitative leadership in banded mongooses helps to explain why intergroup violence is so costly in this species compared to other animals.

"The mortality costs involved are similar to those seen in a handful of the most warlike mammals, including lions, chimpanzees - and of course humans."

The study used long-term data from wild banded mongooses in Uganda.

Reference

Johnstone, R.A. et al; “Exploitative leaders incite intergroup warfare in a social mammal." Proceedings of the National Academy of Sciences, Nov 2020. DOI: 10.1073/pnas.2003745117

Adapted from a press release by the University of Exeter.

The Universe Unravelledseries premieres on Discovery+ in November 2020, coinciding with the UK launch of this new digital platform. The series is aimed at anyone who is curious about the Universe we live in, with no previous knowledge of cosmology required. Across more than 20 short episodes, the series explores what we already know about the Universe, what cosmologists and relativists are working on right now, and where new observations may lead in the future.

The programme is inspired by the late Stephen Hawking’s ground-breaking work on cosmology, black holes and gravitational waves, and features researchers from the Hawking Centre for Theoretical Cosmology (CTC) and the Kavli Institute for Cosmology at the University of Cambridge.

The series explores the big questions in contemporary research which are being driven by new observations, such as the recent discovery of gravitational waves. It starts with Einstein’s general theory of relativity, describing how massive objects warp the fabric of spacetime and how they can collapse under their own gravity to form black holes. It explores how these black holes can send gravitational waves rippling across spacetime, and what happens if you were to fall into a black hole.

The series also describes the violent explosion that marked the beginning of our Universe, and how the Universe expanded from this initial Big Bang, forming all the structures we observe today – galaxies, stars and planets. It then probes the mysteries that still puzzle cosmologists, such as dark energy and dark matter. The series ends with a future outlook of what we might expect to learn from ambitious new observational programmes. All the basic concepts underlying are presented in an easily accessible manner, and it features stunning graphics, some produced in collaboration with Intel’s Advanced Visualization team.

The series features CTC and Kavli researchers explaining these remarkable concepts. It offers a glimpse of what it’s like to work at the cutting edge of cosmology: confronting sophisticated mathematics with observational data, employing some of the world’s fastest supercomputers, and even daring to challenge Einstein's highly successful theory in an attempt to explain what has so far defied explanation. Viewers not only learn about the deepest secrets of our Universe, but also find out about the everyday life of students and staff at a world-leading research centre.

The collaboration between Discovery and the CTC started in 2010. A highlight was Discovery live-streaming Stephen Hawking's 75th birthday symposium which was a huge success watched by millions, especially among younger members of their audience.

The series was filmed at the Centre for Mathematical Sciences and the Institute of Astronomy and produced with the help of science editors from Plus magazine, part of the University’s Millennium Mathematics Project outreach programme.

The CTC team worked closely with Navada Studios, who were responsible for the video production, with editorial oversight from Discovery producers. Funding for the project was provided by the Kavli Foundation, an organisation dedicated to advancing science for the benefit of humanity, promoting public understanding of scientific research, and supporting scientists and their work.

“We are grateful to Discovery and the Kavli Foundation for supporting this unique opportunity to continue Stephen Hawking’s vision of reaching out, especially to younger audiences, to inspire curiosity about our Universe and the huge progress currently being made to unveil its secrets,” said Paul Shellard, CTC Director. “This was a remarkable collaboration in which we were able to work closely with the production team, ensuring both viewer interest and scientific accuracy, which we hope provides a great model for future science outreach.”

The series is available on the new Discovery+ service that can be found at discoveryplus.co.uk, together with a short trailer. To find out more about the Hawking Centre, visit ctc.cam.ac.uk.

The app uses computer vision techniques to read and record the glucose levels, time and date displayed on a typical glucose test via the camera on a mobile phone. The technology, which doesn’t require an internet or Bluetooth connection, works for any type of glucose meter, in any orientation and in a variety of light levels. It also reduces waste by eliminating the need to replace high-quality non-Bluetooth meters, making it a cost-effective solution to the NHS.

Working with UK glucose testing company GlucoRx, the Cambridge researchers have developed the technology into a free mobile phone app, called GlucoRx Vision, which is now available on the Apple App Store and Google Play Store.

To use the app, users simply take a picture of their glucose meter and the results are automatically read and recorded, allowing much easier monitoring of blood glucose levels.

In addition to the glucose meters which people with diabetes use on a daily basis, many other types of digital meters are used in the medical and industrial sectors. However, many of these meters still do not have wireless connectivity, so connecting them to phone tracking apps often requires manual input.

“These meters work perfectly well, so we don’t want them sent to landfill just because they don’t have wireless connectivity,” said Dr James Charles from Cambridge’s Department of Engineering. “We wanted to find a way to retrofit them in an inexpensive and environmentally-friendly way using a mobile phone app.”

In addition to his interest in solving the challenge from an engineering point of view, Charles also had a personal interest in the problem. He has type 1 diabetes and needs to take as many as ten glucose readings per day. Each reading is then manually entered into a tracking app to help determine how much insulin he needs to regulate his blood glucose levels.

“From a purely selfish point of view, this was something I really wanted to develop,” he said.

“We wanted something that was efficient, quick and easy to use,” said Professor Roberto Cipolla, also from the Department of Engineering. “Diabetes can affect eyesight or even lead to blindness, so we needed the app to be easy to use for those with reduced vision.”

The computer vision technology behind the GlucoRx app is made up of two steps. First, the screen of the glucose meter is detected. The researchers used a single training image and augmented it with random backgrounds, particularly backgrounds with people. This helps ensure the system is robust when the user’s face is reflected in the phone’s screen.

Second, a neural network called LeDigit detects each digit on the screen and reads it. The network is trained with computer-generated synthetic data, avoiding the need for labour-intensive labelling of data which is commonly needed to train a neural network.

“Since the font on these meters is digital, it’s easy to train the neural network to recognise lots of different inputs and synthesise the data,” said Charles. “This makes it highly efficient to run on a mobile phone.”

“It doesn’t matter which orientation the meter is in – we tested it in all types of orientations, viewpoints and light levels,” said Cipolla, who is also a Fellow of Jesus College. “The app will vibrate when it’s read the information, so you get a clear signal when you’ve done it correctly. The system is accurate across a range of different types of meters, with read accuracies close to 100%”

In addition to blood glucose monitor, the researchers also tested their system on different types of digital meters, such as blood pressure monitors, kitchen and bathroom scales. The researchers also recently presented their results at the 31^st British Machine Vision Conference.

Gluco-Rx initially approached Cipolla’s team in 2018 to develop a cost-effective and environmentally-friendly solution to the problem of non-connected glucose meters, and once the technology had been shown to be sufficiently robust, the company worked with the Cambridge researchers to develop the app.

“We have been working in partnership with Cambridge University on this unique solution, which will help change the management of diabetes for years to come,” said Chris Chapman, Chief Operating Officer of GlucoRx. “We will soon make this solution available to all of our more than 250,000 patients.”

As for Charles, who has been using the app to track his glucose levels, he said it “makes the whole process easier. I’ve now forgotten what it was like to enter the values in manually, but I do know I wouldn’t want to go back to it. There are a few areas in the system which could still be made even better, but all in all I’m very happy with the outcome.”

Reference:
James Charles, Stefano Bucciarelli and Roberto Cipolla. ‘Real-time screen reading: reducing domain shift for one-shot learning.’ Paper presented at the British Machine Vision Conference: https://bmvc2020-conference.com/conference/papers/paper_0512.html

The COVID-19 pandemic has plunged us all into a state of uncertainty. In a rapidly changing situation where it is hard to know what will happen next, making decisions can be difficult. Researchers at the University of Cambridge and University College London created a simplistic model of this uncertain situation in the lab, to understand how our brain responds.

They found that when situations seem stable, we tend to rely on our on previous experiences to help us anticipate what will happen in the future. But when the world is volatile, our brain can let go of these expectations and allow rapid learning. The balance between the two approaches is moderated by the brain chemical noradrenaline. The study is published today in the journal Current Biology. 

“Adapting to uncertain situations helps us to survive. When something unexpected happens, we have to decide whether it’s a one-off and ignore it, or whether it’s going to keep happening – in which case we might benefit by doing things differently,” said Dr Rebecca Lawson, a researcher in the University of Cambridge’s Department of Psychology and lead author of the study.

The study tested the effects of Propranolol - a drug used to reduce anxiety and blood pressure - on how people responded to stable situations and to changeable ones. Propranolol blocks the action of noradrenaline. 

Participants in the experiment - who were not suffering with anxiety - heard a sound and were then shown an image of either a house of a face. They quickly learned to predict the image they would see depending on the sound they heard before it appeared. The association between particular sounds and images was then changed at random intervals, increasing uncertainty and requiring participants to quickly learn new associations.

The reaction times of participants who received a placebo drug slowed down as the associations became more unexpected. Those who received Propranolol relied on the sound to a greater extent when uncertainty was high. This suggests that the drug makes people more likely to rely on their expectations, based on prior experience, in the face of uncertainty – which could be how it works to reduce feelings of anxiety.

Using a computational model, the researchers showed that the Propranolol group were slower than the placebo group at learning to use new information to adjust their expectations of what might come next, when a situation is very uncertain.

“We found that a brain chemical called noradrenaline plays a role in our inability to predict the future when the state of the world is volatile,” said Lawson.

When a situation is stable - represented in the experiment by a fixed link between sounds and images – our past experiences can be relied upon as a good guide to what will happen next. But when a situation is changing, we need to be more receptive to new information to try and work out what is happening and how to respond.

“In the face of uncertainty, people taking the anti-anxiety drug Propranolol showed an increased reliance on past experience to inform their behaviour – they were less influenced by changes in their environment that contradicted that experience,” said Lawson.

Difficulty in balancing expectations against new information is thought to underlie many conditions including autism and anxiety. The team plans to extend their research to try and understand how people with these conditions learn under uncertainty. In the longer term, this could help those with autism and anxiety to recognise the source of their anxiety and manage it better.

This research was funded by Wellcome. Dr Lawson is a Fellow of the Lister Institute and an Autistica Future Leaders Fellow.  

Reference
Lawson, R.P. et al: ‘The computational, pharmacological, and physiological determinants of sensory learning under uncertainty.’ Current Biology, November 2020. DOI: 10.1016/j.cub.2020.10.043

The additional investment will enable COG-UK to grow and strengthen current genomic surveillance efforts spearheaded by the Wellcome Sanger Institute and the University of Cambridge, together with the four UK Public Health Agencies and other COG-UK partners, with the aim of increasing sequencing capacity across the national network and reducing turnaround time from patient sample to genome sequence.

The viral genome sequencing data will be integrated within the four UK Public Health Agencies & NHS Test and Trace to help understand outbreaks and strengthen infection control measures. Integrating real-time viral genomic data into outbreaks investigations identifies patterns linking individual cases and can reveal otherwise unidentifiable opportunities for intervention. Viral genome sequencing also enables monitoring of the evolution of the virus for mutations that may impact on the efficacy of vaccines.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, represents a major threat to health. The COG-UK Consortium was created to deliver large-scale and rapid whole-genome virus sequencing to local NHS centres, Public Health Agencies and the UK government.

Led by Professor Sharon Peacock of the University of Cambridge & Director Of Science at Public Health England, COG-UK is an innovative partnership of NHS organisations, the four Public Health Agencies of the UK, the Wellcome Sanger Institute and 12 academic institutions from across the UK providing world leading expertise in SARS-CoV-2 genomics and supporting sequencing and analysis capacity nationwide.

Since its launch in March 2020, COG-UK has generated and made publicly available more than 100,000 SARS-CoV-2 genomes, making up over 45 per cent of the global total. This unprecedented effort has not been achieved previously for any pathogen, anywhere in the world.

COG-UK researchers have built a central database and developed cutting-edge analytical methodology and data pipelines for SARS-CoV-2 genomics. COG-UK has led the development of analytical software to define viral lineages and shares methods globally.

Collectively, these data and tools have provided important scientific insights into the spread and evolution of the virus, at local, regional, national and international scales.

However, the steadily rising numbers of cases in the UK requires a prompt increase in the national SARS-CoV-2 genome sequencing capacity, to ensure that the benefits of using genome sequence data can be realised in a rapid and robust manner.

Professor Sharon Peacock, who is the Director of COG-UK, Professor of Public Health and Microbiology at the University of Cambridge and a Director Of Science (Pathogen Genomics) at Public Health England, said: “To fully understand the spread and evolution of the SARS-CoV-2 virus, we must sequence and analyse the viral genomes. The pattern of accumulation of mutations in the genomes enables us to determine the relatedness of virus samples and define viral lineages in order to understand whether local outbreaks are caused by transmission of single or multiple viral lineages. Analysis of viral genome sequences also allow us to monitor the evolution of SARS-CoV-2 and assess whether specific mutations influence transmission, disease severity, or the impact of interventions such as vaccines.”

The four UK Public Health Agencies and COG-UK are working to link SARS-CoV-2 genome data with epidemiological, clinical and contact tracing records nationally. 

This will help establish a comprehensive national dataset linking viral sequencing with host genomics, immunology, clinical outcomes and risk factors.

Adapted from a press release from COG-UK