In response to the COVID-19 pandemic, the UK Government implemented a national 'lockdown' involving school closures and social distancing. There has been widespread concern that these measures would negatively impact child and adolescent mental health. To date, however, there is relatively little direct evidence of this.

The most direct way of measuring the association between the onset of lockdown and children’s mental health is to follow the same individuals over a length of time and look for changes – so-called ‘longitudinal’ changes. 

To test whether changes in emotional wellbeing, anxiety and depression symptoms occurred during lockdown since their initial assessment, a team at the Medical Research Council (MRC) Cognition and Brain Sciences Unit, University of Cambridge, examined data from mental health assessments on 168 children (aged 8-12 years) before and during the UK lockdown. These assessments included self-reports, caregiver-reports, and teacher-reports.

The results of their study are published today in Archives of Disease in Childhood.

Relative to their own pre-pandemic scores, children tended to show more symptoms of depression during lockdown. Even though these symptoms are variable across children, the impact of lockdown can still be seen because the effect size is large. The researchers used the variability in scores to estimate how big an increase this is.

“To give an indication of how large this effect is, imagine ranking the children into 100 ‘centiles’ depending on their scores,” explained Dr Duncan Astle from the MRC Cognition and Brain Sciences Unit and senior author of the study. “A child in the 50th centile would be exactly at the middle of the distribution. But a child at this position before the pandemic, could expect to be at the equivalent of the 77th centile during the lockdown.

“Put differently, if you randomly selected a child from the sample there is a 70% chance that their depression symptoms were worse during lockdown than before the pandemic.”

“National lockdowns with mass school closures are unprecedented, so going into this crisis, no one could say definitively what impact it would have on children,” said Giacomo Bignardi, a PhD student at the MRC Cognition and Brain Sciences Unit.

“Our study is one of the first to follow the same children over time during lockdown and suggests that symptoms of depression among children got much worse during this period. This effect was independent of children’s age, gender and family socio-economic status.”

The team found only very small and not statistically significant changes in children’s scores for emotional problems and anxiety during lockdown.

Dr Astle added: “Childhood is a period where mental health may be particularly vulnerable to reduced peer interaction and loneliness. Now that children have returned to school, their wellbeing, socialisation and enjoyment are crucial. Teachers may need additional resources and training to help them support children with low mood.

“Even before lockdown resources for Child and Adolescent Mental Health Services were stretched thin – and that was against a backdrop of worsening mental health among children. Our findings suggest that lockdown measures will likely exacerbate this. The education sector will bear the initial brunt of this.”

The researchers say that how the lockdown measures impact children’s mental health may depend on a variety of factors. A recent study found that loneliness in children was associated with subsequent mental health problems, particularly depression. Also, during lockdown children had fewer opportunities to engage in play and other fun activities that help improve mood.

The research was supported by the Templeton World Charity Foundation and the Medical Research Council.

Reference
Bignardi, G et al. Longitudinal increases in childhood depression symptoms during the COVID-19 lockdown. Archives of Disease in Childhood; 9 Dec 2020; DOI: 10.1136/archdischild-2020-320372

The researchers, from the University of Cambridge, have shown that microscopic particles can remain intrinsically linked, or entangled, over long distances even if there are random disruptions between them. Using the mathematics of quantum theory, they discovered a simple setup where entangled particles can be prepared and stabilised even in the presence of noise by taking advantage of a previously unknown symmetry in quantum systems.

Their results, reported in the journal Physical Review Letters, open a new window into the mysterious quantum world that could revolutionise future technology by preserving quantum effects in noisy environments, which is the single biggest hurdle for developing such technology. Harnessing this capability will be at the heart of ultrafast quantum computers.

Quantum systems are built on the peculiar behaviour of particles at the atomic level and could revolutionise the way that complex calculations are performed. While a normal computer bit is an electrical switch that can be set to either one or zero, a quantum bit, or qubit, can be set to one, zero, or both at the same time. Furthermore, when two qubits are entangled, an operation on one immediately affects the other, no matter how far apart they are. This dual state is what gives a quantum computer its power. A computer built with entangled qubits instead of normal bits could perform calculations well beyond the capacities of even the most powerful supercomputers.

“However, qubits are extremely finicky things, and the tiniest bit of noise in their environment can cause their entanglement to break,” said Dr Shovan Dutta from Cambridge’s Cavendish Laboratory, the paper’s first author. “Until we can find a way to make quantum systems more robust, their real-world applications will be limited.”

Several companies – most notably, IBM and Google – have developed working quantum computers, although so far these have been limited to less than 100 qubits. They require near-total isolation from noise, and even then, have very short lifetimes of a few microseconds. Both companies have plans to develop 1000 qubit quantum computers within the next few years, although unless the stability issues are overcome, quantum computers will not reach practical use.

Now, Dutta and his co-author Professor Nigel Cooper have discovered a robust quantum system where multiple pairs of qubits remain entangled even with a lot of noise.

They modelled an atomic system in a lattice formation, where atoms strongly interact with each other, hopping from one site of the lattice to another. The authors found if noise were added in the middle of the lattice, it didn’t affect entangled particles between left and right sides. This surprising feature results from a special type of symmetry that conserves the number of such entangled pairs.

“We weren’t expecting this stabilised type of entanglement at all,” said Dutta. “We stumbled upon this hidden symmetry, which is very rare in these noisy systems.”

They showed this hidden symmetry protects the entangled pairs and allows their number to be controlled from zero to a large maximum value. Similar conclusions can be applied to a broad class of physical systems and can be realised with already existing ingredients in experimental platforms, paving the way to controllable entanglement in a noisy environment.

“Uncontrolled environmental disturbances are bad for survival of quantum effects like entanglement, but one can learn a lot by deliberately engineering specific types of disturbances and seeing how the particles respond,” said Dutta. “We’ve shown that a simple form of disturbance can actually produce – and preserve – many entangled pairs, which is a great incentive for experimental developments in this field.”

The researchers are hoping to confirm their theoretical findings with experiments within the next year.

The research was funded in part by the Engineering and Physical Sciences Research Council (EPSRC).

Reference:
Shovan Dutta and Nigel R. Cooper. ‘Long-range coherence and multiple steady states in a lossy qubit array.’ Physical Review Letters (2020). DOI: 10.1103/PhysRevLett.125.240404

Grace 2 of 28 September 2020 and three amendments (statement on freedom of speech):

Turnout for all elections and ballots November 2020 was 32.1%.


The result can be viewed on the Cambridge University Reporter webpages

Following this ballot, the University has adopted a revised University Statement on Freedom of Speech.  

Commenting on the result of the ballot, the Vice-Chancellor, Professor Stephen J Toope, said:

"I welcome the result of the vote by the Regent House today which is an emphatic reaffirmation of free speech in our University. The University will now implement the amended statement and this marks the conclusion of the democratic decision-making process on this matter. I would like to thank my colleagues who proposed the amendments that have now been agreed by the University’s governing body. 

"Freedom of speech is a right that sits at the heart of the University. This statement is a robust defence of that right. The University will always be a place where anyone can express new ideas and controversial or unpopular opinions, and where those views can be robustly challenged. The statement also makes it clear that is unacceptable to censor, or disinvite, speakers whose views are lawful but may be seen as controversial.

"Rigorous debate is fundamental to the pursuit of academic excellence and the University of Cambridge will always be a place where freedom of speech is not only protected, but strongly encouraged."

Details of the amendments can be viewed in the Reporter.

Three hundred and twenty-seven mid-career researchers were today awarded Consolidator Grants by the ERC, totalling €655 million. The UK has 50 grantees in this year’s funding round. The funding is part of the EU’s current research and innovation programme, Horizon 2020.

The ERC Consolidator Grants are awarded to outstanding researchers of any nationality and age, with at least seven and up to 12 years of experience after PhD, and a scientific track record showing great promise.

The research projects proposed by the new grantees cover a wide range of topics in physical sciences and engineering, life sciences, as well as social sciences and humanities. 

From the University of Cambridge, the following researchers were named as grantees:

Vasco Carvalho, Professor of Macroeconomics and Director of Cambridge-INET

Project title: Micro Structure and Macro Outcomes.

Professor Tuomas Knowles of the Yusuf Hamied Department of Chemistry

Project title: Digital Protein Biophysics of Aggregation.

Dr Neel Krishnaswami of the Computer Laboratory

Project title: Foundations of Type Inference for Modern Programming Languages.

Dr Kaisey Mandel of the Institute of Astronomy and the Statistical Laboratory of the Department of Pure Mathematics and Mathematical Statistics.

Project title: Next-Generation Data-Driven Probabilistic Modelling of Type Ia Supernova SEDs in the Optical to Near-Infrared for Robust Cosmological Inference.

Professor Silvia Vignolini of the Yusuf Hamied Department of Chemistry

Project title: Sym-Bionic Matter: developing symbiotic relationships for light-matter interaction.

In a landmark phase 3 clinical trial, the international team, coordinated by Dr Patrick Yu-Wai-Man from the University of Cambridge and Dr José-Alain Sahel from the University of Pittsburgh and Institut de la Vision, Paris, successfully treated 37 patients suffering from Leber hereditary optic neuropathy (LHON). Subject to further trials, the treatment could help thousands of people across the world to regain and retain some of their sight.

The study, published today in the journal Science Translational Medicine, indicates that 78% of treated patients experienced significant visual improvement in both eyes. It suggests that the improvement in vision in untreated eyes could be due to the transfer of viral vector DNA from the injected eye.

LHON affects a specific type of retinal cells, known as retinal ganglion cells, causing optic nerve degeneration and rapidly worsening vision in both eyes. Within a few weeks of disease onset, the vision of most people affected deteriorates to levels at which they are considered legally blind. Visual recovery occurs in less than 20% of cases and few achieve vision better than 20/200 (largest letter on a standard eye chart). LHON affects approximately 1 in 30,000 people, mostly men, with symptoms usually emerging in their 20s and 30s. The majority of patients carry the m.11778G>A mutation in the MT-ND4 gene. Existing treatment for this blinding optic neuropathy remains limited.

“As someone who treats these young patients, I get very frustrated about the lack of effective therapies,” said senior investigator Dr Sahel, a professor of ophthalmology at the University of Pittsburgh. “These patients rapidly lose vision in the course of a few weeks to a couple of months. Our study provides a big hope for treating this blinding disease in young adults.”

The researchers injected rAAV2/2-ND4 – a viral vector containing modified cDNA – into the vitreous cavity at the back of one eye of 37 patients who had suffered vision loss for between 6 to 12 months. Their other eye received a sham injection. The technology, called mitochondrial targeting, was developed by the Institut de la Vision in Paris, France, and licensed to GenSight Biologics.

International coordinating investigator and neuro-ophthalmologist Dr Yu-Wai-Man, from Cambridge’s Department of Clinical Neurosciences and Moorfields Eye Hospital, London, said: “We expected vision to improve in the eyes treated with the gene therapy vector only. Rather unexpectedly, both eyes improved for 78% of patients in the trial following the same trajectory over 2 years of follow-up.” 

Treated eyes showed a mean improvement in best-corrected visual acuity (BCVA) of 15 letters on an ETDRS chart, representing three lines of vision, while a mean improvement of 13 letters was observed in the sham treated eyes. As some patients were still in the dynamic phase of the disease process upon enrolment, the visual gain from the nadir (worst BCVA for each eye) was even larger, reaching 28.5 letters for the treated eyes and 24.5 letters for sham-treated eyes.

Dr Yu-Wai-Man said: “By replacing the defective MT-ND4 gene, this treatment rescues the retinal ganglion cells from the destructive effects of the m.11778G>A mutation, preserving function and improving the patient’s visual prognosis. The outcomes can be life-changing.”

The researchers found that treated eyes were around three times more likely to achieve vision better than or equal to 20/200. Patient-reported outcome measures evaluated using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) also confirmed the positive impact of treatment on quality of life and psychosocial well-being.

The researchers then conducted a study in cynomolgus macaques to investigate how the treatment of one eye could bring about improvement in the other. Macaques have a visual system similar to that of humans, which allows the distribution and effects of the gene therapy vector to be studied in much greater detail. A unilateral injection of rAAV2/2-ND4 was administered and after three months, tissues from various parts of the eye and the brain were analysed to detect and quantify the presence of viral vector DNA using a transgene-specific quantitative PCR assay.

Viral vector DNA was detected in the anterior segment, retina and optic nerve of the untreated eye. The unexpected visual improvement observed in the untreated eyes could therefore reflect the interocular diffusion of rAAV2/2-ND4. Further investigations are needed to confirm these findings and whether other mechanisms are contributing to this bilateral improvement.

Dr Yu-Wai-Man said: “Saving sight with gene therapy is now a reality. The treatment has been shown to be safe and we are currently exploring the optimal therapeutic window.”

“Our approach isn’t just limited to vision restoration,” added Dr Sahel. “Other mitochondrial diseases could be treated using the same technology.”

Reference

Patrick Yu-Wai-Man et al., 'Bilateral Visual Improvement with Unilateral Gene Therapy Injection for Leber Hereditary Optic Neuropathy'; Science Translational Medicine (9 December 2020). DOI: 10.1126/scitranslmed.aaz7423

One in 17 UK citizens lives with a rare disease, which are defined as conditions that affect fewer than one in 2,000 people in the general population. A group of experts has written to The Lancet highlighting their concerns about the detrimental impact a no deal Brexit will have on these individuals.

“Rare diseases are rare, and experts are rarer still,” said Dr Marc Tischkowitz from the University of Cambridge, who helped coordinate the letter. “European Reference Networks were set up because no single country has the expertise or resources to cover all of the known rare diseases, which number in the thousands. They’ve played a pivotal role in harnessing the collective knowledge across the continent and in developing sustainable healthcare to treat those affected.”

The UK has been at the forefront of the creation and development of these virtual networks, which involve healthcare providers across Europe. As a result, write the experts, it has been able “to reap the benefits of closer collaboration with experts and patient advocates throughout Europe”.

The ERNs have made it much easier to develop guidelines, create disease registries, build research collaborations, and create new education and training programmes. Crucially, they have directly improved patient care by establishing a pan-European platform that brings international experts together to advise on patient-specific complex problem and therapeutic options where insufficient expertise exists in one country alone.

Dr Tischkowitz added: “Leaving the EU without an agreement on UK participation in the Networks means we potentially write off years of progress made by UK clinicians, researchers and patient advocates, while also reducing access to clinical trials and funding. Most importantly, it will diminish our ability to provide the best care for the millions of children and adults with rare diseases and complex conditions in the future.”

The letter has a total of 73 signatories, including 20 signatories each representing a patient support group and 53 signatories from senior clinicians and researchers who are currently members of a European Reference Network and who will be removed from the networks as of 1 January if no agreement is reached.

Allison Watson co-founded Ring20, a charity that supports people living with ring chromosome 20 Syndrome, an ultra-rare disease that affects her young adult son. She is also a co-lead for the EpiCARE ERN for rare and complex epilepsies.

“I have been hugely encouraged by the change that being part of an ERN can bring, for people like my son and many others living with ultra-rare diseases,” said Watson. “I believe we would not have managed this working with just UK rare disease organisations.”

Initiatives already delivered through the EpiCARE ERN include heightened awareness of rare epilepsies (including ring chromosome 20 Syndrome) across the 28 EpiCARE centres, long overdue Orphanet updates, increased information and education to healthcare practitioners and patient families in the form of leaflets and patient journeys, plus updated Clinical Practice Guidelines which aim to simplify and speed up diagnosis and improve care through understanding the unmet needs.

Watson added: “With thousands of rare diseases, many of them ultra-rare where only a handful of people living in the UK are affected, is it cost-effective or even possible that the UK can deliver effective services and research alone for these people alone? I believe only through collaboration with our European partners and others around the world can we truly meet the needs of the affected and ultimately improve their outcomes and quality of life.”

Beverley Power, chair of CDH UK, the congenital diaphragmatic hernia support charity, says that one of the main barriers to research within the field of rare diseases is access to patients and patient data.

“Since joining the ERNICA European Reference Network, the access to patients and data has become broader for the UK and the rest of Europe,” she explained. “It has enabled charities like CDH UK to better understand other healthcare settings and to be able to signpost newly diagnosed parents and patients with ongoing medical needs in a much better direction. It has also introduced new and innovative ways to collaborate in order to effect better outcomes and quality of life for patients and their families, which ultimately can potentially impact the economic implications of treating rare diseases in the UK and overseas.”

Reference
Tischkowitz, M et al. A no-deal Brexit will be detrimental to people with rare diseases. Lancet; 12 Dec 2020; DOI: 10.1016/S0140-6736(20)32631-3

Correspondence pieces represent the views of the authors and not necessarily the views of The Lancet or any Lancet specialty journal. Unlike Articles containing original research, this Correspondence was not externally peer reviewed.

The response to the COVID-19 pandemic has been hampered by the lack of effective antiviral drugs against SARS-CoV-2, the coronavirus that causes the disease. Scientists had pinned hope on the drug remdesivir, originally developed to treat hepatitis C and subsequently tested against Ebola. However, results from large clinical trials have been inconclusive, and in early October the World Health Organization (WHO) announced that the drug did not significantly reduce mortality rates. The question is more complicated, however, and a clinical team have now used a different approach to determine the effects of the drug on COVID-19 in a closely monitored patient.

Dr James Thaventhiran from the MRC Toxicology Unit at the University of Cambridge said: “There have been different studies supporting or questioning remdesivir’s effectiveness, but some of those conducted during the first wave of infection may not be optimal for assessing its antiviral properties.

“Mortality is due to a combination of factors, likely including unchecked viral replication and, importantly, the response of the immune system. A clinical trial that looks only at remdesivir’s impact on mortality will have difficulty distinguishing between these two factors. This limits our ability to ask the simple question: how good is remdesivir as an antiviral?”

To answer this question, a team led by scientists at the University of Cambridge and Barts Health NHS Trust examined the case of a 31 year old man with XLA, a rare genetic condition that affects the body's ability to produce antibodies and hence fight infection.

The patient’s illness began with fever, cough, nausea and vomiting, and on day 19 he tested positive for SARS-CoV-2. His symptoms persisted and on day 30 he was admitted to hospital, where he was given supplemental oxygen due to breathing difficulties.

Unusually, his fever and inflammation of the lungs persisted for longer than 30 days, but without causing severe breathing problems or spreading to other organs. The researchers say this may have been due to his inability to produce antibodies – although antibodies fight infection, they can also cause damage to the body and even lead to severe disease.

At first, the patient was treated with hydroxychloroquine and azithromycin, which had little effect, and the treatments were stopped on day 34. The patient then commenced a ten-day course of remdesivir. Within 36 hours, his fever and shortness of breath had improved and his nausea and vomiting ceased. Rising oxygen saturation allowed him to be taken off supplemental oxygen.

This dramatic clinical response was accompanied by a progressive decrease in levels of C-reactive protein (CRP), a substance produced by the liver in response to inflammation. At the same time, doctors saw an increase in the number of his immune cells known as lymphocytes, and chest scans showed that his lung inflammation was clearing. The patient was discharged on day 43.

A week after discharge, the patient’s fever, shortness of breath and nausea returned. He was readmitted to hospital on day 54 and given supplemental oxygen. He again tested positive for SARS-CoV-2, was found to have lung inflammation, and his CRP levels had increased and his lymphocyte count fallen.

On day 61, the patient began treatment with a further ten-day course of remdesivir. Once again, his symptoms improved rapidly, his fever dropped and he was taken off supplemental oxygen. His CRP and lymphocyte count normalised. Following additional treatment with convalescent plasma on days 69 and 70, he was discharged three days later and is no longer symptomatic.

The team found that the patient’s virus levels fell progressively during his first course of remdesivir, corresponding with the improvement in his symptoms. His virus levels increased again, as did his symptoms, when the first course of the treatment ceased, but the effect of the second course of remdesivir was even more rapid and complete. By day 64, he was no longer testing positive for the coronavirus.

The patient’s inability to clear his infection without antiviral medication is very likely to be due to his lack of antibodies, say the researchers. However, there are other immune cells that contribute to fighting infection, including those known as CD8+ T cells. The team observed that the patient was able to produce CD8+ T cells that responded to the ‘spike protein’ on the surface of the virus – spike proteins give the virus its characteristic crown profile (hence the name coronavirus). While insufficient to clear the infection spontaneously, this likely contributed to the clearance of virus during the second course of remdesivir.

Dr Nicholas Matheson from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) at the University of Cambridge added: “Our patient’s unusual condition gave us a rare insight into the effectiveness of remdesivir as a treatment for coronavirus infection. The dramatic response to the drug – on repeated challenge – suggests that it can be a highly effective treatment, at least for some patients.”

The team further suspect that remdesivir is likely to be most beneficial when administered early in infection, before the virus is able to trigger a potentially catastrophic immune response. They say that the course of their patient’s disease also underscores the important – but often conflicting – roles that antibodies play in protecting us from infection.

“The fact that our patient was unable to fight off the disease without treatment suggests that antibodies contribute to the control of SARS-CoV-2,” explained Dr Matthew Buckland from the Department of Clinical Immunology, Barts Health, London. “But this lack of antibodies may also have prevented his COVID-19 from becoming life-threatening, because he had no antibodies to trigger a damaging immune response.

“All of this suggests that treatments will need to be tailored for individual patients, depending on their underlying condition – for example, whether it is the virus that is causing the symptoms, or the immune response. The extended viral monitoring in our study was clinically necessary because in April 2020 we didn’t know if this drug would be effective. Adopting this approach more widely could further clarify how best to use remdesivir for clinical benefit.”

The research was supported by the Medical Research Council, the NIHR Bioresource, NHS Blood and Transplant, Wellcome and the European Union’s Horizon 2020 programme.

Reference
Buckland, MS et al. Successful treatment of COVID-19 with remdesivir in the absence of humoral immunity, a case report. Nat Comms; 14 Dec 2020; DOI: 10.1038/s41467-020-19761-2

Despite this very significant development, some voices in the media remain inexplicably determined to point fingers at Giulio’s supervisor, Dr Maha Abdelrahman. Press reports have rehashed old and baseless assertions that she did not cooperate with the original investigation. These are malicious and defamatory accusations, with no basis in evidence. A full account of Dr Abdelrahman’s record of collaborations with the investigators can be found in our earlier statements.

Press reports continue to misrepresent the nature of the relationship between Giulio and Dr Abdelrahman. This demonstrates a fundamental – and continued – lack of understanding about the nature of academic research, and about the intellectual relationship between PhD students and their supervisors, which is one of support, critique and advice rather than instruction. He was an experienced researcher, with experience of field work in Egypt, working on legal independent trade unions that were also being researched by many others at the time.

This latest round of misinformation has triggered unjust and unjustified vilification of an honourable scholar. It has led to harassment and threats. The reiteration of such damaging insinuations is scurrilous and irresponsible.

The University of Cambridge welcomes the move by Italian prosecutors to charge four individuals directly connected with Giulio’s disappearance, torture and death. We stand with Giulio’s family, friends and colleagues in the search for justice and truth.

Prof Stephen J Toope

Vice-Chancellor

Frontotemporal dementia is a significant cause of dementia among younger people. It is often diagnosed between the ages of 45 and 65. It changes behaviour, language and personality, leading to impulsivity, socially inappropriate behaviour, and repetitive or compulsive behaviours.

A common feature of frontotemporal dementia is apathy, with a loss of motivation, initiative and interest in things. It is not depression, or laziness, but it can be mistaken for them. Brain-scanning studies have shown that in people with frontotemporal dementia it is caused by shrinkage in special parts at the front of the brain – and the more severe the shrinkage, the worse the apathy. But, apathy can begin decades before other symptoms, and be a sign of problems to come.

“Apathy is one of the most common symptoms in patients with frontotemporal dementia. It is linked to functional decline, decreased quality of life, loss of independence and poorer survival,” said Maura Malpetti, a cognitive scientist at the Department of Clinical Neurosciences, University of Cambridge.

“The more we discover about the earliest effects of frontotemporal dementia, when people still feel well in themselves, the better we can treat symptoms and delay or even prevent the dementia.”

Frontotemporal dementia can be genetic. About a third of patients have a family history of the condition. The new discovery about the importance of early apathy comes from the Genetic Frontotemporal dementia Initiative (GENFI), a collaboration between scientists across Europe and Canada. Over 1,000 people are taking part in GENFI, from families where there is a genetic cause of Frontotemporal dementia. 

Now, in a study published today in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, Professor Rowe and colleagues have shown how apathy predicts cognitive decline even before the dementia symptoms emerge. 

The new study involved 304 healthy people who carry a faulty gene that causes frontotemporal dementia, and 296 of their relatives who have normal genes. The participants were followed over several years. None had dementia, and most people in the study did not know whether they carry a faulty gene or not. The researchers looked for changes in apathy, memory tests and MRI scans of the brain. 

“By studying people over time, rather than just taking a snapshot, we revealed how even subtle changes in apathy predicted a change in cognition, but not the other way around,” explained Malpetti, the study’s first author. "We also saw local brain shrinkage in areas that support motivation and initiative, many years before the expected onset of symptoms.”

People with the genetic mutations had more apathy than other members of their family, which over two years increased much more than in people with normal genetics.  The apathy predicted cognitive decline, and this accelerated as they approached the estimated age of onset of symptoms.

Professor Rogier Kievit from the Donders Institute, Radboud University Medical Center at Nijmegen and MRC Cognition and Brain Sciences Unit at Cambridge, said: “Apathy progresses much faster for those individuals who we know are at greater risk of developing frontotemporal dementia, and this is linked to greater atrophy in the brain. At the start, even though the participants with a genetic mutation felt well and had no symptoms, they were showing greater levels of apathy. The amount of apathy predicted cognitive problems in the years ahead.”

“From other research, we know that in patients with frontotemporal dementia, apathy is a bad sign in terms of independent living and survival. Here we show its importance in the decades before symptoms begin,” said Professor James Rowe from the Department of Clinical Neurosciences, joint senior author. 

Professor Rowe said the study highlights the importance of investigating why someone has apathy. “There are many reasons why someone feels apathetic. It may well be an easy to treat medical condition, such as low levels of thyroid hormone, or a psychiatric illness such as depression. But doctors need to keep in mind the possibility of apathy heralding a dementia, and increasing the chance of dementia if left unaddressed, particularly if someone has a family history of dementia.

“Treating dementia is a challenge, but the sooner we can diagnose the disease, the greater our window of opportunity to try and intervene and slow or stop its progress.”

The research was largely funded by the Medical Research Council, Wellcome, and the National Institute for Health Research.

Reference
Malpetti, M et al. Apathy in pre-symptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes. Alzheimer's & Dementia; 14 Dec 2020; DOI: 10.1002/alz.12252

The researchers, from the University of Cambridge, tested a variety of materials to construct a new inexpensive and reliable method for assessing the fit of masks. Commercial testing equipment has been in extremely short supply since the outbreak of the COVID-19 pandemic, forcing many healthcare institutions to abandon regular fit-testing of their staff.

Their results, published in the journal Disaster Medicine and Public Health Preparedness, found that widely-available alternatives, such as aroma diffusers and extra-large freezer bags, can be used to make a qualitative fit-testing setup which performs at a similar level to commercial solutions.

While commercial kits typically cost several hundred pounds, the Cambridge setup can be made for under £35. In addition to its potential benefits to the healthcare industry, this inexpensive setup can be used by anyone who wants to test the fit of their mask at home.

The researchers caution, however, that their setup will only test the fit of sealing masks with high filtration ability, such as N95, FFP3, KN95 or FFP2 masks. The method cannot be used to test the fit of surgical or fabric masks, as these do not typically offer the fit or filtration necessary to pass a qualitative fit-test.

Sealing masks offer the wearer a high level of protection, but only if they fit properly, with no gaps between the mask and the wearer’s face. Previous studies have found that even if the mask material is highly efficient at filtering fine particles, the effectiveness of the mask is hampered by an imperfect seal.

“So far, there has not been an inexpensive, accessible and reliable way of testing the fit of sealing masks,” said Eugenia O’Kelly from Cambridge’s Department of Engineering, the study’s first author. “Shortages of the fit-testing equipment that healthcare facilities normally use have left some of them unable to test their workers. And those who do not work in healthcare have had no reliable way to ensure their masks fit.”

Most healthcare facilities use qualitative fit-testing methods on their staff, as these are faster and cheaper than quantitative methods. Qualitative fit-testing requires three key pieces of equipment: a testing solution, a diffuser to atomise the solution, and a testing hood.

To carry out a typical fit-test, a user places the hood over their head while wearing a mask, and the solution is aerosolised into the enclosure as a fine mist. The solution is usually sweet or bitter. The fit of the mask is assessed by how well the user can taste the solution while nodding their head or speaking. If the mask fits the wearer, they will not be able to taste the solution.

When COVID-19 struck, the increase in demand for fit-testing supplies, combined with breakdowns in manufacturing and supply chains, meant it became very difficult to get qualitative test equipment, with wait times extending weeks or even months.

“Solving the fit-testing supply crisis is critical to enable hospitals and businesses to properly protect their workers,” said O’Kelly.

Meanwhile, those outside of healthcare facilities who use non-sealing face masks are left with no reliable way to determine the fit of their masks. “Many people are using KN95 or FFP2 masks,” said O’Kelly. “While these masks can offer high levels of protection, they do not fit everyone. We also wanted to offer a way for the public, particularly those who are at high risk, to evaluate the fit of these masks for themselves.”

Previous research has assessed the safety and efficacy of homemade testing solutions; however, no effective alternatives to the atomising equipment or enclosures had yet been identified.

Now, the researchers have identified alternatives to these pieces of the testing apparatus which are around a quarter of the cost of commercial equipment and are readily available from many retailers, including Amazon.

To diffuse the solution, the researchers tested an aroma diffuser, humidifier, mist maker and spray bottle. For the enclosure, they tested a plastic bag, testing hood, a clear storage cube and no enclosure. Testers first underwent quantitative fit-testing to assess the fit on their faces before the qualitative methods. Quantitative testing measures the number of particles inside and outside the mask and is highly accurate. However, it is also time-consuming and expensive, which is why qualitative testing is more frequently used in healthcare settings.

Using an N95 mask from 3M and a KN95 mask from a Chinese manufacturer, the testers then assessed the alternative devices and enclosures. A solution of sodium saccharin – an artificial sweetener – was aerosolised for 60 seconds at a time, and testers were asked whether they could taste the sweetener or not. The test was then repeated with the tester causing an intentional gap in the fit by placing the tip of a finger between the mask and their face.

They found that the combination of an aroma diffuser and a small container, such as a large plastic bag, provided the most accurate and most sensitive setup, with results comparable to commercial qualitative fit-testing solutions.

“Our homemade replacement requires further testing for safety and efficacy: in particular, the use of a plastic bag to concentrate the vapour remains a safety concern,” said O’Kelly. “However, we were happy to find an inexpensive setup to assess the fit of masks when used in combination with homemade fit-testing solution. Given the importance of masks in slowing the spread of COVID-19 and other airborne viruses, it’s essential that they fit properly, especially in healthcare settings.”

More information is available at www.facemaskresearch.com. 

Reference:
Eugenia O’Kelly et al. ‘Performing Qualitative Mask Fit Testing Without a Commercial Kit: Fit Testing Which Can Be Performed at Home and at Work.’ Disaster Medicine and Public Health Preparedness (2020). DOI: 10.1017/dmp.2020.352

The AI technology, known as InnerEye, is the result of an eight-year collaboration between researchers at Cambridge-based Microsoft Research, Addenbrooke’s Hospital and the University of Cambridge.

InnerEye aims to save clinicians many hours of time laboriously marking up patient scans prior to radiotherapy. The team has demonstrated how machine learning (ML) models built using the InnerEye open-source technology can cut this preparation time by up to 90% - meaning that waiting times for starting potentially life-saving radiotherapy treatment can be dramatically reduced.

Health and Social Care Secretary Matt Hancock said: “New innovations like this can make all the difference to patients and I am proud to see we are once again leading the way in new cancer treatments.

“Helping people receive treatment faster is incredibly important and will not only improve recovery rates but will save clinicians precious time so they can focus on caring for patients.

“Embracing new technologies will help save lives and is vital for the sustainability of the NHS, and our NHS Long Term Plan will continue to deliver the best possible care for patients so that we can offer faster, more personalised and effective cancer treatment for all.”

Dr Raj Jena from the Department of Oncology at the University of Cambridge and an oncologist at Addenbrooke’s, who co-leads InnerEye, said: “These results are a game-changer. To be diagnosed with a tumour of any kind is an incredibly traumatic experience for patients. So as clinicians we want to start radiotherapy promptly to improve survival rates and reduce anxiety. Using machine learning tools can save time for busy clinicians and help get our patients onto treatment as quickly as possible.”

Dr Yvonne Rimmer, also from at Addenbrooke's, said: “There is no doubt that InnerEye is saving me time. It’s very good at understanding where tumours and healthy organs are. It’s speeding up the process so I can concentrate on looking at a patient’s diagnostic images and tailoring treatment to them.

“But it’s important for patients to know that the AI is helping me do my job; it’s not replacing me in the process. I double check everything the AI does and can change it if I need to. The key thing is that most of the time, I don’t need to change anything.”

Up to half of the population in the UK will be diagnosed with cancer at some point in their lives. Of those, half will be treated with radiotherapy, often in combination with other treatments such as surgery, chemotherapy, and increasingly immunotherapy.

Radiotherapy involves focusing high-intensity radiation beams to damage the DNA of hard cancerous tumours while avoiding surrounding healthy organs. This is a critical tool, with around 40% of successfully treated patients undergoing some form of radiotherapy.

Planning radiotherapy treatment can be a lengthy process. It starts with a 3D CT (Computed Tomography) imaging scan of the part of the body to be targeted. These CT images come in the form of stacks of 2D images, dozens of images deep, each of which must be examined and marked up by a radiation oncologist or specialist technician. This process is called contouring. In each image, an expert must manually draw a contour line around the tumours and key healthy organs at risk in the target area using dedicated computer software. For complex cases, this can take several hours in the planning of a single patient’s treatment.

This image segmentation task is a rate-limiting factor in the cancer treatment pathway for radiotherapy, which increases the burden of time on clinicians and the financial cost to hospitals. As this task is subjective, there can be significant variability across experts and institutions where acquisition protocols and patient demographics vary. This is a limitation to the use of imaging in clinical trials and can introduce variability in patient care.

Research published by the team in JAMA Network Open confirms that the InnerEye ML models can accurately and rapidly carry out the otherwise lengthy ‘image segmentation’ requiring hours of expert clinicians’ time.

Head of Health Intelligence at Microsoft Research, Aditya Nori, said: “This is the first time, we believe, that an NHS Trust has implemented its own deep learning solution trained on their own data, so it can be used on their patients. It paves the way for more NHS Trusts to take advantage of open-source AI tools to help reduce cancer treatment times.”

The InnerEye Deep Learning Toolkit has been made freely available as open-source software by Microsoft.

While ML models developed using the tool need to be tested and validated in each individual healthcare setting, doctors at Cambridge University Hospitals (CUH) have demonstrated how the technology can be applied in clinical settings.

Reference
Ozan Oktay, et al. Evaluation of Deep Learning to Augment Image-Guided Radiotherapy for Head and Neck and Prostate Cancers. JAMA Network Open; 30 Nov 2020; DOI: 10.1001/jamanetworkopen.2020.27426

Adapted from press releases from Microsoft and Cambridge University Hospitals NHS Foundation Trust. 

In a study published today in Science Advances, researchers from the University of Cambridge show that tiny components within the cell are the biological engines behind effective protein production.

The endoplasmic reticulum (ER) is the cell’s protein factory, producing and modifying the proteins needed to ensure healthy cell function. It is the cell’s biggest organelle and exists in a web-like structure of tubes and sheets. The ER moves rapidly and constantly changes shape, extending across the cell to wherever it is needed at any given moment.

Using super-resolution microscopy techniques, researchers from Cambridge’s Department of Chemical Engineering and Biotechnology (CEB) have discovered the driving force behind these movements – a breakthrough that could have significant impact on the study of neurodegenerative diseases.

“It has been known that the endoplasmic reticulum has a very dynamic structure – constantly stretching and extending its shape inside the cell,” said Dr Meng Lu, research associate in the Laser Analytics Group, led by Professor Clemens Kaminski.

“The ER needs to be able to reach all places efficiently and quickly to perform essential housekeeping functions within the cell, whenever and wherever the need arises. Impairment of this capability is linked to diseases including Parkinson’s, Alzheimer’s, Huntington’s and ALS. So far there has been limited understanding of how the ER achieves these rapid and fascinating changes in shape and how it responds to cellular stimuli.”

Lu and colleagues discovered that another cell component holds the key – small structures, that look like tiny droplets contained in membranes, called lysosomes.

Lysosomes can be thought of as the cell’s recycling centres: they capture damaged proteins, breaking them down into their original building blocks so that they can be reused in the production of new proteins. Lysosomes also act as sensing centres – picking up on environmental cues and communicating these to other parts of the cell, which adapt accordingly.

There can be up to 1,000 or so lysosomes zipping around the cell at any one time and with them, the ER appears to change its shape and location, in an apparently orchestrated fashion.

What surprised the Cambridge scientists was their discovery of a causal link between the movement of the tiny lysosomes within the cell and the reshaping process of the large ER network.

“We could show that it is the movement of the lysosomes themselves that forces the ER to reshape in response to cellular stimuli,” said Lu. “When the cell senses that there is a need for lysosomes and ER to travel to distal corners of the cell, the lysosomes pull the ER web along with them, like tiny locomotives.”

From a biological point of view, this makes sense: The lysosomes act as a sensor inside the cell, and the ER as a response unit; co-ordinating their synchronous function is critical to cellular health.

To discover this surprising bond between two very different organelles, Kaminski’s research team made use of new imaging technologies and machine learning algorithms, which gave them unprecedented insights into the inner workings of the cell. 

“It is fascinating that we are now able to look inside living cells and see the marvellous speed and dynamics of the cellular machinery at such detail and in real time,” said Kaminski. “Only a few years ago, watching organelles going about their business inside the cell would have been unthinkable.”

The researchers used illumination patterns projected onto living cells at high speed, and advanced computer algorithms to recover information on a scale more than one hundred times smaller than the width of a human hair. To capture such information at video rates has only recently become possible.

The researchers also used machine learning algorithms to extract the structure and movement of the ER networks and lysosomes in an automated fashion from thousands of datasets.

The team extended their research to look at neurons or nerve cells – specialised cells with long protrusions called axons along which signals are transmitted. Axons are extremely thin tubular structures and it was not known how the movement of the very large ER network is orchestrated inside these structures.

The study shows how lysosomes travel easily along the axons and drag the ER along behind them. The researchers also show how impairing this process is detrimental to the development of growing neurons.

Frequently, the researchers saw events where the lysosomes acted as repair engines for disconnected or broken pieces of ER structure, merging and fusing them into an intact network again. The work is therefore relevant for an understanding of disorders of the nervous system and its repair.

The team also studied the biological significance of this coupled movement, providing a stimulus – in this case nutrients – for the lysosomes to sense. The lysosomes were seen to move towards this signal, dragging the ER network behind so that the cell can elicit a suitable response.

“So far, little was known on the regulation of ER structure in response to metabolic signals,” said Lu. “Our research provides a link between lysosomes as sensors units that actively steer the local ER response.”

The team hopes that their insights will prove invaluable to those studying links between disease and cellular response, and their own next steps are focused on studying ER function and dysfunction in diseases such as Parkinson’s and Alzheimer’s.

Neurodegenerative disorders are associated with aggregation of damaged and misfolded proteins, so understanding the underlying mechanisms of ER function is critical to research into their treatment and prevention.  

“The discoveries of the ER and lysosomes were awarded the Nobel Prize many years ago – they are key organelles essential for healthy cellular function,” said Kaminski. “It is fascinating to think that there is still so much to learn about this system, which is incredibly important to fundamental biomedical science looking to find the cause and cures of these devastating diseases.”

Reference:
Meng Lu et al. 'The structure and global distribution ofthe endoplasmic reticulum network is actively regulated by lysosomes.' Science Advances (2020). DOI: 10.1126/sciadv.abc7209

Chronic subdural haematoma is one of the most common neurological disorders and mainly affects older people. People affected often have headaches, deteriorating memory, confusion, balance problems or limb weakness. Surgery to drain the liquid collection is effective with the majority of patients improving.

A commonly used steroid, dexamethasone, has been used alongside surgery or instead of it since the 1970s. However, consensus has been lacking regarding the use of dexamethasone, especially since no high-quality studies confirming its effectiveness had been conducted until now.

With funding from the UK National Institute Health Research, a group of doctors and researchers from 23 neurosurgical units in the United Kingdom enrolled 748 patients with chronic subdural haematoma in the “Dexamethasone in Chronic Subdural Haematoma (Dex-CSDH)” randomised trial. A total of 375 patients were randomised to receive a two-week tapering course of dexamethasone and were compared with 373 patients randomised to an identical matching placebo.

The results of the study, published today in the New England Journal of Medicine, show that patients who received dexamethasone had a lower chance of favourable recovery at six months compared to patients who received placebo. More specifically, the vast majority of patients in both groups had an operation to drain the haematoma and had experienced significant functional improvement at six months compared to their initial admission to hospital.

Fewer patients in the dexamethasone group required repeat surgery for a recurrent haematoma compared to patients in the placebo group. However, 84% of patients who received dexamethasone had recovered well at 6 months compared to 90% of patients who received placebo.

Peter Hutchinson, Professor of Neurosurgery at the University of Cambridge and the trial’s Chief Investigator, said: “Chronic subdural haematoma has been steadily increasing in frequency over the past decades. Patients affected are often frail and have other co-existing medical conditions. Since the 1970s, dexamethasone has been used as a drug alongside or instead of surgery with a few studies reporting good results.

“Our trial sought to determine if dexamethasone should be offered routinely to all patients with chronic subdural haematoma or if its use should be abandoned. Based on our findings, we believe that dexamethasone should not be used in patients with chronic subdural haematoma anymore.”

Angelos Kolias, Lecturer of Neurosurgery at the University of Cambridge and the trial’s Co-chief Investigator, added: “The results of the study were surprising given that dexamethasone seemed to help reduce the number of repeat surgeries. However, this simply reinforces the importance of conducting high-quality trials with patient-reported outcomes as the main outcomes of interest”.

Ellie Edlmann, the trial’s research fellow, currently a Clinical Lecturer at the University of Plymouth, concluded: “Credit is due to all doctors and researchers from across the NHS who worked tirelessly in order to enrol all eligible patients in the trial; in particular, the role of trainee neurosurgeons, members of the British Neurosurgical Trainee Research Collaborative, needs to be highlighted. We sincerely thank all patients and their carers, as without their altruistic participation, this trial would not have been possible.”

The trial was funded by the National Institute for Health Research (NIHR), with further support from the NIHR Cambridge Biomedical Research Centre, the NIHR Brain Injury MedTech Co-operative, the Royal College of Surgeons of England, and the Rosetrees Trust.

Reference
Hutchinson, PJ et al. Trial of Dexamethasone for Chronic Subdural Hematoma. NEJM; 16 Dec 2020; DOI: 10.1056/NEJMoa2020473

The University of Cambridge has launched the Regulatory Genome Project, a transformational initiative to sequence the world’s vast amount of regulatory text to create a comprehensive open repository of machine-readable regulatory information for use by regulatory agencies and businesses around the world.

This multi-year project – which includes an expanding collaboration network of regulatory agencies, companies, and academic researchers – has been inspired by the scientific and commercial innovation that followed the collective effort to code the human genome.

The project aims to provide an open-source infrastructure for all countries, particularly in developing regions, to have the same digital capabilities as advanced economies to identify regulatory obligations around the world. This is particularly important as consumers have increasingly adopted digital financial services, which has opened up new areas of risk that require regulation.

Drawing on research from the Cambridge Centre for Alternative Finance (CCAF) at Cambridge Judge Business School and the Department of Computer Science and Technology, the project uses machine learning and natural language processing to ‘sequence’ huge amounts of regulatory text, starting with financial regulation. This offers regulators and firms the opportunity to acquire unprecedented capabilities in the development, processing and analysis of regulation.

“The Regulatory Genome Project combines the University’s research with its convening influence to deliver societal and economic impact with the potential to be global, transformational and enduring,” said Professor Eilís Ferran, Pro-Vice-Chancellor for Institutional and International Relations at the University of Cambridge.

As part of the project’s structure, a new University-affiliated company called Regulatory Genome Development Ltd has been formed to provide support to third parties building applications using the code and data in the Regulatory Genome.

The Regulatory Genome originated out of a research project led by the CCAF with initial funding provided by the Omidyar Network to create a solution – named RegSimple – that simplifies the comparison of regulations across different jurisdictions. Additional funding has been provided by the UK’s Foreign, Commonwealth & Development Office to expand the scope and functionality of RegSimple to serve the needs of regulators in developing and emerging economies. Regulators from more than 20 jurisdictions are already contributing to the project.

“We are excited about the vast potential of this project to benefit both public and private sector interests,” said Dr Robert Wardrop, Director of the Cambridge Centre for Alternative Finance. “An open access repository of regulatory information will serve to level the regulatory playing field for those who develop and comply with regulation, particularly in emerging markets, and serve as a key resource for researchers in deepening their understanding how the regulatory landscape for digital financial services is evolving.”

Originally published on the Cambridge Judge Business School website.

In early March, the World Health Organization declared COVID-19 a pandemic and many countries put in place drastic safety measures to control the spread of the virus, including an extended lockdown period.

In the UK, the first nationwide lockdown started on 23 March and lasted until 1 June, when restrictions began to be eased. Since then more localised lockdowns have been implemented where necessary.

A team of researchers at the University of Cambridge has explored whether the stress of the pandemic and lockdown measures affected people’s alcohol consumption. Between 14 and 28 May 2020, 1,346 people around the world completed an online survey about their drinking habits before and during lockdown. The researchers used their responses to compare the amount of alcohol consumed during lockdown against that in November 2019, as well as their drinking severity (occurrences of problem drinking such as drinking to the point of memory loss or neglecting personal responsibilities due to drinking). They also assessed mental health factors such as depression and anxiety.

The survey revealed that while the units of alcohol consumed per week decreased during lockdown – down from a mean average of 8.32 units in November to 8.03 during lockdown – a substantial percentage of individuals (36%) increased their drinking during lockdown. In the UK, the units of alcohol consumed per week increased from 10.94 to 11.25 units.

Samantha N. Sallie, the study’s first author and a PhD student at the Department of Psychiatry, said: “While in countries such as Canada and the USA people drank less during lockdown, in the UK there was a small increase in alcohol consumption.”

Older individuals tended to increase their alcohol consumption more than younger people during lockdown, from 10 to 11 units weekly. Age may play a particularly unique role in the context of COVID-19 due to the greater need for older people to have more stringent isolation, with potentially fewer support mechanisms, and hence a risk of greater isolation and loneliness, as well as concern about the impact of COVID-19 on their personal health.

Respondents with children reported a greater increase in alcohol consumption during lockdown, of between 0.54 and 2.02 units, though their depression and anxiety scores were lower than for those without children. The researchers say this suggests the additional burden of childcare and home schooling contributed to the tendency towards drinking, possibly in the context of stress relief, but the presence of children may also be protective against depression and anxiety.

“For parents having to take on extra childcare responsibilities during lockdown, possibly at the same time as having to manage changes to their work routine, it’s possible that the extra stress increased their tendency to drink,” said Sallie. “On the other hand, having children may mitigate against loneliness that has been highlighted as a major issue during the isolation of lockdown.”

The team found that essential workers – specifically healthcare workers responsible for taking care of individuals with COVID-19 – showed an increase in drinking amount of between 0.45 and 1.26 units, while those whose loved ones became severely ill or died from COVID-19 showed an increase in problem drinking during the lockdown.

“This demonstrates how the virus itself has affected alcohol consumption in those who have had close contact with the very real and devastating effects of COVID-19,” added Sallie.

Although men consumed more alcohol than women, they showed a decrease in both drinking amount and severity during lockdown, while women demonstrated the opposite trend, with women consuming an extra unit of alcohol a week during lockdown. This finding corroborates evidence that indicates women are more likely than men to consume alcohol in order to cope with stress.

Individuals who reported a change in their employment status or were isolating alone were more likely to have higher depression scores, but showed no change in their drinking behaviour. Those individuals isolating with others but reporting a poor relationship were more likely to have higher depression and anxiety scores.

Dr Valerie Voon, senior author of the study from the University of Cambridge, said: “As COVID-19 remains part of daily life, many of us are turning to alcohol to cope with stress. For many people, drinking in moderation can be help with stress relief, but for others it can be more problematic.

“Alcohol misuse is a major public health issue in the United Kingdom, costing £21-52 billion with NHS costs of £3.5 billion per year.  Our findings highlight a need to identify those individuals who are at risk for problem drinking so we can offer them greater support during the ongoing pandemic.”

The researchers say there may be a number of reasons for the overall decrease in alcohol use and problematic use, including stringent lockdown measures leading to a decrease in the availability of alcoholic drinks within the immediate household and because people tend to consume alcohol in social situations, such as at the pub or when eating out.

Reference
Sallie, S.N. et al. Assessing International Alcohol Consumption Patterns During Isolation from the COVID-19 Pandemic Using an Online Survey: Highlighting Negative Emotionality Mechanisms. BMJ Open; 26 Nov 2020; DOI: 10.1136/bmjopen-2020-044276

The findings, published in PNAS, suggest Earth’s natural mechanism for removing carbon dioxide (CO₂) from the atmosphere via the weathering of rocks may in fact be weaker than scientists had thought – calling into question the exact role of rocks in alleviating warming over millions of years.

The research also suggests there may be a previously unknown sink drawing CO₂ from the atmosphere and impacting climate changes over long timescales, which researchers now hope to find.

Weathering is the process by which atmospheric carbon dioxide breaks down rocks and then gets trapped in sediment. It is a major part of our planet’s carbon cycle, shuttling carbon dioxide between the land, sea and air, and influencing global temperatures.

“Weathering is like a planetary thermostat - it’s the reason why Earth is habitable. Scientists have long suggested this is why we don’t have a runaway greenhouse effect like on Venus,” said lead author Ed Tipper from Cambridge’s Department of Earth Sciences. By locking carbon dioxide away in sediments, weathering removes it from the atmosphere over long timescales, reducing the greenhouse effect and lowering global temperatures.

The team’s new calculations show that, across the globe, weathering fluxes have been overestimated by up to 28%, with the greatest impact on rivers in mountainous regions where rocks are broken down faster.

They also report that three of the largest river systems on Earth, including the neighbouring Yellow and Salween Rivers with their origins on the Tibetan Plateau and the Yukon River of North America, do not absorb carbon dioxide over long timescales - as had been thought.

For decades, the Tibetan plateau has been invoked as a long-term sink for carbon and mediator of climate. Some 25% of the sediment in the world’s oceans originate from the plateau.

“One of the best places to study the carbon cycle are rivers, they are the arteries of the continents. Rivers are the link between the solid Earth and oceans – hauling sediments weathered from the land down to the oceans where their carbon is locked up in rocks,” said Tipper.

“Scientists have been measuring the chemistry of river waters to estimate weathering rates for decades,” said co-author Victoria Alcock “Dissolved sodium is one of the most commonly measured products  of weathering  – but we’ve shown that it’s not that simple, and in fact sodium often comes from elsewhere.”

Sodium is released when silicate minerals, the basic building blocks of most of Earth’s rocks, dissolve in carbonic acid - a mix of carbon dioxide in the atmosphere and rainwater.

However, the team found not all sodium comes from this weathering process. “We’ve found an additional source of sodium in river waters across the globe,” said co-author Emily Stevenson. “That extra sodium is not from weathered silicate rocks as other studies assume, but in fact from very old clays which are being eroded in river catchments.”

Tipper and his research group studied eight of the largest river systems on Earth, a mission involving 16 field seasons and thousands of lab analyses in search of where that extra sodium was coming from.  

They found the answer in a soupy ‘gel’ of clay and water – known as the cation exchange pool – which is carried along by muddy river sediment.

The exchange pool is a reactive hive of cations – positively charged ions like sodium - which are weakly bonded to clay particles. The cations can easily swap out of the gel for other elements like calcium in river water, a process that can take just a few hours.

Although it has been described in soils since the 1950s, the role the exchange pool plays in supplying sodium to rivers has been largely neglected.

“The chemical and isotopic makeup of the clays in the exchange pool tell us what they are made of and where they’ve come from,” said co-author Alasdair Knight. “We know that many of the clays carried by these rivers come from ancient sediments, and we suggest that some of the sodium in the river must come from these clays.”

The clays were originally formed from continental erosion millions of years ago. On their journey downstream they harvested cations from the surrounding water –  their exchange pool picking up sodium on reaching the sea. Today, after being uplifted from the seafloor, these ancient clays – together with their sodium - are now being eroded by modern rivers.

This old sodium, which can switch out of the clays in the exchange pool and into river water, has previously been mistaken as the dissolved remnants of modern weathering.

“Generating just one data point took a huge amount of work in the lab and we also had to do a lot of maths,” said Stevenson. “It’s like unmixing a cake, using a forensic approach to isolate key ingredients in the sediments, leaving behind the exchange pool and the clays. People have used the same methods for a really long time - and they work - but we’ve been able to find an extra ingredient that provides the sodium and we need to account for this.”

“It's thanks to the hard work of many collaborators and students over many years that our samples had the scope to get to grips with this complex chemical process at a global scale,” said Tipper.

Scientists are now left to puzzle over what else could be absorbing Earth’s carbon dioxide over geological time. There are no certain candidates – but one controversial possibility is that life is removing carbon from the atmosphere. Another theory is that silicate dissolution on the ocean floor or volcanic arcs may be important. “People have spent decades looking on the continents for weathering - so maybe we now need to start expanding where we look,” said Tipper.

Reference:
Edward T. Tipper et al. ‘Global silicate weathering flux overestimated because of sediment–water cation exchange.’ PNAS (2020). DOI: 10.1073/pnas.2016430118

The facility was set up in a collaboration between the University of Cambridge and two major pharmaceutical partners, AstraZeneca and GSK. Soon after its launch, the facility was brought into the Government’s national diagnostic lab network, the largest in British history.

The University has been able to share its world-leading research expertise with the innovation and robotics know-how from its two pharmaceutical partners to create a new, high-throughput centre. The facility is based at the Anne McLaren Building on the Cambridge Biomedical Campus.

Hundreds of volunteers were recruited and trained from across the three organisations to get the Centre up and running, including researchers from the University. Each volunteer stepped forward at a time of national crisis with their own reasons for wanting to contribute to the COVID-19 testing programme.

Innovative robotics and automation were installed and an entire supply chain was sourced and implemented to ensure the testing facility was both resilient and highly effective. All of this was done in just five weeks, an operation which would usually take six months.

Since it began operating, the facility has processed more than 2 million tests.

“This is a tremendous achievement and testament to the hard work of the team involved in setting up and running this facility,” said Professor Andy Neely, Pro-Vice-Chancellor for Enterprise and Business Relations at the University of Cambridge. “I would like to thank everyone who has played a part in making the Centre a huge success and enabling it to play an important role in helping keep Cambridgeshire and the UK safe.”

Over the past three years, working groups across the collegiate University have been assessing the impact of leaving the European Union with or without a deal. They have been making sure that the University and the Colleges are as well placed as they can be to deal with the consequences of any scenario. 

In the weeks ahead, we will communicate directly to staff and students on issues including travel, personal data and research funding, as and when necessary. Staff and students can find the very latest information from the University on our Brexit webpages, which I ask you to consult regularly for any updates.  

Cambridge colleagues will continue to engage with the government and policy-makers to seek clarity on issues where uncertainty remains. 

Looking ahead 

Today’s outcome is only the latest step in a long and complex process. While we now know the contours of the agreement, is impossible to predict exactly what the short, medium and long-term implications of this form of Brexit will be. 

I am in no doubt that Cambridge will be able to adapt successfully to the new realities. Even as it does, I am determined that we look forward and continue to build on the decades of openness, collaboration and cross-border academic inquiry that have allowed us – working alongside our European partners – to create knowledge and tackle global challenges.  

The collegiate University’s leadership is determined that the UK’s departure from the European Union will not deter us from remaining an open and welcoming University, or erase long-standing bonds of collaboration and friendship.  

It is now up to institutions like ours to help shape our future relationship with our European and global partners. We have every intention of doing so. 

We will continue to work alongside our valued European partners. We will continue to build collaborations with organisations and Universities across the continent that share our aspirations and values. And we will continue to reach out to friends around the world – from Munich to Nanjing, from Paris to Delhi – to show through our actions that we are a global university.  

Professor Stephen J Toope 

Vice-Chancellor, University of Cambridge

Professor Simon Baron-Cohen, Director of Cambridge’s Autism Research Centre and a Fellow of Trinity College, has been knighted for services to people with autism research and autistic people. He is one of the top autism researchers in the world, and is a Fellow of the British Academy, the Academy of Medical Sciences, and the British Psychological Society. He served as Chair of the NICE Guidelines for autism and is Director of the charity the Autism Centre of Excellence and Vice President of the National Autistic Society. He was President of the International Society for Autism Research. He created the first clinic worldwide to diagnose autism in adults and championed the human rights of autistic people at the UN. He is author of The Essential Difference, Zero Degrees of Empathy, and The Pattern Seekers, which have captured the public imagination.

Professor Baron-Cohen said: “This honour came as a complete surprise, and I accept it on behalf of the talented team of scientists at the Autism Research Centre in Cambridge, and on behalf of the Autism Research Trust, the charity that has supported us. The basic needs and human rights of autistic people and their families are still not being met by statutory services, due to insufficient funding, so we are creating a new charity, the Autism Centre of Excellence, to address this gap.”

Professor Usha Goswami, Director for the Centre for Neuroscience in Education, Professor of Cognitive Developmental Neuroscience and Fellow of St. John’s College, becomes CBE for services to educational research.

Her research focuses on children’s cognitive development, particularly the development of language and literacy. Her world-leading work on dyslexia led to the discovery that children with the disorder hear language differently, showing it to be a language disorder and not a visual disorder as previously thought. This significant finding is enabling the development of transformative new educational interventions, which will benefit millions of children with dyslexia worldwide.

“I am deeply honoured to receive this award,” said Professor Goswami. “I have been interested in children’s development since training as a primary school teacher and it is wonderful to have my research recognised in this way.

Professor Val Gibson, Professor of High Energy Physics at the Cavendish Laboratory, University Gender Equality Champion and Fellow of Trinity College, has been made OBE for service to Science, Women in Science and Public Engagement.

Her research interest is the search for new phenomena using particles containing heavy quarks, which are produced in copious amounts at the Large Hadron Collider, and hold the key to our understanding of the matter-antimatter imbalance in the Universe. From 2004-2008, she was the UK Spokesperson and PI for the LHCb experiment and had ultimate responsibility to deliver the UK contributions to the experiment. She is currently the Chair of the LHCb Collaboration Board, the decision-making body for the experiment, with representatives from 78 institutes across the world.

Professor Gibson said: “It is an honour to be recognised for all three of my passions: research into the most fundamental particles and forces of nature, including the mystery of why we live in a Universe made of matter and not antimatter; support for gender equality and diversity in science; and the public engagement activities I have undertaken over many years.”

Dr Michael Weekes from the Cambridge Institute for Therapeutic Immunology and Infectious Disease (CITIID) has been awarded the British Empire Medal for or services to the NHS during COVID-19. He developed a comprehensive COVID-19 screening programme for Cambridge University Hospitals healthcare workers, Cambridge University staff and students.

Dr Weekes said: "I’m deeply honoured to have had the chance to be part of the team that set up COVID testing for Cambridge University Hospitals. I’d particularly like to acknowledge the contribution of Steve Baker, Rob Howes and Giles Wright, who played vital roles in testing and organisation. I hope that vaccination will soon mean that hospitals become even safer places to work and be cared for."

Like many clinical researchers, my latest work has focused on urgent public health studies in response to the pandemic. Normally I have three roles: as a Consultant Psychiatrist and Deputy Medical Director at Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), Clinical Director of CPFT’s Windsor Research Unit in Fulbourn, and Dementia Lead for the National Institute for Health Research (NIHR) Clinical Research Network Eastern. Most of my research until recently has been in dementia, and in particular trialling potential treatments with the Gnodde Goldman Sachs Translational Neuroscience Unit. I still do that, but 2020 has also thrown me into the world of viral pandemics in a completely unexpected way. 

The Windsor Research Unit team and I are supporting delivery of coronavirus vaccine trials in Cambridge, including the Oxford (ChAdOx) vaccine. The way that CPFT, the University, Cambridge University Hospitals NHS Foundation Trust (CUH) and Royal Papworth Hospital NHS Foundation Trust (RPH) pulled together to rapidly deliver a vaccine trial was extraordinary to see, and an honour to be part of. It’s a milestone partnership for research in this region, and we are lucky to have the support and infrastructure of the NIHR across the UK.

We couldn’t have hoped for a better result in terms of overall vaccine efficacy, and I'm delighted to hear the vaccine has now been approved for use. The fact we had such a clear and important goal really galvanised us and there was a great spirit in the team. There are too many people to name for their outstanding efforts, and this research would not have been possible without the entire team behind it, and all the health and care workers across Cambridgeshire and Peterborough who volunteered. I cannot thank everyone involved enough! I hope I have made new friendships that endure, and I have such great respect for many of the people involved.

The next challenge is delivering effective vaccines to a global population as quickly as possible. The creation and testing of COVID-19 vaccines within a year has been one of the greatest scientific and medical achievements of our time, made possible through new partnerships, with researchers all over the world working together and sharing data. We need to get effective vaccines out to people as soon as they are approved, starting with the most vulnerable and at risk.

The pandemic has posed crucial questions for our clinical services. My team also collaborated to publish papers addressing some of these including: the role of community services in dealing with COVID-19, the impact of the virus on community and mental health services and the risk factors for mortality, the provision of memory assessments during the pandemic, and mathematical modelling of rates of spread in community healthcare settings.

We must now question whether we have got the balance of governance and delivery right on clinical trials. We have demonstrated that we can safely and accurately deliver trials in a year - this previously might have taken ten years, largely due to governance processes. How can we capture what we have learned, to deliver clinical trials just as safely in a much shorter timeframe in future?
 
We have learned so much from this experience, and our research team are now determined to transfer knowledge and skills for testing vaccines into developing new effective treatments for dementia, which is still the leading cause of death in the UK.
 
When the pandemic is over I just want to lie down with a wet towel over my face! Professionally, I’m looking forward to finding better treatments for dementia. Personally I love playing music in my spare time but haven’t been able to play with others since the pandemic began, so I can’t wait to be back in a band rehearsal room.
 
Ben Underwood is a Visiting Researcher in the University of Cambridge’s Department of Psychiatry, where he will become University Lecturer in Older People’s Health from April 2021.

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