Mindfulness is typically defined as ‘the awareness that emerges through paying attention on purpose, in the present moment, and nonjudgmentally to the unfolding of experience moment by moment’. It has become increasingly popular in recent years as a way of increasing wellbeing and reducing stress levels.

In the UK, the National Health Service offers therapies based on mindfulness to help treat mental health issues such as depression and suicidal thoughts. However, the majority of people who practice mindfulness learn their skills in community settings such as universities, workplaces, or private courses. Mindfulness-based programmes are frequently promoted as the go-to universal tool to reduce stress and increase wellbeing, accessible to anyone, anywhere.

Many randomised controlled trials (RCTs) have been conducted around the world to assess whether in-person mindfulness training can improve mental health and wellbeing, but the results are often varied. In a report published today in PLOS Medicine, a team of researchers from the Department of Psychiatry at the University of Cambridge led a systematic review and meta-analysis to examine the published data from the RCTs. This approach allows them to bring together existing – and often contradictory or under-powered – studies to provide more robust conclusions.

The team identified 136 RCTs on mindfulness training for mental health promotion in community settings. These trials included 11,605 participants aged 18 to 73 years from 29 countries, more than three-quarters (77%) of whom were women.

The researchers found that in most community settings, compared with doing nothing, mindfulness reduces anxiety, depression and stress, and increases wellbeing. However, the data suggested that in more than one in 20 trials settings, mindfulness-based programmes may not improve anxiety and depression.

Dr Julieta Galante from the Department of Psychiatry at the University of Cambridge, the report’s first author, said: “For the average person and setting, practising mindfulness appears to be better than doing nothing for improving our mental health, particularly when it comes to depression, anxiety and psychological distress – but we shouldn’t assume that it works for everyone, everywhere.

“Mindfulness training in the community needs to be implemented with care. Community mindfulness courses should be just one option among others, and the range of effects should be researched as courses are implemented in new settings. The courses that work best may be those aimed at people who are most stressed or in stressful situations, for example health workers, as they appear to see the biggest benefit.”

The researchers caution that RCTs in this field tended to be of poor quality, so the combined results may not represent the true effects. For example, many participants stopped attending mindfulness courses and were not asked why, so they are not represented in the results. When the researchers repeated the analyses including only the higher quality studies, mindfulness only showed effects on stress, not on wellbeing, depression or anxiety.

When compared against other ‘feel good’ practices such as exercise, mindfulness fared neither better nor worse. Professor Peter Jones, also from Cambridge’s Department of Psychiatry, and senior author, said: “While mindfulness is often better than taking no action, we found that there may be other effective ways of improving our mental health and wellbeing, such as exercise. In many cases, these may prove to be more suitable alternatives if they are more effective, culturally more acceptable or are more feasible or cost effective to implement. The good news is that there are now more options.”

The researchers say that the variability in the success of different mindfulness-based programmes identified among the RCTs may be down to a number of reasons, including how, where and by whom they are implemented as well as at whom they are targeted. The techniques and frameworks taught in mindfulness have rich and diverse backgrounds, from early Buddhist psychology and meditation through to cognitive neuroscience and participatory medicine – the interplay between all of these different factors can be expected to influence how effective a programme is.

The number of online mindfulness courses has increased rapidly, accelerated further by the COVID-19 pandemic. Although this review has not looked at online courses, studies suggest that these may be as effective as their offline counterparts, despite most lacking interactions with teacher and peers.

Dr Galante added: “If the effects of online mindfulness courses vary as widely according to the setting as their offline counterparts, then the lack of human support they offer could cause potential problems. We need more research before we can be confident about their effectiveness and safety.”

The research was funded by the National Institute for Health Research (NIHR) Applied Research Collaboration East of England and NIHR Cambridge Biomedical Research Centre, with additional support from the Cambridgeshire & Peterborough NHS Foundation Trust, Medical Research Council, Wellcome and the Spanish Ministry of Education, Culture and Sport.

Reference
Galante, J et al. Mindfulness-based programmes for mental health promotion in adults in non-clinical settings: A systematic review and meta-analysis of randomised controlled trials. PLOS Medicine; 11 Jan 2021; DOI: 10.1371/journal.pmed.1003481

Now, the team running the programme has joined up with researchers at the COVID-19 Genomics UK Consortium (COG-UK) to track how infections spread among the student population. They have shown how a small number of transmission events early on were likely responsible for most of the infections at the University and found little evidence of substantial transmission of SARS-CoV-2 between students and the local Cambridge community in the first five weeks of term.

Around 12,000 students living in College accommodation (80% of eligible students) signed up to the asymptomatic screening programme, which uses a pooled sample approach to reduce the number of tests to fewer than 2,000 per week. In the first weeks of term, 1-2 students from each ‘household’ were tested each week; this has now increased to all participating students being tested each week. In addition, the University offers tests to students and staff who show symptoms of potential COVID-19.

The University is also playing a leading role in COG-UK, which is sequencing the genetic code of samples of the virus isolated from infected individuals to help better understand the spread of infection. As a virus spreads, its genetic code acquires mutations. By comparing the genetic code of samples, it is possible to plot a genetic ‘family tree’ known as phylogenetic tree and to say, coupled with epidemiological information, whether two cases are related – identical or almost-identical samples are likely to be closely related, while genomes with a larger number of genetic differences are less likely to be related.

As part of this work, COG-UK is analysing virus samples from students identified as positive through the University of Cambridge’s testing programmes and comparing them to samples taken from people in the wider Cambridge community. COG-UK and the University have released their interim report, covering the first five weeks of term.

The analysis showed that in week two, 90% of infections were confined to three lineages (related viral genomes). This lack of diversity suggests that a small number of transmission events at the start of term led to the majority of infections in the University.

Outbreaks that have largely been restricted to single Colleges appear to have been contained, suggesting that measures to prevent spread of the virus were successful. In one of the largest clusters (which included 32 cases by week three), half of the students were asymptomatic, highlighting the importance of screening programmes in helping identify infected individuals.

The largest cluster of cases (139 cases by week five, including 135 students, 1 staff member and 3 individuals from the local community) was the source of ongoing transmission within the University. It included students from a number of Colleges, courses and years of study. However, it is not clear whether these can be traced back to a single event that led to dispersion amongst colleges and courses.

Dr Dinesh Aggarwal from the Department of Medicine at the University of Cambridge and a member of COG-UK said: “It appears that a few instances of the virus being introduced to the University account for the majority of cases of established transmission. This suggests to us that in most cases, when a virus was introduced, students behaving responsibly and complying with infection control measures helped stop the virus in its tracks.

“We hope it will be particularly reassuring that so far we have not found evidence of substantial transmission between our students and the local community.”

Dr Ben Warne, a Clinical Research Fellow and one of the leads on the University’s asymptomatic screening programme, added: “It’s clear we need to better understand how the virus spreads between students on different courses and at different Colleges. Once established, these widely-distributed outbreaks are more challenging to control, potentially resulting in continued spread. Genomics should help us piece together this puzzle and help us target prevention strategies.”

The team say their findings appear to suggest that a regular screening programme to detect asymptomatic infection and robust containment measures can be effective at limiting transmission both within the University and to the wider community. This will be particularly important with the emergence of a new, more transmissible variant and substantially higher levels of transmission within the community.

Patrick Maxwell, Regius Professor of Physic at the University of Cambridge, said: “Getting our screening programme up and running in time for the start of term was no small order, but we believe it has paid off. Asymptomatic screening can help identify cases of infection early, including where students are unaware of infection, and inform infection control measures. This has never been more urgent, with the emergence of the new variant.”

The University recently announced that while it will remain open, almost all teaching and learning for undergraduate and postgraduate taught students will move online for the entirety of the Lent term. Undergraduate and postgraduate taught students have been asked to remain where they are currently staying, other than for certain exceptions.

The genetic adaptions identified were similar to those made by SARS-CoV – which caused the 2002-2003 SARS epidemic – when it adapted from bats to infect humans. This suggests that there may be a common mechanism by which this family of viruses mutates in order to jump from animals to humans. This understanding can be used in future research to identify viruses circulating in animals that could adapt to infect humans (known as zoonoses) and which potentially pose a pandemic threat.

“This study used a non-infectious, safe platform to probe how spike protein changes affect virus entry into the cells of different wild, livestock and companion animals, something we will need to continue monitoring closely as additional SARS-CoV-2 variants arise in the coming months,” said Dr Stephen Graham in the University of Cambridge’s Department of Pathology, who was involved in the study.

In the 2002-2003 SARS epidemic, scientists were able to identify closely related isolates in both bats and civets – in which the virus is thought to have adapted to infect humans. However, in the current COVID-19 outbreak scientists do not yet know the identity of the intermediate host or have similar samples to analyse. But they do have the sequence of a related bat coronavirus called RaTG13 which shares 96 percent similarity to the SARS-CoV-2 genome. The new study compared the spike proteins of both viruses and identified several important differences.

SARS-CoV-2 and other coronaviruses use their spike proteins to gain entry to cells by binding to their surface receptors, for example ACE2. Like a lock and key, the spike protein must be the right shape to fit the cell’s receptors, but each animal’s receptors have a slightly different shape, which means the spike protein binds to some better than others.

To examine whether these differences between SARS-CoV-2 and RaTG13 were involved in the adaptation of SARS-CoV-2 to humans, scientists swapped these regions and examined how well these resulting spike proteins bound human ACE2 receptors – using a method that does not involve using live virus.

The results, published in the journal PLOS Biology, showed SARS-CoV-2 spikes containing RaTG13 regions were unable to bind to human ACE2 receptors effectively, while the RaTG13 spikes containing SARS-CoV-2 regions could bind more efficiently to human receptors – although not to the same level as the unedited SARS-CoV-2 spike protein. This potentially indicates that similar changes in the SARS-CoV-2 spike protein occurred historically, which may have played a key role in allowing the virus to jump the species barrier.

Researchers also investigated whether the SARS-CoV-2 spike protein could bind to the ACE2 receptors from 22 different animals to ascertain which of these, if any, may be susceptible to infection. They demonstrated that bat and bird receptors made the weakest interactions with SARS-CoV-2. The lack of binding to bat receptors adds weight to the evidence that SARS-CoV-2 likely adapted its spike protein when it jumped from bats into people, possibly via an intermediate host.

Dog, cat, and cattle ACE2 receptors were identified as the strongest interactors with the SARS-CoV-2 spike protein. Efficient entry into cells could mean that infection may be more easily established in these animals, although receptor binding is only the first step in viral transmission between different animal species.

“As we saw with the outbreaks in Danish mink farms last year, it’s essential to understand which animals can be infected by SARS-CoV-2 and how mutations in the viral spike protein change its ability to infect different species,” said Graham.

An animal’s susceptibility to infection and its subsequent ability to infect others is reliant on a range of factors – including whether SARS-CoV-2 is able to replicate once inside cells, and the animal’s ability to fight off the virus. Further studies are needed to understand whether livestock and companion animals could be receptive to COVID-19 infection from humans and act as reservoirs for this disease.

This research was funded by the Medical Research Council, the Biotechnology and Biological Sciences Research Council and Innovate UK – all part of UK Research and Innovation; the Royal Society and Wellcome.

Reference
Conceicao, C. et.al: ‘The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins’. PLOS Biology, Dec 2020. DOI:10.1371/journal.pbio.3001016

Adapted from a press release by the Pirbright Institute

The research published in European Radiology shows that combining computed tomography (CT) scans with ultrasound images creates a visual guide for doctors to ensure they sample the full complexity of a tumour with fewer targeted biopsies.

Capturing the patchwork of different types of cancer cell within a tumour – known as tumour heterogeneity – is critical for selecting the best treatment because genetically-different cells may respond differently to treatment.

Most cancer patients undergo one or several biopsies to confirm diagnosis and plan their treatment. But because this is an invasive clinical procedure, there is an urgent need to reduce the number of biopsies taken and to make sure biopsies accurately sample the genetically-different cells in the tumour, particularly for ovarian cancer patients.

High grade serous ovarian (HGSO) cancer, the most common type of ovarian cancer, is referred to as a ‘silent killer’ because early symptoms can be difficult to pick up. By the time the cancer is diagnosed, it is often at an advanced stage, and survival rates have not changed much over the last 20 years.

But late diagnosis isn’t the only problem. HGSO tumours tend to have a high level of tumour heterogeneity and patients with more genetically-different patches of cancer cells tend to have a poorer response to treatment.

Professor Evis Sala from the Department of Radiology, co-lead CRUK Cambridge Centre Advanced Cancer Imaging Programme, leads a multi-disciplinary team of radiologists, physicists, oncologists and computational scientists using innovative computing techniques to reveal tumour heterogeneity from standard medical images. This new study, led by Professor Sala, involved a small group of patients with advanced ovarian cancer who were due to have ultrasound-guided biopsies prior to starting chemotherapy.

For the study, the patients first had a standard-of-care CT scan. A CT scanner uses x-rays and computing to create a 3D image of the tumour from multiple image ‘slices’ through the body.

The researchers then used a process called radiomics – using high-powered computing methods to analyse and extract additional information from the data-rich images created by the CT scanner – to identify and map distinct areas and features of the tumour. The tumour map was then superimposed on the ultrasound image of the tumour and the combined image used to guide the biopsy procedure.

By taking targeted biopsies using this method, the research team reported that the diversity of cancer cells within the tumour was successfully captured.

Co-first author Dr Lucian Beer, from the Department of Radiology and CRUK Cambridge Centre Ovarian Cancer Programme, said of the results: “Our study is a step forward to non-invasively unravel tumour heterogeneity by using standard-of-care CT-based radiomic tumour habitats for ultrasound-guided targeted biopsies.”

Co-first author Paula Martin-Gonzalez, from the Cancer Research UK Cambridge Institute and CRUK Cambridge Centre Ovarian Cancer Programme, added: “We will now be applying this method in a larger clinical study.”

Professor Sala said: “This study provides an important milestone towards precision tissue sampling. We are truly pushing the boundaries in translating cutting edge research to routine clinical care.”

Fiona Barve (56) is a science teacher who lives near Cambridge. She was diagnosed with ovarian cancer in 2017 after visiting her doctor with abdominal pain. She was diagnosed with stage 4 ovarian cancer and immediately underwent surgery and a course of chemotherapy. Since March 2019 she has been cancer free and is now back to teaching three days a week.

“I was diagnosed at a late stage and I was fortunate my surgery, which I received within four weeks of being diagnosed, and chemotherapy worked for me. I feel lucky to be around,” said Barve.

“When you are first undergoing the diagnosis of cancer, you feel as if you are on a conveyor belt, every part of the journey being extremely stressful. This new enhanced technique will reduce the need for several procedures and allow patients more time to adjust to their circumstances. It will enable more accurate diagnosis with less invasion of the body and mind. This can only be seen as positive progress.”

This feasibility study, involving researchers from the Department of Radiology, CRUK Cambridge Institute, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, and collaborators at Cannon, was facilitated through the CRUK Cambridge Centre Integrated Cancer Medicine programme.

The goal of Integrated Cancer Medicine is to revolutionise cancer treatment using complex data integration. Combining and integrating patient data from multiple sources – blood tests, biopsies, medical imaging, and genetic tests – can inform and predict the best treatment decisions for each individual patient.

The study was funded by Cancer Research UK and The Mark Foundation for Cancer Research.

Reference
Lucian Beer, Paula Martin-Gonzalez et al. Ultrasound-guided targeted biopsies of distinct CT based radiomic tumour habitats: proof of concept. European Radiology; 14 Dec 2020; DOI: 10.1007/s00330-020-07560-8