The latest list of publications from the NIHR Cambridge Biomedical Research Centre with a brief summary.
If you are publishing research which has had funding and / or support from the NIHR Cambridge Biomedical Research Centre, please complete this form.
Publication: Brain, Behavior, and Immunity
Emanuele F.Osimo, Benjamin I.Perry, Rudolf N.Cardinal, Mary-EllenLynall, Jonathan Lewis, Arti Kudchadkar, Graham K.Murray, Jesus Perez, Peter B. Jones, Golam M.Khandaker
09 October 2020
A study with early intervention mental health service found that sixty percent of people cared for in their first episode of psychosis recovered well.
The research team used a research database to review blood markers and health outcomes for service users, in a longitudinal study of anonymous patient records between January 2013 and November 2019.
Researchers found that around sixty percent of people with first episode psychosis recovered well enough to be discharged to their GP. Several blood markers were consistently higher or lower in other people who required long term specialist psychiatric care. Read the full press story.View publication
Publication: Annals of Neurology
Maura Malpetti, Luca Passamonti, Timothy Rittman, P. Simon Jones, Patricia Vázquez Rodríguez, W. Richard Bevan‐Jones, Young T. Hong, Tim D. Fryer, Franklin I. Aigbirhio, John T. O’Brien, James B. Rowe
20 September 2020
Progressive Supranuclear Palsy (PSP) is associated with tau-protein aggregation and neuroinflammation. In this study the research team mapped these features in the brain of living patients with a brain-scanning technique called positron emission tomography (PET). They examined the relationship between tau pathology and inflammation, and their association with clinical severity.
Tau pathology and neuroinflammation occur in the same parts of the brain of patients with PSP, and they are both linked to the severity of symptoms.
Following this study the research team suggests that the combination of tau- and immune-oriented strategies may be useful for effective disease-modifying treatments in PSP.View publication
Rafa Romero-Garcia, Roxanne W. Hook, Jeggan Tiego, Richard A. I. Bethlehem, Ian M. Goodyer, Peter B. Jones, Ray Dolan, Jon E. Grant, Edward T. Bullmore, Murat Yücel & Samuel R. Chamberlain
12 September 2020
Impulsivity refers to behaviours that are inappropriate, risky, unduly hasty, and that lead to untoward outcomes. By contrast, compulsivity refers to repetitive, perseverative actions that are excessive and inappropriate to a given situation.
For example, an individual with attention-deficit hyperactivity disorder (ADHD) may manifest impulsive problems such as making a statement they regret to a colleague; or jumping a red light; whereas an individual with obsessive-compulsive disorder (OCD) may repeatedly (i.e. compulsively) check the front door is locked, for hours per occasion.
It is well known that impulsive and compulsive problems often occur together in the same individual, but very little is known about processes in the brain that may contribute to this. To address this, in this study supported by the NIHR Cambridge BRC researchers studied brain structure and impulsive-compulsive problems in young adults, and the relationship between them.
They found that most of the occurrence of impulsive and compulsive problems could be explained by difficulty regulating urges and habits, known as ‘disinhibition’. Disinhibition was related to changes in the structure of the brain, especially in regions important for top-down control such as the frontal lobe.
The study identified a new brain-based vulnerability marker contributing to impulsive and compulsive problems. Unlike previous research, the findings go beyond traditional psychiatric diagnostic boundaries, by examining a comprehensive range of behaviors, rather than only one disorder studied in isolation.View publication
Publication: European Respiratory Journal
Anthony W. Martinelli, Tejas Ingle, Joseph Newman, Iftikhar Nadeem, Karl Jackson, Nicholas D. Lane, James Melhorn, Helen E. Davies, Anthony J. Rostron, Aldrin Adeni, Kevin Conroy, Nicholas Woznitza, Matthew Matson, Simon E. Brill, James Murray, Amar Shah, Revati Naran, Samanjit S. Hare, Oliver Collas, Sarah Bigham, Michael Spiro, Margaret M. Huang, Beenish Iqbal, Sarah Trenfield, Stephane Ledot, Sujal Desai, Lewis Standing, Judith Babar, Razeen Mahroof, Ian Smith, Kai Lee, Nairi Tchrakian, Stephanie Uys, William Ricketts, Anant R.C. Patel, Avinash Aujayeb, Maria Kokosi, Alexander J.K. Wilkinson, Stefan J. Marciniak
10 September 2020
Pneumothorax and pneumomediastinum have both been noted to complicate cases of COVID-19 requiring hospital admission. The research team reported the largest case series yet described of patients with both these pathologies that includes non-ventilated patients.
Cases were collected retrospectively from UK hospitals with inclusion criteria limited to a diagnosis of COVID-19 and the presence of either pneumothorax or pneumomediastinum. Patients included in the study presented between March and June 2020. Details obtained from the medical record included demographics, radiology, laboratory investigations, clinical management and survival.
Seventy-one patients from 16 centres were included in the study, of whom 60 patients had pneumothoraces (six also with pneumomediastinum), whilst 11 patients had pneumomediastinum alone.
Survival at 28 days was not significantly different following pneumothorax or isolated pneumomediastinum. The incidence of pneumothorax was higher in males. The 28-day survival was not different between the sexes. Patients above the age of 70 had a significantly lower 28-day survival than younger individuals.
These cases suggest that pneumothorax is a complication of COVID-19. Pneumothorax does not seem to be an independent marker of poor prognosis and the researchers encourage active treatment to be continued where clinically possible.
Anthony Martinelli and Margaret Huang are supported by the Wellcome Trust. Stefan Marciniak is supported by the Medical Research Council, NIHR Cambridge BRC, Royal Papworth Hospital and the Alpha1-Foundation.View publication
Publication: Nature Medicine
Sarah Killcoyne, Eleanor Gregson, David C. Wedge, Dan J. Woodcock, Matthew D. Eldridge, Rachel de la Rue, Ahmad Miremadi, Sujath Abbas, Adrienn Blasko, Cassandra Kosmidou, Wladyslaw Januszewicz, Aikaterini Varanou Jenkins, Moritz Gerstung & Rebecca C. Fitzgerald
07 September 2020
Barrett’s oesophagus is a risk factor for oesophageal cancer. The oesophagus or known as the gullet or food pipe, connects from your mouth to the stomach. Cells within the oesophagus can change and become abnormal. Biopsies taken via an endoscopy can help detect any abnormal cells.
Oesophageal cancer can be hard to detect, Cambridge researchers investigated whether patients could be identified earlier. Using DNA tissue biopsies from patients diagnosed with Barrett’s oesophagus could show which patients are more likely to develop the disease.
Using whole genome sequencing, researchers analysed samples from 88 patients and compared their DNA against control samples collected during clinical surveillance for Barrett’s oesophagus. Researchers looked at the differences in the DNA between patients who were eventually diagnosed with cancer to those who were not. They found several changes and used this model to predict whether a patient was at a high or low risk of cancer.
They found the model could correctly predict oesophageal cancer eight years before diagnosis for half of all patients who went on to develop the disease. This increased to more than three-quarters of patients one to two years before a diagnosis. Read the full story.View publication
Publication: Cell Reports Medicine
Petra Mlcochova, Dami Collier, Allyson Ritchie, Sonny M. Assennato, Myra Hosmillo, Neha Goel, Bo Meng, Krishna Chatterjee, Vivien Mendoza, Nigel Temperton, Leo Kiss, Leo C. James, Katarzyna A. Ciazynska, Xiaoli Xiong, John AG. Briggs, James A. Nathan, Federica Mescia, Laura Bergamaschi, Hongyi Zhang, Petros Barmpounakis, Nikos Demeris, Richard Skells, Paul A. Lyons, John Bradley, Steven Baker, Jean Pierre Allain, Kenneth GC. Smith, Rachel Bousfield, Michael Wilson, Dominic Sparkes, Glenn Amoroso, Effrosyni Gkrania-Klotsas, Susie Hardwick, Adrian Boyle, Ian Goodfellow, Ravindra K. Gupta
1 September 2020
Testing patients for COVID-19 as soon as they arrive at hospital is essential to obtain a diagnosis and to make sure they receive the correct treatment as soon as possible.
In a recent Cambridge study, the use of the SAMBA II test reduced the amount of time patients spent on holding wards. Now Cambridge researchers wanted to go further to create a ‘gold-standard’ method of testing.
The most common form of testing is taking a swab of the nose and throat (known as PCR) to see if the virus is present. However, it can take as long as 14 days for an individual to show symptoms of COVID-19, by which time the virus may have moved from the nose and throat and into the lungs and other tissues and organs, making it harder to detect via a swab test. Another way to detect the virus is looking for antibodies (from blood samples) in individuals.
Cambridge researchers combined the two tests – PCR and the antibody test – to help identify who may have the virus. They found combining both tests was more effective to identify patients who had Covid than those who had just one of the tests. Read the full news story.View publication
Publication: Nature Communications
Varun Warrier, David M. Greenberg, Elizabeth Weir Clara Buckingham, Paula Smith, Meng-Chuan Lai, Carrie Allison, Simon Baron-Cohen
7 August 2020
Transgender and gender-diverse individuals are more likely to be autistic and report higher autistic traits
Researchers reviewed over 600,000 people and used five datasets where participants provided information such as gender identity and if they received a diagnosis of autism or other psychiatric conditions such as depression or schizophrenia. Participants also completed a measure of autistic traits.
Researchers found that transgender and gender-diverse adult individuals were between three and six times more likely to indicate that they were diagnosed as autistic compared to cisgender individuals. The study used data from adults who said they had received an autism diagnosis, however, it is likely there are more individuals on the autistic spectrum who are undiagnosed.
This research will help improve access to mental health care and support for transgender and gender-diverse individuals. Read the full news story.View publication
Publication: JCO Clinical Cancer Informatics
Mireia Crispin-Ortuzar, Marcel Gehrung, Stephan Ursprung, Andrew B. Gill, Anne Y. Warren, Lucian Beer, Ferdia A. Gallagher, Thomas J. Mitchell, Iosif A. Mendichovszky, Andrew N. Priest, Grant D. Stewart, Evis Sala, Florian Markowetz
Cancer is a highly heterogeneous disease. Different parts of a single tumour often look different in medical images; they sometimes even carry different genetic information. This complexity may be key to understanding why some tumours respond better to therapy than others. Once the tumour has been removed through surgery, researchers can obtain tissue samples that allow them to study its spatial composition. However, matching these data to the images that were obtained before surgery is challenging.
The research team developed a computational methodology that relies on 3D printing to automatically design and create tumour moulds that help to match images and tissue accurately without disrupting clinical practice.
Their work provides a robust and automated interface between imaging and tissue, enabling the development of clinical studies to probe tumor heterogeneity on multiple spatial scales. Understanding this heterogeneity may be key to understand why some tumours respond better to therapy than others.View publication
Publication: The Lancet
Prof Rebecca C Fitzgerald, Massimiliano di Pietro, Maria O’Donovan, Roberta Maroni, Beth Muldrew, Irene Debiram-Beecham, Marcel Gehrung, Judith Offman, Monika Tripathi, Samuel G Smith, Benoit Aigret, Fiona M Walter, Prof Greg Rubin, on behalf of theBEST3 Trial team † Prof Peter Sasieni
31 July 2020
Barrett’s oesophagus is a condition that can lead to oesophageal cancer in a small number of people. It’s usually diagnosed in hospital by endoscopy (passing a camera down into the stomach). Samples of cells from any areas that don’t look normal are then collected, but an endoscopy can be uncomfortable and does have some risks.
The Cytosponge test allows the patient to swallow a small capsule with a sponge inside, which is attached to a piece of string. The capsule dissolves after a few minutes, and the sponge inside is released. A nurse then gently pulls the string to remove the sponge. On the way out the sponge collects cells from the lining of the oesophagus. The sample is then taken for analysis using a new laboratory marker called TFF3.
Researchers studied 13,222 participants who were randomly allocated to being offered the sponge test or being looked after by the GP in the usual way. Over the course of a year, the odds of detecting Barrett’s were ten times higher in those who were offered the Cytosponge with 140 cases diagnosed compared to 13 in usual care. In addition, the Cytosponge diagnosed five cases of early cancer (stage 1 and 2), whereas only one case of early cancer was detected in the usual care group.
Alongside better detection, the test means cancer patients can benefit from kinder treatment options if their cancer is caught at a much earlier stage. Read the full news article.
Publication: Cell Reports
Michael C. Lee, Michael S. Nahorski, James R.F. Hockley, Frank Reimann, Ewan St. John Smith, C. Geoffrey Woods
21 July 2020; DOI: 10.1016/j.celrep.2020.107941
Women who don’t need pain relief during childbirth may have a key genetic variant that acts as a natural epidural. Supported by the NIHR Cambridge BRC, researchers investigated why some women experience different levels of pain during childbirth.
Women who did not require any pain relief during the birth of their first child took part in a study to understand their pain threshold. This included applying heat and pressure to their arms and putting their hands in icy water. They were then measured against a control group of women were who were given pain relief during childbirth.
They found the group the women who didn’t need any pain relief had a high pain threshold than those of the control group. Their genetic cold was then sequenced and found these women had a higher-than-expected prevalence of a rare variant of the gene KCNG4. This gene acts as a gate, controlling the electric signal that flows along our nerve cells. This could be the reason why these women did not require pain relief during childbirth. Read the full news articleView publication
Publication: Movement Disorders
Negin Holland, P. Simon Jones, George Savulich, Julie K. Wiggins, Young T. Hong, Tim D. Fryer, Roido Manavaki, Selena Milicevic Sephton, Istvan Boros, Maura Malpetti, Frank H. Hezemans, Franklin I. Aigbirhio, Jonathan P. Coles, John O’Brien, James B. Rowe
11 July 2020
In this study researchers looked at the loss of synapses in two tau-related neurodegenerative diseases (progressive supranuclear palsy and corticobasal syndrome) and the effect of this loss on cognition. The research was done using a novel PET radioligand, [11C]UCB-J.
They found a profound loss of synapses in all areas of the brain, beyond the effect of volume loss. This synaptic loss negatively correlated with disease severity and positively witih cognition.
These findings are key in identifying early steps in the pathology of neurodegeneration, and offer therapeutic targets for future clinical trials.View publication
Publication: Journal of Neurology, Neurosurgery and Psychiatry
Jonathan Tay, Robin G Morris, Anil M Tuladhar, Masud Husain, Frank-Erik de Leeuw, Hugh S Markus
Cerebral small vessel disease (SVD) is the leading vascular cause of dementia and plays a major role in cognitive decline and mortality.
This research aimed to determine whether apathy or depression predicts all-cause dementia in SVD patients.
Using two prospective cohort studies of SVD, the researchers looked at changes in apathy and depression in 104 patients to predict dementia.
The research indicated that while increasing apathy was associated with dementia, baseline depression and change in depression did not predict dementia.
The researchers concluded that apathy, but not depression, may be an early sign of dementia in SVD, and that this may be useful in identifying at-risk individuals.View publication