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.View publication
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: The Lancet Infectious Diseases
Luke W Meredith, William L Hamilton, Ben Warne, Charlotte J Houldcroft, Myra Hosmillo, Aminu S Jahun, Martin D Curran, Surendra Parmar, Laura G Caller, Sarah L Caddy, Fahad A Khokhar, Anna Yakovleva, Grant Hall, Theresa Feltwell, Sally Forrest, Sushmita Sridhar, Michael P Weekes, Prof Stephen Baker, Nicholas Brown, Elinor Moore, Ashley Popay, Iain Roddick, Mark Reacher, Theodore Gouliouris, Prof Sharon J Peacock, Prof Gordon Dougan, M Estée Török, Prof Ian Goodfellow.
14 July 2020
Cambridge researchers have shown how rapid genome sequencing of virus samples and enhanced testing of hospital staff can help to identify clusters of healthcare-associated COVID-19 infections. Read the full news article.View 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
Publication: Journal of Clinical Urology
Vincent J Gnanapragasam, Kelly Leonard, Michal Sut, Cristian Ilie, Jonathan Ord, Jacques Roux, Maria Consuelo Hart Prieto, Anne Warren, Priya Tamer
Prostate cancer is the commonest male cancer and more than one million rectal biopsies for suspected prostate cancer are carried out each year. However, a significant number of men undergoing rectal biopsies develop infection and sepsis.
This study showed that the CamPROBE, a device developed by Cambridge researchers that can be used under local anaesthetic, is just as good at diagnosing prostate cancer as rectal biopsies – with less infection risk.
Led by Cambridge University Hospitals (CUH), the study recruited 40 patients across six sites. CUH developed a user training course and disseminated the method to the other sites, which then offered the Cambridge Prostate Biopsy Device (CamPROBE), as an alternative to transrectal ultrasound guided biopsy to men due for a biopsy as part of their clinical management.
There were no infections, device deficiencies or safety issues reported, and the CamPROBE appears non-inferior in terms of cancer detection rates. The study also showed that the procedure is well tolerated by patients, suited to the local anaesthetic outpatient setting and can be readily disseminated and adopted.
Future clinical investigation trials will aim at confirming the veracity of the findings, develop head-to-head comparisons with other biopsy methods and explore comparative health economic and cost benefit analysis.View publication
Maura Malpetti, Rogier A Kievit, Luca Passamonti, P Simon Jones, Kamen A Tsvetanov, Timothy Rittman, Elijah Mak, Nicolas Nicastro, W Richard Bevan-Jones, Li Su, Young T Hong, Tim D Fryer, Franklin I Aigbirhio, John T O’Brien, James B Rowe
07 May 2020
Alzheimer’s disease is a condition associated with an ongoing decline of the brain functioning correctly. It can affect loss of memory, language and completing everyday tasks.
Researchers having been investigating the brains functionality, and whether they could help clinicians calculate how a patient will progress with their dementia.
Using an imaging machine called PET (positron emission tomography) they were able to take brain scans and detect the build-up of ‘junk proteins’ in the brain alongside brain inflammation and shrinkage. It could help predict how fast or slow and individual will progress with their dementia.
The PET scans could predict faster cognitive decline in patients and they were more accurate predictors than MRI measures of brain shrinkage.View publication
Dami A Collier, Sonny M Assennato, Nyarie Sithole, Katherine Sharrocks, Allyson Ritchie, Pooja Ravji, Matt Routledge, Dominic Sparkes, Jordan Skittrall, Ben Warne, Anna Smielewska, Isobel Ramsey, Neha Goel, Martin Curran, David Enoch, Rhys Tassell, Michelle Lineham, Devan Vaghela, Clare Leong, Hoi Ping Mok, John Bradley, Kenneth Gc Smith, Vivien Mendoza, Nikos Demiris, Martin Besser, Gordon Dougan, Paul J Lehner, Hongyi Zhang, Claire Waddington, Helen Lee, Ravindra K Gupta
03 June 2020
SAMBA II machines were deployed in the ED and holding wards at Addenbrooke’s hospital to help detect COVID-19 in patients as part of a research trial called COVIDx.
Researchers investigated whether using the new machines could accurately provide a faster diagnosis than standard testing practices and review how it would affect patient waiting times.
After collecting nose and throat swabs from over 140 patients, the samples were processed using the SAMBA II machine. Researchers found they were able to provide an accurate diagnostic result within 90 minutes, compared to the standard 24-48-hour lab waiting time. Read the full story.View publication
Publication: Journal of Clinical Endocrinology & Metabolism
Katherine Lawler, Isabel Huang-Doran, Takuhiro Sonoyama, Tinh-Hai Collet, Julia M Keogh, Elana Henning, Stephen O’Rahilly, Leonardo Bottolo, I Sadaf Farooqi
11 May 2020
The hormone leptin is a key regulator of weight. Children who lack leptin (due to changes in the leptin gene) have a very large appetite and rapidly gain weight. After treatment with leptin injections, they can lose weight.
The researchers know that leptin works by reducing their appetite, but they wanted to find out if leptin can affect other metabolic processes around the body too.
They used a cutting-edge technique called metabolomics to simultaneously measure more than 600 metabolic reactions in a single blood sample taken from children and young adults before and after a short period of leptin treatment.
They found that leptin not only caused big shifts in how the body processes fats, but it affected amino acids (which make proteins), bile acids (which can act as cell signals) and steroids (involved in making hormones). These changes overlapped with the changes discovered previously in healthy adults after a period of fasting.
The research findings show that as well as affecting how much food we eat, leptin affects other aspects of our metabolism. This research paves the way for further research into leptin’s action on different cells in the human body.View publication
Lucy Rivett, Sushmita Sridhar, Dominic Sparkes, Matthew Routledge, Nick K. Jones, et al
12 May 2020
Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3-week period (April 2020), 1,032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19) >7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.View publication
James E. D. Thaventhiran, Hana Lango Allen, Kenneth G. C. Smith
06 May 2020
Cambridge researchers sequenced the entire genetic code of 974 people with PID. The team were able to identify variations in genes already known to cause PID. To help identify genetic causes for the remaining participants and other patients with PID, the team used a statistical program known as BeviMed. BeviMed can be used to predict genes that may cause PID, by comparing the genomes of cases and controls. Using this technique, the team were able to identify new genes that cause PID. Full press release hereView publication
Publication: Nature Microbiology
Francesca Gaccioli, Susanne Lager, Marcus C. de Goffau, Ulla Sovio, Justyna Dopierala, Sungsam Gong, Emma Cook, Andrew Sharkey, Ashley Moffett, Wai Kwong Lee, Christian Delles, Cristina Venturini, Judith Breuer, Julian Parkhill, Sharon J. Peacock, D. Stephen Charnock-Jones & Gordon C. S. Smith
4 May 2020
The placenta is the interface between the mum and the fetus and supports the growth of the baby in the womb. Abnormal function of the placenta is associated with poor pregnancy outcome, including maternal and infant diseases and deaths. In turn, placental dysfunction could be due to viral infections, which are known to cause organ failure. We investigated whether viral infection of the placenta is associated with diseases of human pregnancy related to poor placental function, such as pre-eclampsia (hypertensive disorder in the mother) and fetal growth restriction (impaired growth of the fetus during pregnancy).
Using samples from more than 5,000 pregnancies and data available in the literature, we demonstrated that the presence of inherited human herpesvirus 6 (HHV-6) DNA in the feto-placental unit is associated with an increased risk of the mother to develop pre-eclampsia. The virus can be passed to the fetus and the placenta from both the mother and the father. Importantly, our study did not identify any other viral associations with the 2 studied conditions. HHV-6 was the only clear viral signal observed in a large number of placental samples from pathological and normal pregnancies.
Pre-eclampsia is a condition characterized by high maternal blood pressure and protein levels in the urine in the second half of pregnancy. It represents a major determinant of the global burden of disease. Although pre-eclamspia is known to be associated with poor development and function of the placenta, the causes of placental insufficiency are not fully understood. Identifying those will help us to understand and treat this condition, which affects 5-8% of all pregnant women and is responsible for over 75,000 maternal deaths and 500,000 fetal deaths worldwide every year. Our work demonstates that viral infection of the placenta is not a major cause of pre-eclampsia and that a small proportion of cases is likely to be due to the presence of HHV-6 in the feto-placental unit.View publication
Luiza Moore, Daniel Leongamornlert, Tim H. H. Coorens, Mathijs A. Sanders, Peter Ellis, Stefan Dentro, Kevin Dawson, Tim Butler, Raheleh Rahbari, Thomas J Mitchell, Francesco Maura, Jyoti Nangalia, Patrick S. Tarpey, Simon F. Brunner, Henry Lee-Six, Yvette Hooks, Sarah Moody, Krishnaa Mahbubani, Mercedes Jimenez-Linan, Jan J. Brosens, Christine A. Iacobuzio-Donahue, Inigo Martincorena, Kourosh Saeb-Parsy, Peter J. Campbell, Michael R. Stratton
22 April 2020
This paper looks at somatic mutation (changes in the DNA) in healthy human tissue in the endometrium (womb lining) and provides insights into the earliest stages of uterine cancer development, which is the fourth most common cancer in women in the UK.
Many cells in the inner lining of the uterus carry ‘cancer-driving’ mutations that frequently arise early in life. Using whole-genome sequencing to better understand the genetic changes in healthy endometrial tissue, the researchers found that a high proportion of cells carry driver mutations, even though they appear completely normal under the microscope. Furthermore the team found that many of these driver mutations appear to have arisen early in life, in many cases during childhood.View publication