Publications

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

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Publication: BMJ Journal of Neurology, Neurosurgery and Psychiatry

Leonidas Chouliaras, Alan Thomas, Maura Malpetti, Paul Donaghy, Joseph Kane, Elijah Mak, George Savulich, Maria A Prats-Sedano, Amanda J Heslegrave, Henrik Zetterberg, Li Su, James Benedict Rowe, John O’Brien

27 January 2022


Summary

This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer’s disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). This large study shows the role of plasma biomarkers in differentiating patients with different dementias, and at monitoring longitudinal change.

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Publication: bioRxiv

Bo Meng, Isabella A.T.M Ferreira, Adam Abdullahi, Steven A. Kemp, Niluka Goonawardane, Guido Papa, Saman Fatihi, Oscar J. Charles, Dami A. Collier, CITIID-NIHR BioResource COVID-19 Collaboration, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Jinwook Choi, Joo Hyeon Lee, Petra Mlcochova, Leo James, Rainer Doffinger, Lipi Thukral, Kei Sato,  View ORCID ProfileRavindra K. Gupta

21 December 2021


Summary

As the SARS-CoV-2 virus replicates and spreads, errors in its genetic code can lead to changes in the virus. Working in secure conditions, researchers created synthetic viruses – known as ‘pseudoviruses’ – that carried key mutations found in the Delta and Omicron strains. They used these to study the virus’s behaviour.

They tested the pseudoviruses against blood samples donated to the NIHR COVID-19 BioResource. The blood samples were from vaccinated individuals who had received two doses of either the AstraZeneca (ChAdOx-1) or Pfizer (BNT162b2) vaccines. Read the full story.

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Publication: New England Journal of Medicine

Julia Ware,  Janet M. Allen, Charlotte K. Boughton, Malgorzata E. Wilinska, Sara Hartnell, Ajay Thankamony, Carine de Beaufort, Ulrike Schierloh, Elke Fröhlich-Reiterer, Julia K. Mader, Thomas M. Kapellen, Birgit Rami-Merhar, Martin Tauschmann, Katrin Nagl, Sabine E. Hofer, Fiona M. Campbell, James Yong, Korey K. Hood, Julia Lawton, Stephane Roze, Judy Sibayan, Laura E. Bocchino, Craig Kollman, and Roman Hovorka

20 January 2022


Summary

In this multicenter, randomized, crossover trial, researchers recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy. Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy (control). Read the full press release.

 

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Publication: International Journal of Obesity

Tim Lindsay, Katrien Wijndaele, Kate Westgate, Paddy Dempsey, Tessa Strain, Emanuella De Lucia Rolfe, Nita G. Forouhi, Simon Griffin, Nick J. Wareham & Søren Brage

30 September 2021


Summary

Physical activity energy expenditure (PAEE) represents the total volume of all physical activity. This can be accumulated as different underlying intensity profiles. Although volume and intensity have been studied in isolation, less is known about their joint association with health. Researchers examined this association with body fatness in a population-based sample of middle-aged British adults.

 

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Publication: Journal of Neurotrauma

Jeanette Tas, Erta Beqiri, Ruud C. van Kaam, Marek Czosnyka, Joseph Donnelly, Roel H. Haeren, Iwan C.C. van der Horst, Peter J. Hutchinson, Sander M.J. van Kuijk, Analisa L. Liberti, David K. Menon, Cornelia W.E. Hoedemaekers, Bart Depreitere, Peter Smielewski, Geert Meyfroidt, Ari Ercole, and Marcel J.H. Aries

12 October 2021


Summary

Managing traumatic brain injury (TBI) patients with a cerebral perfusion pressure (CPP) near to the cerebral autoregulation (CA)-guided “optimal” CPP (CPPopt) value is associated with improved outcome and might be useful to individualize care, but has never been prospectively evaluated.

This study evaluated the feasibility and safety of CA-guided CPP management in TBI patients requiring intracranial pressure monitoring and therapy (TBIicp patients).

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Publication: Psychological Medicine

Katherine Parkin; Shanquan Chen; Marjan Biria; Helen Beckwith; Isaac Jarratt-Barnham; Naomi A Fineberg; Rudolf N Cardinal; Trevor W Robbins; Emilio Fernandez-Egea

13 January 2022


The paper explores the impact of obsessive-compulsive symptoms (OCS) on the wellbeing of people who take clozapine to manage symptoms of schizophrenia. It highlights that clozapine-associated OCS occur frequently in this group of patients and that these symptoms have a negative impact on people’s wellbeing over time.

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Publication: Medrxiv

EJ Needham, AL Ren, RJ Digby, JG Outtrim, DA Chatfield, AE Manktelow, VFJ Newcombe, R Doffinger, G Barcenas-Morales, C Fonseca, MJ Taussig, RM Burnstein, C Dunai, N Sithole, NJ Ashton, H Zetterberg, M Gisslen, A Edén, E Marklund, MJ Griffiths, J Cavanagh, G Breen,  View ORCID ProfileSR Irani, A Elmer, N Kingston, JR Bradley, LS Taams,  View ORCID ProfileBD Michael, ET Bullmore, KGC Smith, PA Lyons, AJC Coles, DK Menon, the Cambridge Neuro COVID Group, the NIHR COVID-19 BioResource, Cambridge NIHR Clinical Research Facility

5 December 2021


Summary

COVID-19 has been associated with many neurological complications including stroke, delirium and encephalitis. But it is unknown the full neurological injury Covid-19 has caused.

Researchers investigated the dynamics of, and relationship between, serum markers of brain injury and markers of dysregulated host response including measures of autoinflammation (proinflammatory cytokines) and autoimmunity.

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Publication: ESC Heart Failure

Faye Forsyth, James Brimicombe, Joseph Cheriyan, Duncan Edwards, F. D. Richard Hobbs, Navazh Jalaludeen, Jonathan Mant, Mark Pilling, Rebekah Schiff, Clare J. Taylor,M. Justin Zaman, Christi Deaton

21 September 2021


Summary

This paper illustrates the challenges of finding patients with heart failure with preserved ejection fraction (HFpEF) in primary care, and that many patients with likely HFpEF will not have their diagnosis confirmed. Greater awareness of HFpEF in primary care and improved diagnostic pathways are needed.

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Publication: BJGP Open

Faye ForsythJames BrimicombeJoseph CheriyanDuncan EdwardsFD Richard HobbsNavazh JalaludeenJonathan MantMark PillingRebekah SchiffClare J TaylorM Justin ZamanChristi Deaton

14 December 2021


Summary

Compared with patients with other heart failure diagnoses in primary care, those with heart failure with preserved ejection fraction (HFpEF) are more likely to be women, obese, prefrail/frail, more functionally impaired and report more symptoms.

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Publication: European Journal of Cardiovascular Nursing

Helen Lin, Peter Hartley, Faye Forsyth, Mark Pilling, F D Richard Hobbs, Clare J Taylor, Rebekah Schiff, Christi Deaton

9 April 2021


Summary

This is a baseline analysis of physical activity (measured by accelerometer) of 124 patients, comparing those with confirmed heart failure with preserved ejection fraction (HFpEF) and those without  HFpEF but with other HF diagnoses.

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Publication: British Journal of Nutrition

L.E.T. Vissers, I. Sluijs, S. Burgess, N.G. Forouhi,H. Freisling, F. Imamura, T.K. Nilsson, F. Renström, E. Weiderpass, K. Aleksandrova, C.C. Dahm, A. Perez-Cornago, M.B. Schulze, T.Y.N. Tong, D. Aune, C. Bonet, J.M.A. Boer, H. Boeing, M.D. Chirlaque, M.I. Conchi, L. Imaz, S. Jäger, V. Krogh, C. Kyrø, G. Masala,O. Melander, K. Overvad, S. Panico, M.J. Sánches, E. Sonestedt, A. Tjønneland, I. Tzoulaki, W.M.M. Verschuren, E. Riboli, N.J. Wareham, J. Danesh, A.S. Butterworth, Y.T. van der Schouw

21 October 2021


Higher milk intake has been associated with a lower stroke risk, but not with risk of coronary heart disease (CHD). Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses.

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Publication: Journal of the American Heart Association

Marinka Steur, Laura Johnson, Stephen J. Sharp, Fumiaki Imamura, Ivonne Sluijs, Timothy J. Key, Angela Wood, Rajiv Chowdhury, Marcela Guevara, Marianne U. Jakobsen, Ingegerd Johansson, Albert Koulman, Kim Overvad, Maria‐José Sánchez, Yvonne T. van der Schouw, Antonia Trichopoulou, Elisabete Weiderpass, Maria Wennberg, Ju‐Sheng Zheng, Heiner Boeing, Jolanda M. A. Boer, Marie‐Christine Boutron‐Ruault, Ulrika Ericson, Alicia K. Heath, Inge Huybrechts, Liher Imaz, Rudolf Kaaks, Vittorio Krogh, Tilman Kühn, Cecilie Kyrø, Giovanna Masala, Olle Melander, Conchi Moreno‐Iribas, Salvatore Panico, José R. Quirós, Miguel Rodríguez‐Barranco, Carlotta Sacerdote, Carmen Santiuste, Guri Skeie, Anne Tjønneland, Rosario Tumino, W. M. Monique Verschuren, Raul Zamora‐Ros, Christina C. Dahm, Aurora Perez‐Cornago, Matthias B. Schulze, Tammy Y. N. Tong, Elio Riboli, Nicholas J.Wareham, John Danesh, Adam S. Butterworth, and Nita G. Forouhi

7 December 2021


Summary

Once thought to be the best dietary advice for the prevention of heart attacks, reducing saturated fat in the diet is increasingly questioned as a strategy for improving heart health. This change, which is evident in the increasing popularity of low carbohydrate, not low fat diets, is happening for a variety of reasons.

Researchers conducted research across nine countries of Europe testing the link between different types of dietary fats and the future risk of developing heart disease. This study involved 10,529 people who developed heart disease over time and compared them with 16,730 people who did not develop heart disease, who were randomly selected from 385,747 European Prospective Investigation into Cancer (EPIC) study volunteers in the EPIC-CVD Study.

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Publication: Lancet Regional Health Europe

Tessa Strain, Stephen  J.Sharp, Andrew Spiers, Helen Price, Ciara Williams, Carol Fraser, Søren Brage, Katrien Wijndaele, Paul Kelly

29 November 2021


Summary

To limit the spread of COVID-19 in March 2020, the population of England was instructed to stay home, leaving only for essential shopping, health-care, work, or exercise. The impact on population activity behaviours is not clear. Researchers describe changes in duration and types of activity undertaken by adults ≥16 years in England between March and May 2016 and 2020, by socio-demographic strata. Restrictions introduced in Spring 2020 likely reduced physical activity levels in England. The magnitude of the declines were not uniform by demographic groups or by activity type, which future policies should consider.

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Publication: The Journal of Clinical Endocrinology & Metabolism

Ulla Sovio, Neil Goulding, Nancy McBride, Emma Cook, Francesca Gaccioli,  Stephen Charnock-Jones, Deborah A Lawlor, Gordon C S Smith, 

19 November 2021


Summary

Large size at birth is associated with complications in the mother and the baby. Alongside work in fetal growth restriction (FGR), researchers analysed their previously developed metabolite ratio in relation to large for gestational age (LGA) infants born at term.

They found that the metabolite ratio predictive of FGR was inversely associated with both LGA and birth weight z score as a continuous trait. These findings, obtained from the Pregnancy Outcome Prediction study, were externally validated in the Born in Bradford study.

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Publication: Nature

Stephen-John Sammut, Mireia Crispin-Ortuzar, Suet-Feung Chin, Elena Provenzano, Helen A. Bardwell, Wenxin Ma, Wei Cope, Ali Dariush, Sarah-Jane Dawson, Jean E. Abraham, Janet Dunn, Louise Hiller, Jeremy Thomas, David A. Cameron, John M. S. Bartlett, Larry Hayward, Paul D. Pharoah, Florian Markowetz, Oscar M. Rueda, Helena M. Earl & Carlos Caldas

7 December 2021


Summary

Breast cancers are complex ecosystems of malignant cells and tumour microenvironment.

The composition of these tumour ecosystems and interactions within them contribute to cytotoxic therapy response. Researchers collected clinical, digital pathology, genomic and transcriptomic profiles of pre-treatment biopsies of breast tumours from 168 patients treated with chemotherapy +/- HER2-targeted therapy prior to surgery.

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Publication: npj Schizophrenia

Banerjee S, Liò P, Jones PB, Cardinal RN

8 December 2021


Summary

Machine learning (ML), one aspect of artificial intelligence (AI), involves computer algorithms that train themselves. They have been widely applied in the healthcare domain. However, many trained ML algorithms operate as ‘black boxes’, producing a prediction from input data without a clear explanation of their workings.

Researchers apply class-contrastive counterfactual reasoning to ML to demonstrate how specific changes in inputs lead to different predictions of mortality in people with severe mental illness (SMI).

Researchers produce predictions accompanied by visual and textual explanations as to how the prediction would have differed given specific changes to the input.

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Publication: Nature Metabolism

Scott C. Ritchie, Samuel A. Lambert, Matthew Arnold, Shu Mei Teo, Sol Lim, Petar Scepanovic, Jonathan Marten, Sohail Zahid, Mark Chaffin, Yingying Liu, Gad Abraham, Willem H. Ouwehand, David J. Roberts, Nicholas A. Watkins, Brian G. Drew, Anna C. Calkin, Emanuele Di Angelantonio, Nicole Soranzo, Stephen Burgess, Michael Chapman, Sekar Kathiresan, Amit V. Khera, John Danesh, Adam S. Butterworth & Michael Inouye

8 November 2021


Summary

For the first time, scientists have used polygenic scoring to identify molecular drivers of cardiovascular disease and diabetes, which could be targeted to help prevent or treat some of these conditions.

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Publication: NEJM Evidence

Tian X. Zhao, Rouchelle S. Sriranjan, Zewen Kelvin Tuong, Yuning Lu, Andrew P. Sage, Meritxell Nus, Annette Hubsch, Fotini Kaloyirou, Evangelia Vamvaka, Joanna Helmy, Michalis Kostapanos, Navazh Jalaludeen, David Klatzmann, Alain Tedgui, James H.F. Rudd, Sarah J. Horton, Brian J.P. Huntly, Stephen P. Hoole, Simon P. Bond,  Menna R. Clatworthy, Joseph Cheriyan, and Ziad Mallat,

22 November 2021


Summary

Atherosclerosis is a chronic inflammatory disease of the artery wall. Regulatory T cells (Tregs) limit inflammation and promote tissue healing. Low doses of interleukin (IL)-2 have the potential to increase Tregs, but its use is contraindicated for patients with ischemic heart disease.

In a randomized, double-blind, placebo-controlled, dose-escalation trial, researchers tested low-dose subcutaneous aldesleukin (recombinant IL-2), given once daily for 5 consecutive days.

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Publication: Journal of Nuclear Medicine

Maura Malpetti, Sanne S Kaalund, Kamen A Tsvetanov, Timothy Rittman, Mayen Briggs, Kieren Allinson, Luca Passamonti, Negin Holland, P Simon Jones, Tim D Fryer, Young T Hong, Antonina Kouli, Richard Bevan-Jones, Elijah Mak, George Savulich, Maria Grazia Spillantini, Franklin Aigbirhio, Caroline H Williams-Gray, John T O’Brien and James B Rowe

18 November 2021


Summary

Progressive brain diseases like dementia and Parkinson’s disease move through stages. A new system to stage the dementia-parkinsonian disease known as Progressive Supranuclear Palsy (PSP) has been developed in 2020.  In 2021, researchers validated the new scheme at the Cambridge Brain Bank, looking at the disease severity at the end of life. Researchers wanted to know how the disease progresses and to stop it.

Researchers used a PET scan with a chemical “dye” called 18F-flortaucipi to measure PSP. Despite high hopes for PET using this dye to measure the burden of PSP, when the study began, the results of the study are clear – it does not support the staging of disease, either in lifetime or in terms of outcomes of the illness. 18F-Flortaucipir PET is successfully used in other diseases, like Alzheimer’s, but it cannot be used for PSP staging.

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Publication: BMJ

Katherine R Schon, Rita Horvath, Wei Wei, Claudia Calabrese, Arianna Tucci, Kristina Ibañez, Thiloka Ratnaike, Robert D S Pitceathly, Enrico Bugiardini, Rosaline Quinlivan, Michael G Hanna, Emma Clement, Emma Ashton, John A Sayer, Paul Brennan, Dragana Josifova, Louise Izatt, Carl Fratter, consultant Victoria Nesbitt, Timothy Barrett, Dominic J McMullen, Audrey Smith, Charulata Deshpande, Sarah F Smithson, Richard Festenstein, Natalie Canham, Mark Caulfield, Henry Houlden, Shamima Rahman, Patrick F Chinnery

4 November 2021


Summary

Mitochondrial disorders affect around 1 in 4,300 people and cause progressive, incurable diseases. They are amongst the most common inherited diseases but are difficult for clinicians to diagnose, standard tests can fail to diagnose some patients. A new study has been able to find using WGS can help provide a diagnosis for up to 31% more  patients with a rare genetic disorder which will ultimately help them begin the right treatment pathway.

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