Publications

Publication: Brain

Edward J. Needham,, Alexander L. Ren, Richard J. Digby, Emma J. Norton,  Soraya Ebrahimi, Joanne G. Outtrim, Doris A. Chatfield, Anne E. Manktelow,  Maya M. Leibowitz, Virginia F. J. Newcombe, Rainer Doffinger, Gabriela Barcenas-Morales,  Claudia Fonseca, Michael J. Taussig, Rowan M. Burnstein, Romit J. Samanta,  Cordelia Dunai, Nyarie Sithole, Nicholas J. Ashton, Henrik Zetterberg, Magnus Gisslén, Arden Edén,, Emelie Marklund, Peter J. M. Openshaw, Jake Dunning,  Michael J. Griffiths, Jonathan Cavanagh, Gerome Breen, Sarosh R. Irani,,  Anne Elmer, Nathalie Kingston,, Charlotte Summers,, John R. Bradley,,  Leonie S. Taams, Benedict D. Michael, Edward T. Bullmore, Kenneth G. C. Smith, Paul A. Lyons, Alasdair J. Coles, David K. Menon  and the Cambridge NeuroCOVID Group, the CITIID-NIHR COVID- BioResource Collaboration and Cambridge NIHR Clinical Research Facility

6 September 2022

Summary

COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity.

Researchers investigated the dynamics of, and relationship between, serum markers of brain injury (neurofilament light [NfL], glial fibrillary acidic protein [GFAP] and total tau) and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza.

Publication: Endocrine Connections

Martin Wiegand, David J Halsall, Sarah L Cowan, Kevin Taylor, Robert J B Goudie, Jacobus Preller, Mark Gurnell

26 August 2022

Summary

The renin-angiotensin-aldosterone system (RAAS) is of interest in understanding COVID-19. Using data extracted from CUH Epic, researchers observed profoundly low aldosterone levels (measured using gold-standard mass-spectrometry) in a large proportion of patients with COVID-19, which were not anticipated. The mechanism of this reduction remains obscure with no obvious correlation with obvious explanations. The profoundly low levels have likely not been detected previously since previous studies used immunoassays to measure aldosterone, in which there are high levels of interference in patients with COVID-19.

Publication: Geriatrics

Ben Carter, Victoria L. Keevil, Atul Anand, Christopher N. Osuafor, Robert J. B. Goudie, Jacobus Preller, Matthew Lowry, Sarah Clunie, Susan D. Shenkin, Kathryn McCarthy, Jonathan Hewitt and Terence J. Quinn

24 August 2022

Summary

Assessing frailty in hospital patients is important but it is not clear how best to assess it. Researchers compared two options: the modified Frailty Index [mFI] and the Clinical Frailty Scale [CFS], and assessed how useful each were for predicting death in older adults (≥65 years) in hospital with COVID-19.  Our  work suggests the CFS is better than mFI at predicting death in patients who have COVID-19.

Publication: Science Translational Medicine

Ashwin V. Venkataraman, Ayla Mansurgaia, Rizzo Courtney, Bishop, Yvonne Lewis, Ece Kocagoncu, Anne Lingford-Hughes, Mickael Huibanjan Passchier, James B. Rowe, Hideo Tsukada, David J. Brooks, Laurent Martarello, Robert A. Comley, Laigao Chen, Adam J.Schwarz, Richard Hargreaves, Roger N. Gunn, Eugenii A. Rabiner and Paul M. Matthews

18 August 2022

Summary 

Researchers explored whether widespread cell stress and mitochondrial dysfunction occur in patients with early Alzheimer’s Disease

Publication: Nature Genetics

Foad J. Rouhani, Xueqing Zou, Petr Danecek, Cherif Badja, Tauanne Dias Amarante, Gene Koh, Qianxin Wu, Yasin Memari, Richard Durbin, Inigo Martincorena, Andrew R. Bassett, Daniel Gaffney & Serena Nik-Zainal

11 August 2022

Summary

DNA damage caused by factors such as ultraviolet radiation affect nearly three-quarters of all stem cell lines derived from human skin cells, say Cambridge researchers, who argue that whole genome sequencing is essential for confirming if cell lines are usable. Read the full news story.

Publication: JMRI

Joseph Cheriyan, Alexandra Roberts, Caleb Roberts, Martin J. Graves, Ilse Patterson,Rhys A. Slough,Rosemary Schroyer, Disala Fernando, Subramanya Kumar,Sarah Lee, Geoffrey J.M. Parker, Lea Sarov-Blat, Carmel McEniery, Jessica Middlemiss, Dennis Sprecher, Robert L. Janiczek

27 March 2022

Summary

Lung congestion is common in patients with heart failure. Enhanced MRI may be appropriate method for accurate measurement of lung fluid.

Publication: The Journal of Clinical Endocrinology & Metabolism

Ulla Sovio, Gemma L Clayton, Emma Cook, Francesca Gaccioli, D Stephen Charnock-Jones, Deborah A Lawlor, Gordon C S Smith

18 April 2022

Summary

Currently in the UK, women are selected for diagnostic testing for Gestational Diabetes Mellitus (GDM) based on risk factors such as obesity.  Researchers developed a new predictive test for GDM using metabolomic markers from maternal serum samples, measured at multiple stages of pregnancy. The test was developed using samples from the Pregnancy Outcome Prediction (POP) study and it was externally validated in maternal plasma samples from a demographically highly dissimilar Born in Bradford (BiB) study. Further assessment in the POP study suggested that the predictive ability of a model including the metabolomic markers was clearly better compared to using early pregnancy obesity alone.

Publication: MedRxiv

Natalie E Adams, Amirhossein Jafarian, Alistair Perry, Matthew Rouse, Alexander D Shaw, Alexander G Murley,   Thomas E Cope, W Richard Bevan-Jones, Luca Passamonti, Duncan Street, Negin Holland, David Nesbitt, Laura E Hughes,   Karl J Friston, James RoweNatalie E Adams, Amirhossein Jafarian, Alistair Perry, Matthew Rouse,   Alexander D Shaw, Alexander G Murley, Thomas E Cope, W Richard Bevan-Jones, Luca Passamonti, Duncan Street,   Negin Holland, David Nesbitt, Laura E Hughes, Karl J Friston, James Rowe

23 June 2022

Summary

Synaptic loss occurs early in many neurodegenerative diseases and contributes to cognitive impairment even in the absence of gross atrophy. Currently, for human disease there are few formal models to explain how cortical networks underlying cognition are affected by synaptic loss. Researchers advocate that biophysical models of neurophysiology offer both a bridge from clinical to preclinical models of pathology, and quantitative assays for experimental medicine.

Publication: J Biomech Eng.

Aziz Tokgoz,  Shuo Wang,  Priya Sastry,  Chang Sun, Nichola L. Figg,  Yuan Huang,  Martin R. Bennett, Sanjay Sinha, Jonathan H. Gillard, Michael P. F. Sutcliffe,  Zhongzhao Teng

25 April 2022

Summary

Fiber structures and pathological features, e.g., inflammation and glycosaminoglycan (GAG) deposition, are the primary determinants of aortic mechanical properties which are associated with the development of an aneurysm. This study is designed to quantify the association of tissue ultimate strength and extensibility with the structural percentage of different components, in particular, GAG, and local fiber orientation.

Publication: Nature Communications Biology

Irving L. M. H. Aye, Sungsam Gong, Giulia Avellino, Roberta Barbagallo, Francesca Gaccioli, Benjamin J. Jenkins, Albert Koulman, Andrew J. Murray, D. Stephen Charnock-Jones & Gordon C. S. Smith

15 June 2022

Summary

Placental function and dysfunction differ by sex but the mechanisms are unknown. Researchers show that sex differences in polyamine metabolism are associated with escape from X chromosome inactivation of the gene encoding spermine synthase (SMS).

Publication: BMJ Open

Christian Philip Stickels, Ramesh Nadarajah, Chris P Gale, Houyuan Jiang, Kieran J Sharkey, Ben Gibbison, Nick Holliman, Sara Lombardo, Lars Schewe, Matteo Sommacal, Louise Sun, Jonathan Weir-McCall, Katherine Cheema, James H F Rudd, Mamas Mamas, Feryal Erhun

17 June 2022

Summary

An international team of researchers has modelled the impact that increasing treatment capacity and using a quicker, less invasive treatment option would have on waiting lists. Even in the best-case scenario, they found that the waiting list would take nearly a year to clear.

The traditional treatment for aortic stenosis involves replacing the narrowed valve, most commonly through open heart surgery (a surgical aortic valve replacement, SAVR). However, a newer keyhole procedure called a transcatheter aortic valve implantation (TAVI) is increasingly being used and is now recommended for patients aged 75 and over.

The researchers investigated the impact that increasing treatment capacity and converting a proportion of operations to the quicker TAVI procedure would have on the backlog. They looked at how long it would take to clear the backlog and found that the best and most achievable option involved a combination of increasing capacity by 20 per cent and converting 40 per cent of procedures from SAVR to TAVI. This would clear the backlog within 343 days with 784 deaths while people wait for treatment. Read the full story.

Publication: bioRxiv

Roma Siugzdaite,  Danyal Akarca, Amy Johnson,  Sofia Carozza,  Alexander L Anwyl-Irvine,  Stepheni Uh,  Tess Smith, Giacomo Bignardi,  Edwin Dalmaijer,  Duncan E. Astle

10 June 2022

Summary

The quality of a child’s social and physical environment is a key influence on brain development, educational attainment and mental wellbeing. However, there still remains a mechanistic gap in our understanding of how environmental influences converge on changes in the brain’s developmental trajectory. In a sample of 145 children with structural diffusion tensor imaging data, researchers used generative network modelling to simulate the emergence of whole brain network organisation.

Publication: The Lancet Diabetes and Endocrinology

Nick Wareham, Nita Forouhi

27 October 2021

Summary

Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. Researcgers aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks.

Publication: Elife

Brogan Ashley, Claire Simner, Antigoni Manousopoulou, Carl Jenkinson, Felicity Hey, Jennifer M Frost, Faisal I Rezwan, Cory H White, Emma M Lofthouse, Emily Hyde, Laura DF Cooke, Sheila Barton, Pamela Mahon, Elizabeth M Curtis, Rebecca J Moon, Sarah R Crozier, Hazel M Inskip, Keith M Godfrey, John W Holloway, Cyrus Cooper, Kerry S Jones, Rohan M Lewis, Martin Hewison, Spiros DD Garbis, Miguel R Branco, Nicholas C Harvey, Jane K Cleal

8 March 2022

Summary

This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself.

Publication: Patterns 3: 100506.

Soumya Banerjee, Phil Alsop, Linda Jones, Rudolf N. Cardinal

10 June 2022

Summary

Artificial intelligence (AI) is increasingly taking on a greater role in healthcare. However, hype and negative news reports about AI abound. Integrating patient and public involvement (PPI) in healthcare AI projects may help in adoption and acceptance of these technologies. Researchers argue that AI algorithms should also be co-designed with patients and healthcare workers. They specifically suggest (1) including patients with lived experience of the disease, and (2) creating a research advisory group (RAG) and using these group meetings to walk patients through the process of AI model building, starting with simple (e.g., linear) models.

Publication: Clinical Nutrition

Inge A.L.P. van Beijsterveldt, Pernille Neve Myers, Stuart G. Snowden, Ken K. Ong, Susanne Brix, Anita C.S. Hokken-Koelega, Albert Koulman 

21 April 2022

Summary

Early life is a critical window for adiposity programming and metabolic profile may affect this programming. Researchers investigated if plasma metabolites at age 3 months were associated with fat mass, fat free mass and abdominal subcutaneous and visceral fat outcomes at age 2 years in a cohort of healthy infants and if these associations were different between infants receiving exclusive breastfeeding and those with exclusive formula feeding.

Publication: Journal of the American Heart Association

Paddy C. Dempsey, Tessa Strain, Elisabeth A. H. Winkler, Kate Westgate, Kirsten L. Rennie, Nicholas J. Wareham, Soren Brage, Katrien Wijndaele

26 April 2022

Summary

Emerging evidence suggests accruing sedentary behavior in relatively more prolonged periods may convey additional cardiometabolic risks, but few studies have examined prospective outcomes. Researchers examined the association of sedentary behavior accumulation patterns with incident cardiovascular disease, cancer, and all‐cause mortality.

Publication: International Journal of Epidemiology

Michelle Venables, Caireen Roberts, Kerry Jones, Anila Farooq, Albert Koulman, Nick Wareham, Polly Page

28 May 2022

Since 2008, the Government in the United Kingdom has funded a large, annual survey called the National Diet and Nutrition Survey Rolling Programme (NDNS RP) to collect detailed information from people on the foods they are eating and their nutritional health.

The survey is used to monitor how well the UK population is doing in terms of dietary guidelines and inform the development of new nutrition policies. It is also used to monitor chemical exposure risk to protect food safety. In this NIHR Cambridge BRC paper, the authors have provided easy access to comprehensive information about the NDNS for the academic and wider public health community.

The paper describes the data collected in the first 11 years of the NDNS RP, how it has been used, and demonstrates the scope of publicly available data. The authors present an overview of survey methods to collect and analyse the data.

Between 2008 and 2019, 7999 adults and 7656 children completed food diaries; 4181 adults and 2014 children had a blood sample taken; 3246 adults and 2318 children gave a urine sample and 419 adults and 352 children had their energy expenditure measured. The authors explain how NDNS survey reports and data provide information on the foods, calories and nutrients such as fat, sugar and vitamins consumed by the UK population, and how Government use these data in public health campaigns such as the Change4Life, 5 A DAY and sugar reduction and folate fortification policies.

They also highlight that many other institutions and individuals use the survey including international organisations like the World Health Organisation. Reports are published regularly by Government: https://www.gov.uk/government/collections/national-diet-and-nutrition-survey. Anonymised individual data can be accessed from the Data Service and stored blood and urine samples are available for further research via the NDNS Bioresource.

The NDNS RP provides a unique and valuable publicly available resource for the UK Government, researchers, health professionals and others looking to understand and improve population health and nutrition.

Publication: Nature Neuroscience

Andrea I. Luppi, Pedro A. M. Mediano, Fernando E. Rosas, Negin Holland, Tim D. Fryer, John T. O’Brien, James B. Rowe, David K. Menon, Daniel Bor & Emmanuel A. Stamatakis

26 May 2022

Researchers investigated functional interactions between brain regions into synergistic and redundant components, revealing their information-processing roles.

Publication: HGG Advances

Courtney E. French, Helen Dolling, Karyn Mégy, Alba Sanchis-Juan, Ajay Kumar, Isabelle Delon, Matthew Wakeling, Lucy Mallin, Shruti, Agrawal, Topun Austin, Florence Walston, Soo-Mi Park, Alasdair, Parker, Chinthika Piyasena, Kimberley Bradbury, Sian Ellard, David H.Rowitch, LucyRaymond

24 May 2022

Summary

More than a third of severely sick babies referred for rapid whole genome sequencing received a vital genetic diagnosis. Results from the latest Cambridge genomic study supported by NIHR Cambridge BRC and NIHR BioResource, confirm rapid whole genome sequencing (WGS) as an effective early test to aid diagnosis in severely ill children. Read the full story.