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: European Neuropsychopharmacology

J.R. Breedon, H. Ziauddeen, J. Stochl, K.D. Ersche

24 November 2020


This research investigates the underlying mechanism of addictive behaviour as exemplified by cocaine addiction, and how it impacts on other behaviours such as eating.

Cocaine is adept at being both highly pleasurable and highly habit-forming and both processes are involved in the development of addiction. But are these behavioural changes specific to just cocaine consumption or do they impact other behaviours? This is an interesting question because food consumption is a paradigmatic example of behaviour that can be dominated by both deliberate (so-called goal-directed) and habitual control. As an example, people on diets will exert a high degree of control over their calorific and nutritional intake (‘goal directed’) only to find themselves falling back into old patterns of eating (‘habits’). This is an important question to ask because what we eat has clear and direct consequences for our health; if cocaine addiction has detrimental implications for food consumption, this will have health consequences, beyond the direct consequence of cocaine use.

The researchers presented participants with pictures of food and asked them to rate how much they were willing to pay for them, and how much they wanted to eat the foods. In addition they used questionnaires to investigate both the reasons why cocaine-addicted individuals use cocaine, and the factors influencing their food-related choices.

The results suggest that cocaine addiction narrows the goals of individuals away from ‘normal’ motivators like food, and diverts it towards cocaine. Further, the results suggest that food behaviour in cocaine addiction is more habitual, supporting the hypothesis that the habits developed are wide-reaching and affect behaviours beyond cocaine.

These results will be of interest to those working with individuals with cocaine addiction – they suggest that more attention should be paid to the eating habits of those affected. Further they add support for the ‘habit theory’ of addiction, and suggest that further research into treatments for cocaine addiction should consider the possibility of habits training, that is, methods of directing this ‘habit bias’ towards healthier, more meaningful, activities.

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Publication: Nature Genetics

Praveen Surendran, Joanna M. M. Howson et al

23 November 2020


Increased blood pressure (BP) is a major risk factor for cardiovascular disease (CVD) and related disability worldwide. Identifying biological pathways associated with blood pressure is important to understand the aetiology of CVD.

In this study involving collaborators from across the globe, and participants from diverse ancestries, researchers investigated whether genetic variants that a small proportion of people carry have an impact on blood pressure regulation and more readily implicate the genes underlying blood pressure regulation.

They identified 87 such genetic variants influencing blood pressure regulation that only a small proportion of people carry. In addition to identifying novel candidate genes associated with blood pressure, they showed a potential link between foetal development and an inverse relationship between systolic and diastolic blood pressure with stroke.

As shown in this study, a complex outcome like blood pressure requires large sample sizes to detect genetic variation associated with blood pressure that are rare in humans; studies to date have mainly looked at genetic variants that are carried by many people and therefore have very small effects on blood pressure regulation.

This study contributes to a significant improvement in researchers’ understanding of key genes controlling a risk factor like BP so they can better understand complex diseases like CVD and help identify new blood pressure therapies.

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Publication: Diabetes Care

Ju-Sheng Zheng, Jian’an Luan, Eleni Sofianopoulou, Fumiaki Imamura, Isobel D. Stewart, Felix R. Day, Maik Pietzner, Eleanor Wheeler, Luca A. Lotta, Thomas E. Gundersen, Pilar Amiano, Eva Ardanaz, María-Dolores Chirlaque, Guy Fagherazzi, Paul W. Franks, Rudolf Kaaks, Nasser Laouali, Francesca Romana Mancini, Peter M. Nilsson, N. Charlotte Onland-Moret, Anja Olsen, Kim Overvad, Salvatore Panico, Domenico Palli, Fulvio Ricceri, Olov Rolandsson, Annemieke M.W. Spijkerman, María-José Sánchez, Matthias B. Schulze, Núria Sala, Sabina Sieri, Anne Tjønneland, Rosario Tumino, Yvonne T. van der Schouw, Elisabete Weiderpass, Elio Riboli, John Danesh, Adam S. Butterworth, Stephen J. Sharp, Claudia Langenberg, Nita G. Forouhi, Nicholas J. Wareham

17 November 2020


Summary:

Type 2 is a condition with serious health problems. Previous research has shown higher blood levels of vitamin C were linked with lower future risk of type 2 diabetes and if this was proven, it could mean that giving vitamin C as a supplement may help in preventing the condition. Testing this theory is quite challenging due to finding the correct dose.

Researchers identified 11 genetic markers that can predict blood levels of vitamin C using a large sample of more than 50,000 adults. They tested the association of type 2 diabetes with genetically predicted vitamin C levels with a large sample size of more than 80,000 people with diabetes and up-to 840,000 people without diabetes.

They found a mismatch when comparing the link of diabetes with the genetically predicted vitamin C levels versus when used directly measured blood vitamin C levels. The researchers results for directly measured or genetically predicted blood vitamin C levels indicated that blood vitamin C is not likely to be a causal factor for the development of type diabetes. Therefore conclude that it is not justified to use vitamin C supplementation for the prevention of type 2 diabetes.

Researchers highlighted that the current research findings should be interpreted as showing no link of the micronutrient vitamin C with type 2 diabetes.

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Publication: Alzheimer's and Dementia

Kamen A. Tsvetanov, Stefano Gazzina, P. Simon Jones, John van Swieten, Barbara Borroni, Raquel Sanchez‐Valle, Fermin Moreno, James B. Rowe et al

20 November 2020


The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. The research team investigate this phenomenon in familial frontotemporal dementia (FTD).

There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, the researchers identified behaviorally relevant structural and functional network differences. Structure‐function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non‐carriers, and increased with proximity to the expected onset of disease.

The findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance.

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Publication: Neurobiology of Aging

Elijah Mak, Nicolas Nicastro, Maura Malpetti, George Savulich, Ajenthan Surendranathan, Negin Holland, Luca Passamonti, Simon P. Jones, Stephen F. Carter, Li Su Young T.Hong, Tim D.Fryer, Guy B. Williams, Franklin Aigbirhio, James B. Rowe & John T. O’Brien

14 November 2020


Alzheimer’s disease (AD) pathology is frequently observed as a comorbidity in people with dementia with Lewy bodies (DLB). Here, the research team evaluated the in vivo distribution of tau burden and its influence on the clinical phenotype of DLB.

Tau deposition was quantified using [18F]-AV1451 positron emission tomography in people with DLB (n = 11) and AD (n = 27), and healthy controls (n = 14). A subset of subjects with Lewy body diseases (n = 4) also underwent [11C]-PK11195 PET to estimate microglial activation. [18F]-AV1451 BPND was lower in DLB compared to AD across widespread regions. The medial temporal lobe [18F]-AV1451 BPND distinguished people with DLB from AD (AUC = 0.87), and negatively correlated with ACE-R and MMSE. There was a high degree of colocalisation between [18F]-AV1451 and [11C]-PK11195 binding (p<0.001).

The findings of minimal tau burden in DLB confirm previous studies. Nevertheless, the associations of [18F]-AV1451 binding with cognitive impairment, suggest that tau may interact synergistically with other pathological processes to aggravate disease severity in DLB.

 

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Publication: Nordic Journal of Psychiatry

Josefine Freyberg , Søren Brage , Lars Vedel Kessing & Maria Faurholt-Jepsen

14 October 2020


Summary:

The subjective reporting of physical activity generally has low accuracy for quantifying energy expenditure, possibly due to problems of recall which may differ by mental health status.

This study compared the validity of self-reported physical activity (using International Physical Activity Questionnaire, IPAQ) in patients with bipolar disorder, unaffected relatives and healthy controls using combined heart rate and movement sensing as the objective criterion measure.

Correlations were positive but weak between IPAQ and sensor-based estimates for all groups combined, indicating IPAQ may be used to approximately rank individuals by activity level but there was no clear evidence that validity was any different in the bipolar patients as validity in the two comparison groups was higher (unaffected relatives) and lower (healthy controls).

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Publication: Brain A Journal of Neurology

Alexander G Murley, Matthew A Rouse, P Simon Jones, Rong Ye, Frank H Hezemans, Claire O’Callaghan, Polytimi Frangou, Zoe Kourtzi, Catarina Rua, T Adrian Carpenter, Christopher T Rodgers, James B Rowe

3 November 2020


Behavioural disinhibition is a common feature of the syndromes associated with frontotemporal lobar degeneration (FTLD). It is associated with high morbidity and lacks proven symptomatic treatments. A potential therapeutic strategy is to correct the neurotransmitter deficits associated with FTLD, thereby improving behaviour. Reductions in the neurotransmitters glutamate and GABA correlate with impulsive behaviour in several neuropsychiatric diseases and there is post-mortem evidence of their deficit in FTLD. Here, the researchers tested the hypothesis that prefrontal glutamate and GABA levels are reduced by FTLD in vivo, and that their deficit is associated with impaired response inhibition.

They measured glutamate and GABA levels using semi-LASER magnetic resonance spectroscopy in the right inferior frontal gyrus, because of its strong association with response inhibition, and in the primary visual cortex, as a control region. The stop-signal reaction time was calculated using an ex-Gaussian Bayesian model. Participants with frontotemporal dementia and progressive supranuclear palsy had impaired response inhibition, with longer stop-signal reaction times compared with controls. GABA concentration was reduced in patients versus controls in the right inferior frontal gyrus, but not the occipital lobe. There was no group-wise difference in partial volume corrected glutamate concentration between patients and controls. Both GABA and glutamate concentrations in the inferior frontal gyrus correlated inversely with stop-signal reaction time, indicating greater impulsivity in proportion to the loss of each neurotransmitter.

The researchers conclude that the glutamatergic and GABAergic deficits in the frontal lobe are potential targets for symptomatic drug treatment of frontotemporal dementia and progressive supranuclear palsy.

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Publication: Journal of Neurology, Neurosurgery & Psychiatry

Maura Malpetti, Timothy Rittman, Peter Simon Jones, Thomas Edmund Cope, Luca Passamonti, William Richard Bevan-Jones, Karalyn Patterson, Tim D Fryer, Young T Hong, Franklin I Aigbirhio, John Tiernan O’Brien, James Benedict Rowe

29 October 2020


The researchers report in vivo patterns of neuroinflammation and abnormal protein aggregation in seven cases of familial frontotemporal dementia (FTD) with mutations in MAPT, GRN and C9orf72 genes.

Patients with familial FTD across all mutation groups showed increased [11C]PK11195 binding predominantly in frontotemporal regions, with additional regions showing abnormalities in individuals. Patients with MAPT mutations had a consistent distribution of [18F]AV-1451 binding across the brain, with heterogeneous distributions among carriers of GRN and C9orf72 mutations.

This case series suggests that neuroinflammation is part of the pathophysiology of familial FTD, warranting further consideration of immunomodulatory therapies for disease modification and prevention.

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Publication: MedRxiV

Christopher J. R. Illingworth, ProfileWilliam L. Hamilton,  ProfileChris Jackson, Ashley Popay, Luke Meredith, Charlotte J. Houldcroft, Myra Hosmillo, Aminu Jahun, Matthew Routledge, Ben Warne, Laura Caller, Sarah Caddy, Anna Yakovleva, Grant Hall, Fahad A. Khokhar, Theresa Feltwell, Malte L. Pinckert, Iliana Georgana, Yasmin Chaudhry, Martin Curran, Surendra Parmar, Dominic Sparkes, Lucy Rivett, Nick K. Jones, Sushmita Sridhar, Sally Forrest, Tom Dymond, Kayleigh Grainger, Chris Workman, Effrossyni Gkrania-Klotsas, Nicholas M. Brown, Michael P. Weekes, Stephen Baker, Sharon J. Peacock, Theodore Gouliouris, Ian Goodfellow, Daniela de Angelis, M. Estée Török

27 October 2020


Summary:

A new software tool will help doctors identify where cases of COVID-19 were caused by transmission within a hospital, helping them to prevent further spread of the disease.

The new software package, A2B-Covid, combines knowledge about infection dynamics, data describing the movements of individuals, and genome sequence data to assess whether or not coronavirus has been transmitted between people in the hospital environment.

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Publication: International Journal of Stroke

Stefania Nannoni , Rosa de Groot, Steven Bell, Hugh S Markus

26 October 2020


Summary:

Fourteen out of every 1,000 COVID-19 patients admitted to hospital experience a stroke, a rate that is even higher in older patients and those with severe infection and pre-existing vascular conditions.

A team of researchers at the Stroke Research Group, carried out a systematic review and meta-analysis of published research into the link between COVID-19 and stroke. In total, the researchers analysed 61 studies, covering more than 100,000 patients admitted to hospital with COVID-19. The researchers found that stroke occurred in 14 out of every 1,000 cases. The most common manifestation was acute ischemic stroke, which occurred in just over 12 out of every 1,000 cases. Brain haemorrhage was less common, occurring in 1.6 out of every 1,000 cases. Most patients had been admitted with COVID-19 symptoms, with stroke occurring a few days later.

Read the full news story

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Publication: Small

Sunjie Ye, Arsalan A. Azad, Joseph E. Chambers, Alison J. Beckett, Lucien Roach, Samuel C. T. Moorcroft, Zabeada Aslam, Ian A. Prior, Alexander F. Markham, P. Louise Coletta, Stefan J. Marciniak, Stephen D. Evans

25 October 2020


Summary:

More than 2,600 people are diagnosed in the UK each year with mesothelioma, a malignant form of cancer caused by exposure to asbestos and can be hard to treat.

In a collaboration between the University of Cambridge and University of Leeds, researchers have developed a form of gold nanotubes whose physical properties are ‘tunable’ – in other words, the team can tailor the wall thickness, microstructure, composition, and ability to absorb particular wavelengths of light.

The researchers added the nanotubes to mesothelioma cells cultured in the lab and found that they were absorbed by the cells, residing close to the nucleus, where the cell’s DNA lies. When the team targeted the cells with a laser, the nanotubes absorbed the light and heated up, killing the mesothelioma cell.

Read the full press release

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Publication: Movement Disorders

Samuel Shribman, Carolin Heller, Maggie Burrows, Amanda Heslegrave,Imogen Swift, Martha S. Foiani, Godfrey T. Gillett, Emmanuel A. Tsochatzis, James B. Rowe et al

20 October 2020


Outcomes are unpredictable for neurological presentations of Wilson’s disease (WD). Dosing regimens for chelation therapy vary and monitoring depends on copper indices, which do not reflect end‐organ damage. The objective was to identify a biomarker for neurological involvement in WD.

Unlike copper indices, neurofilament light (NfL) concentrations were higher in neurological than hepatic presentations. They were also higher in those with active neurological disease when controlling for severity and correlated with neurological examination subscores in stable patients.

NfL is a biomarker of neurological involvement with potential use in guiding chelation therapy and clinical trials for novel treatments.

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