Dopamine D2-like receptor stimulation selectively blocks learning from losses in visual and spatial reversal learning in the rat: behavioural and computational evidence
Alsiö J, Phillips BU, Sala Bayo J, Nilsson SRO, Calafat-Pla TC, Rizwand A, Plumbridge J, López-Cruz L, Dalley JW, Cardinal RN, Mar AC, Robbins TW
19 June 2019
Dopamine D2-like receptors (D2R) are important drug targets in schizophrenia and Parkinson’s disease, but D2R ligands also cause cognitive inflexibility such as poor reversal learning. The specific role of D2R in reversal learning remains unclear.
Here researchers tested the hypotheses that D2R agonism impairs reversal learning by blocking negative feedback and that antagonism of D1-like receptors (D1R) impairs learning from positive feedback.
Male Lister Hooded rats were trained on a novel visual reversal learning task. Performance on “probe trials”, during which the correct or incorrect stimulus was presented with a third, probabilistically rewarded (50% of trials) and therefore intermediate stimulus, revealed individual learning curves for the processes of positive and negative feedback.
The effects of D2R and D1R agonists and antagonists were evaluated. A separate cohort was tested on a spatial probabilistic reversal learning (PRL) task after D2R agonism.
Computational reinforcement learning modelling was applied to choice data from the PRL task to evaluate the contribution of latent factors.
The team found that D2R agonism with quinpirole dose-dependently impaired both visual reversal and PRL. Analysis of the probe trials on the visual task revealed a complete blockade of learning from negative feedback at the 0.25 mg/kg dose, while learning from positive feedback was intact. Estimated parameters from the model that best described the PRL choice data revealed a steep and selective decrease in learning rate from losses. D1R antagonism had a transient effect on the positive probe trials. They concluded that D2R stimulation impairs reversal learning by blocking the impact of negative feedback.
Mortality rates and proximal causes of death in patients with Lewy body dementia versus Alzheimer’s disease: A longitudinal study using secondary care mental health records
Publication: International Journal Geriatric Psychiatry
Anne D. Kershenbaum, Annabel C. Price, Rudolf N. Cardinal, Shanquan Chen, James M. Fitzgerald, Jonathan Lewis, Sinéad Moylett, John T. O’Brien
19 May 2023
Survival is shorter in Lewy body dementia (LBD, referring to both Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB)) compared with Alzheimer’s disease (AD), but the reasons for this difference are not well established.
Researchers identified cohorts of patients with dementia (male and female AD, PDD, and DLB dementia groups) referred into mental health services and linked to National Health Service (NHS) Hospital Episode Statistics and the Office for National Statistics to identify death dates and proximal cause of death. Among patients with DLB and PDD compared to AD ,those with PDD, especially males with PDD, had the highest hazard ratio for death. Aspiration pneumonia and nervous system causes of death accounted for a significant proportion of the excess deaths in the male PDD group compared to the male AD group. Compared with AD, hazard ratios for nervous system causes of death were significantly elevated in all LBD groups. A range of cause‐of‐death categories were significantly more frequent across the LBD groups, with aspiration pneumonia ,genitourinary causes and other respiratory causes elevated in more than one groupView publication
Publication: Nature Medicine
Agatha A. van der Klaauw, Emily C. Horner, Pehuén Pereyra-Gerber, Utkarsh Agrawal, William S. Foster, Sarah Spencer, Bensi Vergese, Miriam Smith, Elana Henning, Isobel D. Ramsay, Jack A. Smith, Stephane M. Guillaume, Hayley J. Sharpe, Iain M. Hay, Sam Thompson, Silvia Innocentin, Lucy H. Booth, Chris Robertson, Colin McCowan, Steven Kerr, Thomas E. Mulroney, Martin J. O’Reilly, Thevinya P. Gurugama, Lihinya P. Gurugama, Maria A. Rust, Alex Ferreira, Soraya Ebrahimi, Lourdes Ceron-Gutierrez, Jacopo Scotucci, Barbara Kronsteiner, Susanna J. Dunachie, Paul Klenerman, PITCH Consortium, Adrian J. Park, Francesco Rubino, Abigail A. Lamikanra, Hannah Stark, Nathalie Kingston, Lise Estcourt, Heli Harvala, David J. Roberts, Rainer Doffinger, Michelle A. Linterman, Nicholas J. Matheson, Aziz Sheikh, I. Sadaf Farooqi & James E. D. Thaventhiran
11 May 2023
Clinical trials have shown that COVID-19 vaccines are highly effective at reducing symptoms, hospitalisation and deaths caused by the virus, including for people with obesity. Previous studies have suggested that antibody levels may be lower in vaccinated people who have obesity and that they may remain at higher risk of severe disease than vaccinated people with normal weight. The reasons for this have, however, remained unclear. Read the news story.View publication
Publication: New England Journal of Medicine
Peter J. Hutchinson, Hadie Adams, Midhun Mohan, Bhagavatula I. Devi, Christopher Uff, Shumaila Hasan, Harry Mee, Mark H. Wilson, Deepak K. Gupta, M.Ch, Diederik Bulters, Ardalan Zolnourian, Catherine J. McMahon, Matthew G. Stovell, Yahia Z. Al-Tamimi, Manoj K. Tewari, Manjul Tripathi, Simon Thomson, Edoardo Viaroli, Antonio Belli, Andrew T. King, Adel E. Helmy, Ivan S. Timofeev, Sarah Pyne,Dhaval P. Shukla, Dhananjaya I. Bhat, Andrew R. Maas, Franco Servadei, Geoffrey T. Manley,Garry Barton, Carole Turner, David K. Menon, Barbara Gregson, and Angelos G. Kolias,
23 April 2023
A new trial has found – where possible – surgeons should replace the removed section of the skull following surgery to treat a form of brain bleed. Researchers say the approach will save patients undergoing skull reconstruction further down the line. Read the full story.View publication
De-identified Bayesian personal identity matching for privacy-preserving record linkage despite errors: development and validation
Publication: BMC Medical Informatics and Decision Making
Cardinal RN, Moore A, Burchell M, Lewis JR
5 May 2023
Researchers developed a new way to link information between two organisations (e.g. an NHS organisation and a government education department) for research, without direct identifiers (such as names or dates of birth) being used during the linkage process itself.View publication
Risk factors for longer-term mortality in discharged patients with dementia and SARS-CoV-2 infection: a matched case–control study.
Publication: Journal of Alzheimer’s Disease
Chen S, Cardinal RN, Gräf S, O’Brien JT, Underwood BR
28 January 2023
We examined longer-term mortality in patients with dementia and SARS-CoV-2 infection. We found an increased mortality in patients with dementia beyond the acute phase of illness. We identified several investigation results associated with increased mortality, and increased mortality in patients prescribed antipsychotics or benzodiazepines.View publication
Publication: Frontiers in Psychiatry
Hannah LA, Walsh CM, Perez J, Jopling L, Cardinal RN, Cameron R
16 February 2023
Economic evidence for interventions in treatment-resistant depression is underdeveloped, particularly so for service-level interventions. Where evidence does exist, it is hampered by inconsistency in study design, methodological quality, and availability of high quality long-term outcomes evidence. This review identifies a number of key considerations and challenges for the design of future economic evaluations. Recommendations for research and suggestions for good practice are made.View publication
Maura Malpetti, Thomas E. Cope, Duncan Street, P. Simon Jones, Frank H. Hezemans, Elijah Mak, Kamen A. Tsvetanov, Timothy Rittman, W. Richard Bevan-Jones, Karalyn Patterson, Luca Passamonti, Tim D. Fryer, Young T. Hong, Franklin I. Aigbirhio, John T. O’Brien and James B. Rowe
08 March 2023
Brain scans like PET enable the visualisation and quantification of brain inflammation, which is an important and common pathological feature in dementia. Using PET we found that high levels of inflammation in frontal brain regions in people with frontotemporal dementia is associated with faster decline in their thinking performance over time. Our results highlight the potential for immunomodulatory treatment strategies in frontotemporal dementia.View publication
Using machine learning to model older adult inpatient trajectories from electronic health records data
Maria Herrero-Zazo, Tomas Fitzgerald, Vince Taylor, Helen Street, Afzal N. Chaudhry, John R. Bradley, Ewan Birney, Victoria L. Keevil
20 January 2023
- Time-series blood test & vital sign data from older inpatients were presented to HMM (Hidden Markov Models)
- Hidden clinically interpretable states were extracted, linked with diagnoses and death
- States modeled inpatient trajectories, differentiating risk from admission-discharge
- The clinical interpretation of HMM states helped explain how ML models organise data
Publication: Nature Nanotechnology
Filip Bošković, Jinbo Zhu, Ran Tivony, Alexander Ohmann, Kaikai Chen, Mohammed F. Alawami, Milan Đorđević, Niklas Ermann, Joana Pereira Dias, Michael Fairhead, Mark Howarth, Stephen Baker, Ulrich F. Keyser
16 January 2023
Respiratory infections are the major cause of death from infectious disease worldwide. Multiplexed diagnostic approaches are essential as many respiratory viruses have indistinguishable symptoms.
We created self-assembled DNA nanobait that can simultaneously identify multiple short RNA targets. The nanobait approach relies on specific target selection via toehold-mediated strand displacement and rapid read-out via nanopore sensing. Here, we show this platform can concurrently identify several common respiratory viruses, detecting a panel of short targets of viral nucleic acids from multiple viruses.
Our nanobait can be easily reprogrammed to discriminate viral variants, as we demonstrated for several key SARS-CoV-2 variants with single-nucleotide resolution. Lastly, we show that nanobait discriminates
between samples extracted from oropharyngeal swabs from negative and positive SARS-CoV-2 patients
Our system allows for multiplexed identification of native RNA molecules, providing a new scalable approach for diagnostics of multiple respiratory viruses in a single assay.View publication
Fully automated closed-loop insulin delivery in adults with type 2 diabetes: an open-label, single-center, randomized crossover trial
Publication: Nature Medicine
Aideen B. Daly, Charlotte K. Boughton, Munachiso Nwokolo, Sara Hartnell, Malgorzata E. Wilinska, Alina Cezar, Mark L. Evans & Roman Hovorka
12 January 2023
Cambridge scientists have successfully trialled an artificial pancreas for use by patients living with type 2 diabetes. The device – powered by an algorithm developed at the University of Cambridge – doubled the amount of time patients were in the target range for glucose and halved the time spent experiencing high glucose levels. Read the full news story.View publication
Longitudinal effect of clozapine-associated sedation on motivation in schizophrenia: naturalistic longitudinal study
Publication: British Journal of Psychiatry
Noham Wolpe, Shanquan Chen, Brian Kirkpatrick, Peter B. Jones, Christopher Jenkins, Rudolf N. Cardinal and Emilio Fernandez-Egea
10 January 2023
In a cohort of 187 people with schizophrenia treated with clozapine, we examined the relationship between clozapine, sedation, and aspects of symptoms: motivation/pleasure, and emotional expressivity. Clozapine was associated with increased sedation (a known side effect), and this sedation worsened motivation/pleasure; however, there was also a separate effect through which clozapine was directly associated with improved motivation/pleasure. These results highlight the important of addressing sedative side-effects of antipsychotic medications to improve quality of life.
Association between antidementia medication use and mortality in people diagnosed with dementia with Lewy bodies in the UK: a retrospective cohort study.
Publication: PLoS Medicine
Shanquan Chen, Annabel C Price, Rudolf N Cardinal, Sinéad Moylett, Anne D Kershenbaum, James Fitzgerald, Christoph Mueller, Robert Stewart, John T O’Brien
6 December 2022
In an observational study of people who had dementia with Lewy bodies, use of cholinesterase inhibitors (a symptomatic treatment) was associated with shorter duration of hospital admissions and decreased risk of mortality.View publication
Factors Associated with Significant Weight Loss in Hospitalised Patients with COVID-19: A Retrospective Cohort Study in a Large Teaching Hospital
Dimitra Zannidi, Pinal S. Patel, Eleni Leventea, Jessica Paciepnik, Frances Dobson, Caroline Heyes, Robert J. B. Goudie, Linda M. Oude Griep, Jacobus Preller, and Lynsey N. Spillman,
8 October 2022
Previous research has shown that people hospitalised with COVID-19 are at risk of weight loss and malnutrition. This study looked at patients who experienced weight loss of 10% or more during their hospital admission to Cambridge University Hospitals NHS with COVID-19 during the first wave of the pandemic. Weight loss of 10% or more is considered a large amount to lose as it increases the chance of someone becoming more poorly and not surviving. Therefore, preventing weight loss may help patients to survive and recover. The study looked at risk factors for weight loss to help better recognise the patients that need more support to prevent weight loss.View publication
Publication: European Heart Journal
Paddy C Dempsey, Alex V Rowlands, Tessa Strain, Francesco Zaccardi, Nathan Dawkins, Cameron Razieh, Melanie J Davies, Kamlesh K Khunti, Charlotte L Edwardson, Katrien Wijndaele, Soren Brage, Tom Yates
27 October 2022
Increasing physical activity of any intensity is beneficial for health, but new research published in the European Heart Journal shows that there is a greater reduction in cardiovascular disease risk when more of that activity is of at least moderate intensity.View publication
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
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.View publication
Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay
Publication: Endocrine Connections
Martin Wiegand, David J Halsall, Sarah L Cowan, Kevin Taylor, Robert J B Goudie, Jacobus Preller, Mark Gurnell
26 August 2022
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.View publication
The prognostic and discriminatory utility of the Clinical Frailty Scale and modified frailty Index compared to age
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
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.View publication
Widespread cell stress and mitochondrial dysfunction occur in patients with early Alzheimer’s disease
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
Researchers explored whether widespread cell stress and mitochondrial dysfunction occur in patients with early Alzheimer’s DiseaseView publication
Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells
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
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.View publication
Evaluation of Dynamic Contrast-Enhanced MRI Measures of Lung Congestion and Endothelial Permeability in Heart Failure: A Prospective Method Validation Study
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
Lung congestion is common in patients with heart failure. Enhanced MRI may be appropriate method for accurate measurement of lung fluid.View publication