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1. Projective rigidity of point-line configurations in the plane

Author

Berman, Leah, Lundqvist, Signe, Schulze, Bernd, Servatius, Brigitte, Servatius, Herman, Stokes, Klara, and Whiteley, Walter

Subjects
Mathematics - Metric Geometry, Mathematics - Algebraic Geometry, Mathematics - Combinatorics, Mathematics - Differential Geometry, Mathematics - Group Theory
Abstract

In this paper, we establish a general setup for studying incidence-preserving motions of projective geometric configurations of points and lines via a "projective rigidity matrix". The spaces of infinitesimal motions of a point-line configuration and dependencies amongst the point-line incidences can be interpreted as the kernel and co-kernel of this projective rigidity matrix, respectively. We also introduce a symmetry-adapted projective rigidity matrix for analysing symmetric configurations and their symmetry-preserving motions. The symmetry may be a point group or a more general symmetry, such as an autopolarity.

Published
2024

2. Bridging the Gap Between Physical Health and Autism Spectrum Disorder

Author

Sala R, Amet L, Blagojevic-Stokic N, Shattock P, and Whiteley P

Subjects
autism spectrum disorder (asd), physical health, comorbidity, inequality, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Regina Sala,1 Lorene Amet,2 Natasa Blagojevic-Stokic,3 Paul Shattock,4 Paul Whiteley5 1Centre for Psychiatry, Wolfson Institute, Barts & The London School of Medicine & Dentistry Queen Mary University of London, London, UK; 2Autism Treatment Plus, Edinburgh, UK; 3Thinking Autism, London, UK; 4Education & Services for People with Autism, Sunderland, UK; 5Education & Services for People with Autism Research, Sunderland, UKCorrespondence: Dr Regina SalaCentre for Psychiatry, Wolfson Institute, Barts & The London School of Medicine & Dentistry Queen Mary University of London, London, UKEmail regina.sala@nhs.netAbstract: Autism spectrum disorder (ASD) is a highly complex and heterogeneous developmental disorder that affects how individuals communicate with other people and relate to the world around them. Research and clinical focus on the behavioural and cognitive manifestations of ASD, whilst important, have obscured the recognition that ASD is also commonly associated with a range of physical and mental health conditions. Many physical conditions appear with greater frequency in individuals with ASD compared to non-ASD populations. These can contribute to a worsening of social communication and behaviour, lower quality of life, higher morbidity and premature mortality. We highlight some of the key physical comorbidities affecting the immune and the gastrointestinal systems, metabolism and brain function in ASD. We discuss how healthcare professionals working with individuals with ASD and parents/carers have a duty to recognise their needs in order to improve their overall health and wellbeing, deliver equality in their healthcare experiences and reduce the likelihood of morbidity and early mortality associated with the condition.Keywords: autism spectrum disorder, ASD, physical health, comorbidity, inequality

Published
2020

3. Is Autism Inborn And Lifelong For Everyone?

Author

Whiteley P, Carr K, and Shattock P

Subjects
autism, regression, innate, lifelong, acquired, heterogeneity, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Paul Whiteley, Kevin Carr, Paul Shattock ESPA Research, Sunderland, UKCorrespondence: Paul WhiteleyThe Robert Luff Laboratory, Unit 133i Business Innovation Centre (BIC), ESPA Research, Wearfield, Sunderland SR5 2TA, UKTel +44 191 516 6366Email paul.whiteley@espa-research.org.ukAbstract: Autism or autism spectrum disorder (ASD) is described as a lifelong condition with core behavioural symptoms appearing during infancy or early childhood. Genetic and other effects occurring during the earliest times of life are thought to play a significant contributory role to the presentation of autism, denoting that autism is typically seen as an innate or inborn condition. Such descriptions have, and continue to, define autism research and clinical practice. Inspection of the existing research literature, however, suggests that within the vast heterogeneity of autism, not everyone experiences autism in such a prescribed way. Various reports have observed the presentation of “acquired autism” following a period of typical development. Other findings have documented an abatement of clinically relevant autistic features and related comorbid pathology for some. Such reports offer important insights into the heterogeneity and complexity of autism.Keywords: autism, regression, innate, lifelong, acquired, heterogeneity

Published
2019

8. The piranha gut microbiome provides a selective lens into river water biodiversity

Author

Sheila da Silva, Paton Vuong, João Ricardo Vidal Amaral, Vicente Almeida Serafim da Silva, Selma Soares de Oliveira, Alane Beatriz Vermelho, David John Beale, Andrew Bissett, Andrew Steven Whiteley, Parwinder Kaur, and Andrew Macrae

Subjects
Metagenomics, Serrasalmus rhombeus, Host-associated microbiome, Amazon river microbiome, Biotechnology, Medicine, Science
Abstract

Abstract Advances in omics technologies have enabled the in-depth study of microbial communities and their metabolic profiles from all environments. Here metagenomes were sampled from piranha (Serrasalmus rhombeus) and from river water from the Rio São Benedito (Amazon Basin). Shotgun metagenome sequencing was used to explore diversity and to test whether fish microbiomes are a good proxy for river microbiome studies. The results showed that the fish microbiomes were not significantly different from the river water microbiomes at higher taxonomic ranks. However, at the genus level, fish microbiome alpha diversity decreased, and beta diversity increased. This result repeated for functional gene abundances associated with specific metabolic categories (SEED level 3). A clear delineation between water and fish was seen for beta diversity. The piranha microbiome provides a good and representative subset of its river water microbiome. Variations seen in beta biodiversity were expected and can be explained by temporal variations in the fish microbiome in response to stronger selective forces on its biodiversity. Metagenome assembled genomes construction was better from the fish samples. This study has revealed that the microbiome of a piranha tells us a lot about its river water microbiome and function.

Published
2024
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9. A qualitative study identifying implementation strategies using the i-PARIHS framework to increase access to pre-exposure prophylaxis at federally qualified health centers in Mississippi

Author

Trisha Arnold, Laura Whiteley, Kayla K. Giorlando, Andrew P. Barnett, Ariana M. Albanese, Avery Leigland, Courtney Sims-Gomillia, A. Rani Elwy, Precious Patrick Edet, Demetra M. Lewis, James B. Brock, and Larry K. Brown

Subjects
HIV Prevention, Implementation Science, Pre-exposure prophylaxis (PrEP), Telemedicine, Medicine (General), R5-920
Abstract

Abstract Background Mississippi (MS) experiences disproportionally high rates of new HIV infections and limited availability of pre-exposure prophylaxis (PrEP). Federally Qualified Health Centers (FQHCs) are poised to increase access to PrEP. However, little is known about the implementation strategies needed to successfully integrate PrEP services into FQHCs in MS. Purpose The study had two objectives: identify barriers and facilitators to PrEP use and to develop tailored implementation strategies for FQHCs. Methods Semi-structured interviews were conducted with 19 staff and 17 PrEP-eligible patients in MS FQHCs between April 2021 and March 2022. The interview was guided by the integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework which covered PrEP facilitators and barriers. Interviews were coded according to the i-PARIHS domains of context, innovation, and recipients, followed by thematic analysis of these codes. Identified implementation strategies were presented to 9 FQHC staff for feedback. Results Data suggested that PrEP use at FQHCs is influenced by patient and clinic staff knowledge with higher levels of knowledge reflecting more PrEP use. Perceived side effects are the most significant barrier to PrEP use for patients, but participants also identified several other barriers including low HIV risk perception and untrained providers. Despite these barriers, patients also expressed a strong motivation to protect themselves, their partners, and their communities from HIV. Implementation strategies included education and provider training which were perceived as acceptable and appropriate. Conclusions Though patients are motivated to increase protection against HIV, multiple barriers threaten uptake of PrEP within FQHCs in MS. Educating patients and providers, as well as training providers, are promising implementation strategies to overcome these barriers.

Published
2024
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10. Cohort study of cardiovascular safety of different COVID-19 vaccination doses among 46 million adults in England

Author

Samantha Ip, Teri-Louise North, Fatemeh Torabi, Yangfan Li, Hoda Abbasizanjani, Ashley Akbari, Elsie Horne, Rachel Denholm, Spencer Keene, Spiros Denaxas, Amitava Banerjee, Kamlesh Khunti, Cathie Sudlow, William N. Whiteley, Jonathan A. C. Sterne, Angela M. Wood, Venexia Walker, the CVD-COVID-UK/COVID-IMPACT Consortium, and the Longitudinal Health and Wellbeing COVID-19 National Core Study

Subjects
Science
Abstract

Abstract The first dose of COVID-19 vaccines led to an overall reduction in cardiovascular events, and in rare cases, cardiovascular complications. There is less information about the effect of second and booster doses on cardiovascular diseases. Using longitudinal health records from 45.7 million adults in England between December 2020 and January 2022, our study compared the incidence of thrombotic and cardiovascular complications up to 26 weeks after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA-1273). These findings support the wide uptake of future COVID-19 vaccination programs.

Published
2024
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11. Intensity Profile Projection: A Framework for Continuous-Time Representation Learning for Dynamic Networks

Author

Modell, Alexander, Gallagher, Ian, Ceccherini, Emma, Whiteley, Nick, and Rubin-Delanchy, Patrick

Subjects
Computer Science - Machine Learning, Statistics - Methodology, Statistics - Machine Learning, 62H12 (primary), 62H30 (secondary)
Abstract

We present a new representation learning framework, Intensity Profile Projection, for continuous-time dynamic network data. Given triples $(i,j,t)$, each representing a time-stamped ($t$) interaction between two entities ($i,j$), our procedure returns a continuous-time trajectory for each node, representing its behaviour over time. The framework consists of three stages: estimating pairwise intensity functions, e.g. via kernel smoothing; learning a projection which minimises a notion of intensity reconstruction error; and constructing evolving node representations via the learned projection. The trajectories satisfy two properties, known as structural and temporal coherence, which we see as fundamental for reliable inference. Moreoever, we develop estimation theory providing tight control on the error of any estimated trajectory, indicating that the representations could even be used in quite noise-sensitive follow-on analyses. The theory also elucidates the role of smoothing as a bias-variance trade-off, and shows how we can reduce the level of smoothing as the signal-to-noise ratio increases on account of the algorithm `borrowing strength' across the network., Comment: 38 pages, 10 figures

Published
2023

12. Hierarchical clustering with dot products recovers hidden tree structure

Author

Gray, Annie, Modell, Alexander, Rubin-Delanchy, Patrick, and Whiteley, Nick

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning
Abstract

In this paper we offer a new perspective on the well established agglomerative clustering algorithm, focusing on recovery of hierarchical structure. We recommend a simple variant of the standard algorithm, in which clusters are merged by maximum average dot product and not, for example, by minimum distance or within-cluster variance. We demonstrate that the tree output by this algorithm provides a bona fide estimate of generative hierarchical structure in data, under a generic probabilistic graphical model. The key technical innovations are to understand how hierarchical information in this model translates into tree geometry which can be recovered from data, and to characterise the benefits of simultaneously growing sample size and data dimension. We demonstrate superior tree recovery performance with real data over existing approaches such as UPGMA, Ward's method, and HDBSCAN.

Published
2023

18. Impact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study

Author

Cezard, Genevieve I., Denholm, Rachel E., Knight, Rochelle, Wei, Yinghui, Teece, Lucy, Toms, Renin, Forbes, Harriet J., Walker, Alex J., Fisher, Louis, Massey, Jon, Hopcroft, Lisa E. M., Horne, Elsie M. F., Taylor, Kurt, Palmer, Tom, Arab, Marwa Al, Cuitun Coronado, Jose Ignacio, Ip, Samantha H. Y., Davy, Simon, Dillingham, Iain, Bacon, Sebastian, Mehrkar, Amir, Morton, Caroline E., Greaves, Felix, Hyams, Catherine, Davey Smith, George, Macleod, John, Chaturvedi, Nishi, Goldacre, Ben, Whiteley, William N., Wood, Angela M., Sterne, Jonathan A. C., and Walker, Venexia

Published
2024
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21. Patient Preferences for Treatment in Relapsed/Refractory Acute Leukemia in the United Kingdom: A Discrete Choice Experiment

Author

Mott DJ, Hitch J, Nier S, Pemberton-Whiteley Z, and Skedgel C

Subjects
acute leukemia, hematology, oncology, patient preferences, discrete choice experiment, Medicine (General), R5-920
Abstract

David John Mott,1 Jake Hitch,1,2 Samantha Nier,3 Zack Pemberton-Whiteley,3,4 Chris Skedgel1 1Office of Health Economics, London, UK; 2Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK; 3Acute Leukemia Advocates Network, Bern, Switzerland; 4Leukemia Care, Worcester, UKCorrespondence: David John Mott, Email dmott@ohe.orgBackground: Acute leukemia is a cancer of the white blood cells which progresses rapidly and aggressively. There are two types: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The latter has a rare subtype: acute promyelocytic leukemia (APL). For some patients, following first-line treatment, remission is not achieved (“refractory disease”), and for others the leukemia returns after achieving remission (“relapse”). For these individuals, outcomes are typically poor. It is, therefore, important to understand patients’ treatment priorities in this context.Methods: Building upon formative qualitative research, an online survey containing a discrete choice experiment (DCE) was designed to explore patients’ treatment preferences in the relapsed/refractory setting. The DCE attributes were mode of administration; quality of life during treatment; chance of response; duration of response; and quality of life during response. Each respondent completed twelve scenarios containing two hypothetical treatments. Participants were eligible if they lived in the United Kingdom and had a diagnosis of acute leukemia. The data were analysed using a latent class model.Results: A total of 95 patients completed the survey. The latent class analysis identified two classes. For both, chance of response was the most important attribute. For class 1, every attribute was important, whereas for class 2, the only important attributes were quality of life (during treatment and response) and chance of response. A greater proportion of respondents would fall into class 1 overall, and those with ALL or APL and those more recently diagnosed were more likely to be in class 2.Conclusion: Our results indicate that patients are strongly concerned about the chance of response, as well as quality of life (to a lesser extent), when faced with different treatment options in the relapsed/refractory setting. However, there is significant preference heterogeneity within the patient population, and other treatment characteristics also matter to many.Keywords: acute leukemia, hematology, oncology, patient preferences, discrete choice experiment

Published
2024

22. The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses

Author

Rosie M. Walker, Michael Chong, Nicolas Perrot, Marie Pigeyre, Danni A. Gadd, Aleks Stolicyn, Liu Shi, Archie Campbell, Xueyi Shen, Heather C. Whalley, Alejo Nevado-Holgado, Andrew M. McIntosh, Stefan Heitmeier, Sumathy Rangarajan, Martin O’Donnell, Eric E. Smith, Salim Yusuf, William N. Whiteley, and Guillaume Paré

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Decline in cognitive function is the most feared aspect of ageing. Poorer midlife cognitive function is associated with increased dementia and stroke risk. The mechanisms underlying variation in cognitive function are uncertain. Here, we assessed associations between 1160 proteins’ plasma levels and two measures of cognitive function, the digit symbol substitution test (DSST) and the Montreal Cognitive Assessment in 1198 PURE-MIND participants. We identified five DSST performance-associated proteins (NCAN, BCAN, CA14, MOG, CDCP1), with NCAN and CDCP1 showing replicated association in an independent cohort, GS (N = 1053). MRI-assessed structural brain phenotypes partially mediated (8–19%) associations between NCAN, BCAN, and MOG, and DSST performance. Mendelian randomisation analyses suggested higher CA14 levels might cause larger hippocampal volume and increased stroke risk, whilst higher CDCP1 levels might increase intracranial aneurysm risk. Our findings highlight candidates for further study and the potential for drug repurposing to reduce the risk of stroke and cognitive decline.

Published
2024
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23. Systematic review on techniques for the creation of pneumoperitoneum in laparoscopic surgeries

Author

Asna Zehra Naqvi, Vignesh Balasubaramaniam, Wasif Raza, Lajpat Rai, and Graham S Whiteley

Subjects
veress needle, hasson technique, open technique, closed technique, laparoscopic surgery, Medicine
Abstract

Recently, laparoscopic surgeries (LPSs) are becoming increasingly prevalent. Incorporating these methods into clinical practice necessitates an in-depth understanding of the surgical techniques and multifaceted instrumentation that are specific to a slightly invasive operation. Within this systematic review, attention is directed to the technique for pneumoperitoneum creation, like the open and closed technique, to select optimal procedures along with appropriate utilization, with prominence on complication avoidance. This systematic literature review (SLR) examined significant findings from 2018 to 2023. This SLR complies with the quality standards suggested by the PRISMA document. Web of Science, SCOPUS, ProQuest, ScienceDirect, and SpringerLink are the resources. The exclusion criteria included case reports, abstracts, and letters, as well as inclusion criteria included randomized, quasi-randomized, non-randomized, and cohort investigations on human patients, provided that they liked access safety methods and presented values. According to the findings, it can be concluded that the LP inspection of the abdominal cavity (AC), which necessitates cannula implantation, is safe and effective. Closed (Veress needle technique) and open (Hasson technique) pneumoperitoneum induction techniques are frequently utilized. Most laparoscopy (LP) surgeons prefer closed LP utilizing a Veress needle and the first trocar’s masked insertion. Critics of the Veress needle, however, assert that this technique increases the risk of vascular injury. According to proponents of the open Hasson technique, vascular injury could be entirely avoided. The use of an open approach utilizing a blunt-tipped trocar for the formation of pneumoperitoneum may provide a potentially safer alternative during LPSs, depending on safety considerations.

Published
2024
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25. DIRECT, a low-cost system for high-speed, low-noise imaging of fluorescent biological samples

Author

Whiteley, Isabell, Song, Chenchen, Howe, Glenn A, Knöpfel, Thomas, and Rowlands, Christopher J

Subjects
Physics - Optics
Abstract

A targeted imaging system has been developed for applications requiring recording from stationary samples at high spatiotemporal resolutions. It works by illuminating regions of interest in rapid sequence, and recording the signal from the whole field of view onto a single photodetector, and can be implemented at low cost on an existing microscope without compromising existing functionality. The system is characterized in terms of speed, spatial resolution, and tissue penetration depth, before being used to record individual action potentials from ASAP-3 expressing neurons in an ex vivo mouse brain slice preparation., Comment: 17 pages, 8 figures

Published
2022

26. Implications of sparsity and high triangle density for graph representation learning

Author

Sansford, Hannah, Modell, Alexander, Whiteley, Nick, and Rubin-Delanchy, Patrick

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning
Abstract

Recent work has shown that sparse graphs containing many triangles cannot be reproduced using a finite-dimensional representation of the nodes, in which link probabilities are inner products. Here, we show that such graphs can be reproduced using an infinite-dimensional inner product model, where the node representations lie on a low-dimensional manifold. Recovering a global representation of the manifold is impossible in a sparse regime. However, we can zoom in on local neighbourhoods, where a lower-dimensional representation is possible. As our constructions allow the points to be uniformly distributed on the manifold, we find evidence against the common perception that triangles imply community structure.

Published
2022

27. Clinical decision support to Optimize Care of patients with Atrial Fibrillation or flutter in the Emergency department: protocol of a stepped-wedge cluster randomized pragmatic trial (O’CAFÉ trial)

Author

Vinson, David R, Rauchwerger, Adina S, Karadi, Chandu A, Shan, Judy, Warton, E Margaret, Zhang, Jennifer Y, Ballard, Dustin W, Mark, Dustin G, Hofmann, Erik R, Cotton, Dale M, Durant, Edward J, Lin, James S, Sax, Dana R, Poth, Luke S, Gamboa, Stephen H, Ghiya, Meena S, Kene, Mamata V, Ganapathy, Anuradha, Whiteley, Patrick M, Bouvet, Sean C, Babakhanian, Leon, Kwok, Edward W, Solomon, Matthew D, Go, Alan S, and Reed, Mary E

Subjects
Health Services and Systems, Health Sciences, Clinical Research, Clinical Trials and Supportive Activities, Comparative Effectiveness Research, Heart Disease, Health Services, Emergency Care, Prevention, Cardiovascular, 7.3 Management and decision making, Management of diseases and conditions, Stroke, Good Health and Well Being, Adult, Humans, Anticoagulants, Atrial Fibrillation, Atrial Flutter, Decision Support Systems, Clinical, Emergency Service, Hospital, Randomized Controlled Trials as Topic, Pragmatic Clinical Trials as Topic, Atrial fibrillation, Atrial flutter, Emergency medicine, Randomized trial, Cardioversion, Patient admission, Kaiser Permanente CREST Network, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology, General & Internal Medicine, Clinical sciences, Epidemiology, Health services and systems
Abstract

BackgroundManagement of adults with atrial fibrillation (AF) or atrial flutter in the emergency department (ED) includes rate reduction, cardioversion, and stroke prevention. Different approaches to these components of care may lead to variation in frequency of hospitalization and stroke prevention actions, with significant implications for patient experience, cost of care, and risk of complications. Standardization using evidence-based recommendations could reduce variation in management, preventable hospitalizations, and stroke risk.MethodsWe describe the rationale for our ED-based AF treatment recommendations. We also describe the development of an electronic clinical decision support system (CDSS) to deliver these recommendations to emergency physicians at the point of care. We implemented the CDSS at three pilot sites to assess feasibility and solicit user feedback. We will evaluate the impact of the CDSS on hospitalization and stroke prevention actions using a stepped-wedge cluster randomized pragmatic clinical trial across 13 community EDs in Northern California.DiscussionWe hypothesize that the CDSS intervention will reduce hospitalization of adults with isolated AF or atrial flutter presenting to the ED and increase anticoagulation prescription in eligible patients at the time of ED discharge and within 30 days. If our hypotheses are confirmed, the treatment protocol and CDSS could be recommended to other EDs to improve management of adults with AF or atrial flutter.Trial registrationClinicalTrials.gov NCT05009225 .  Registered on 17 August 2021.

Published
2023

28. Full-permutation dynamical decoupling in triple-quantum-dot spin qubits

Author

Sun, Bo, Brecht, Teresa, Fong, Bryan, Akmal, Moonmoon, Blumoff, Jacob Z., Cain, Tyler A., Carter, Faustin W., Finestone, Dylan H., Fireman, Micha N., Ha, Wonill, Hatke, Anthony T., Hickey, Ryan M., Jackson, Clayton A. C., Jenkins, Ian, Jones, Aaron M., Pan, Andrew, Ward, Daniel R., Weinstein, Aaron J., Whiteley, Samuel J., Williams, Parker, Borselli, Matthew G., Rakher, Matthew T., and Ladd, Thaddeus D.

Subjects
Quantum Physics
Abstract

Dynamical decoupling of spin qubits in silicon can enhance fidelity and be used to extract the frequency spectra of noise processes. We demonstrate a full-permutation dynamical decoupling technique that cyclically exchanges the spins in a triple-dot qubit. This sequence not only suppresses both low frequency charge-noise- and magnetic-noise-induced errors; it also refocuses leakage errors to first order, which is particularly interesting for encoded exchange-only qubits. For a specific construction, which we call NZ1y, the qubit is isolated from error sources to such a degree that we measure a remarkable exchange pulse error of $5\times10^{-5}$. This sequence maintains a quantum state for roughly 18,000 exchange pulses, extending the qubit coherence from $T_2^*=2~\mu$s to $T_2 = 720~\mu$s. We experimentally validate an error model that includes $1/f$ charge noise and $1/f$ magnetic noise in two ways: by direct exchange-qubit simulation, and by integration of the assumed noise spectra with derived filter functions, both of which reproduce the measured error and leakage with respect to changing the repetition rate., Comment: 12 pages, 4 figures

Published
2022

29. Statistical exploration of the Manifold Hypothesis

Author

Whiteley, Nick, Gray, Annie, and Rubin-Delanchy, Patrick

Subjects
Statistics - Methodology, Computer Science - Machine Learning, Statistics - Machine Learning, 62R20, 62R40, 62G05, 62G20, 62R07, 62-08, 62H25, 62H30
Abstract

The Manifold Hypothesis is a widely accepted tenet of Machine Learning which asserts that nominally high-dimensional data are in fact concentrated near a low-dimensional manifold, embedded in high-dimensional space. This phenomenon is observed empirically in many real world situations, has led to development of a wide range of statistical methods in the last few decades, and has been suggested as a key factor in the success of modern AI technologies. We show that rich and sometimes intricate manifold structure in data can emerge from a generic and remarkably simple statistical model -- the Latent Metric Model -- via elementary concepts such as latent variables, correlation and stationarity. This establishes a general statistical explanation for why the Manifold Hypothesis seems to hold in so many situations. Informed by the Latent Metric Model we derive procedures to discover and interpret the geometry of high-dimensional data, and explore hypotheses about the data generating mechanism. These procedures operate under minimal assumptions and make use of well known, scaleable graph-analytic algorithms.

Published
2022

32. Impact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study

Author

Genevieve I. Cezard, Rachel E. Denholm, Rochelle Knight, Yinghui Wei, Lucy Teece, Renin Toms, Harriet J. Forbes, Alex J. Walker, Louis Fisher, Jon Massey, Lisa E. M. Hopcroft, Elsie M. F. Horne, Kurt Taylor, Tom Palmer, Marwa Al Arab, Jose Ignacio Cuitun Coronado, Samantha H. Y. Ip, Simon Davy, Iain Dillingham, Sebastian Bacon, Amir Mehrkar, Caroline E. Morton, Felix Greaves, Catherine Hyams, George Davey Smith, John Macleod, Nishi Chaturvedi, Ben Goldacre, William N. Whiteley, Angela M. Wood, Jonathan A. C. Sterne, Venexia Walker, and On behalf of the Longitudinal Health and Wellbeing and Data and Connectivity UK COVID-19 National Core Studies, CONVALESCENCE study and the OpenSAFELY collaborative

Subjects
Science
Abstract

Abstract Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a ‘pre-vaccination’ cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and ‘vaccinated’ and ‘unvaccinated’ cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years.

Published
2024
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33. A comprehensive analysis of APOE genotype effects on human brain structure in the UK Biobank

Author

Verena Heise, Alison Offer, William Whiteley, Clare E. Mackay, Jane M. Armitage, and Sarah Parish

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Alzheimer’s disease (AD) risk is increased in carriers of the apolipoprotein E (APOE) ε4 allele and decreased in ε2 allele carriers compared with the ε3ε3 genotype. The aim of this study was to determine whether: the APOE genotype affects brain grey (GM) or white matter (WM) structure; and if differences exist, the age when they become apparent and whether there are differential effects by sex. We used cross-sectional magnetic resonance imaging data from ~43,000 (28,494 after pre-processing) white British cognitively healthy participants (7,446 APOE ε4 carriers) aged 45–80 years from the UK Biobank cohort and investigated image-derived phenotypes (IDPs). We observed no statistically significant effects of APOE genotype on GM structure volumes or median T2* in subcortical structures, a measure related to iron content. The volume of white matter hyperintensities differed significantly between APOE genotype groups with higher volumes in APOE ε4ε4 (effect size 0.14 standard deviations [SD]) and ε3ε4 carriers (effect size 0.04 SD) but no differences in ε2 carriers compared with ε3ε3 carriers. WM integrity measures in the dorsal (mean diffusivity [MD]) and ventral cingulum (MD and intracellular volume fraction), posterior thalamic radiation (MD and isotropic volume fraction) and sagittal stratum (MD) indicated lower integrity in APOE ε4ε4 carriers (effect sizes around 0.2–0.3 SD) and ε3ε4 (effect sizes around 0.05 SD) carriers but no differences in ε2 carriers compared with the APOE ε3ε3 genotype. Effects did not differ between men and women. APOE ε4 homozygotes had lower WM integrity specifically at older ages with a steeper decline of WM integrity from the age of 60 that corresponds to around 5 years greater “brain age”. APOE genotype affects various white matters measures, which might be indicative of preclinical AD processes. This hypothesis can be assessed in future when clinical outcomes become available.

Published
2024
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34. Consistent and fast inference in compartmental models of epidemics using Poisson Approximate Likelihoods

Author

Whitehouse, Michael, Whiteley, Nick, and Rimella, Lorenzo

Subjects
Statistics - Methodology, Computer Science - Machine Learning
Abstract

Addressing the challenge of scaling-up epidemiological inference to complex and heterogeneous models, we introduce Poisson Approximate Likelihood (PAL) methods. In contrast to the popular ODE approach to compartmental modelling, in which a large population limit is used to motivate a deterministic model, PALs are derived from approximate filtering equations for finite-population, stochastic compartmental models, and the large population limit drives consistency of maximum PAL estimators. Our theoretical results appear to be the first likelihood-based parameter estimation consistency results which apply to a broad class of partially observed stochastic compartmental models and address the large population limit. PALs are simple to implement, involving only elementary arithmetic operations and no tuning parameters, and fast to evaluate, requiring no simulation from the model and having computational cost independent of population size. Through examples we demonstrate how PALs can be used to: fit an age-structured model of influenza, taking advantage of automatic differentiation in Stan; compare over-dispersion mechanisms in a model of rotavirus by embedding PALs within sequential Monte Carlo; and evaluate the role of unit-specific parameters in a meta-population model of measles.

Published
2022

35. Ontology-Driven and Weakly Supervised Rare Disease Identification from Clinical Notes

Author

Dong, Hang, Suárez-Paniagua, Víctor, Zhang, Huayu, Wang, Minhong, Casey, Arlene, Davidson, Emma, Chen, Jiaoyan, Alex, Beatrice, Whiteley, William, and Wu, Honghan

Subjects
Computer Science - Computation and Language, 68T50 (Primary), 68T30 (Secondary), I.2.7, J.3
Abstract

Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts. We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-based framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations. The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes). We discuss the usefulness of the weak supervision approach and propose directions for future studies., Comment: Accepted for BMC Medical Informatics and Decision Making, structured abstract in full text, 16 pages, 4 figures (and extra 7 pages, 1 figure in the supplementary material)

Published
2022
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36. The evolving value assessment of cancer therapies: Results from a modified Delphi study

Author

Myrto Lee, Hugo Larose, Martin Gräbeldinger, Jon Williams, Anne-Marie Baird, Susan Brown, Johannes Bruns, Russell Clark, Javier Cortes, Giuseppe Curigliano, Andrea Ferris, Louis P. Garrison, Y.K. Gupta, Ravindran Kanesvaran, Gary Lyman, Luca Pani, Zack Pemberton-Whiteley, Tomas Salmonson, Peter Sawicki, Barry Stein, Dong-Churl Suh, Galina Velikova, and Jens Grueger

Subjects
Public aspects of medicine, RA1-1270
Abstract

The move toward early detection and treatment of cancer presents challenges for value assessment using traditional endpoints. Current cancer management rarely considers the full economic and societal benefits of therapies. Our study used a modified Delphi process to develop principles for defining and assessing value of cancer therapies that aligns with the current trajectory of oncology research and reflects broader notions of value. 24 experts participated in consensus-building activities across 5 months (16 took part in structured interactions, including a survey, plenary sessions, interviews, and off-line discussions, while 8 participated in interviews). Discussion focused on: 1) which oncology-relevant endpoints should be used for assessing treatments for early-stage cancer and access decisions for early-stage treatments, and 2) the importance of additional value components and how these can be integrated in value assessments. The expert group reached consensus on 4 principles in relation to the first area (consider oncology-relevant endpoints other than overall survival; build evidence for endpoints that provide earlier indication of efficacy; develop evidence for the next generation of predictive measures; use managed entry agreements supported by ongoing evidence collection to address decision-maker evidence needs) and 3 principles in relation to the second (routinely use patient reported outcomes in value assessments; assess broad economic impact of new medicines; consider other value aspects of relevance to patients and society).

Published
2024
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37. Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Author

Jannik Boos, Caspar I. van der Made, Gayatri Ramakrishnan, Eamon Coughlan, Rosanna Asselta, Britt-Sabina Löscher, Luca V.C. Valenti, Rafael de Cid, Luis Bujanda, Antonio Julià, Erola Pairo-Castineira, J. Kenneth Baillie, Sandra May, Berina Zametica, Julia Heggemann, Agustín Albillos, Jesus M. Banales, Jordi Barretina, Natalia Blay, Paolo Bonfanti, Maria Buti, Javier Fernandez, Sara Marsal, Daniele Prati, Luisa Ronzoni, Nicoletta Sacchi, Joachim L. Schultze, Olaf Riess, Andre Franke, Konrad Rawlik, David Ellinghaus, Alexander Hoischen, Axel Schmidt, Kerstin U. Ludwig, Valeria Rimoldi, Elvezia M. Paraboschi, Alessandra Bandera, Flora Peyvandi, Giacomo Grasselli, Francesco Blasi, Francesco Malvestiti, Serena Pelusi, Cristiana Bianco, Lorenzo Miano, Angela Lombardi, Pietro Invernizzi, Alessio Gerussi, Giuseppe Citerio, Andrea Biondi, Maria Grazia Valsecchi, Marina Elena Cazzaniga, Giuseppe Foti, Ilaria Beretta, Mariella D'Angiò, Laura Rachele Bettini, Xavier Farré, Susana Iraola-Guzmán, Manolis Kogevinas, Gemma Castaño-Vinyals, Koldo Garcia-Etxebarria, Beatriz Nafria, Mauro D'Amato, Adriana Palom, Colin Begg, Sara Clohisey, Charles Hinds, Peter Horby, Julian Knight, Lowell Ling, David Maslove, Danny McAuley, Johnny Millar, Hugh Montgomery, Alistair Nichol, Peter J.M. Openshaw, Alexandre C. Pereira, Chris P. Ponting, Kathy Rowan, Malcolm G. Semple, Manu Shankar-Hari, Charlotte Summers, Timothy Walsh, Latha Aravindan, Ruth Armstrong, Heather Biggs, Ceilia Boz, Adam Brown, Richard Clark, Audrey Coutts, Judy Coyle, Louise Cullum, Sukamal Das, Nicky Day, Lorna Donnelly, Esther Duncan, Angie Fawkes, Paul Fineran, Max Head Fourman, Anita Furlong, James Furniss, Bernadette Gallagher, Tammy Gilchrist, Ailsa Golightly, Fiona Griffiths, Katarzyna Hafezi, Debbie Hamilton, Ross Hendry, Andy Law, Dawn Law, Rachel Law, Sarah Law, Rebecca Lidstone-Scott, Louise Macgillivray, Alan Maclean, Hanning Mal, Sarah McCafferty, Ellie Mcmaster, Jen Meikle, Shona C. Moore, Kirstie Morrice, Lee Murphy, Sheena Murphy, Mybaya Hellen, Wilna Oosthuyzen, Chenqing Zheng, Jiantao Chen, Nick Parkinson, Trevor Paterson, Katherine Schon, Andrew Stenhouse, Mihaela Das, Maaike Swets, Helen Szoor-McElhinney, Filip Taneski, Lance Turtle, Tony Wackett, Mairi Ward, Jane Weaver, Nicola Wrobel, Marie Zechner, Gill Arbane, Aneta Bociek, Sara Campos, Neus Grau, Tim Owen Jones, Rosario Lim, Martina Marotti, Marlies Ostermann, Christopher Whitton, Zoe Alldis, Raine Astin-Chamberlain, Fatima Bibi, Jack Biddle, Sarah Blow, Matthew Bolton, Catherine Borra, Ruth Bowles, Maudrian Burton, Yasmin Choudhury, David Collier, Amber Cox, Amy Easthope, Patrizia Ebano, Stavros Fotiadis, Jana Gurasashvili, Rosslyn Halls, Pippa Hartridge, Delordson Kallon, Jamila Kassam, Ivone Lancoma-Malcolm, Maninderpal Matharu, Peter May, Oliver Mitchelmore, Tabitha Newman, Mital Patel, Jane Pheby, Irene Pinzuti, Zoe Prime, Oleksandra Prysyazhna, Julian Shiel, Melanie Taylor, Carey Tierney, Suzanne Wood, Anne Zak, Olivier Zongo, Stephen Bonner, Keith Hugill, Jessica Jones, Steven Liggett, Evie Headlam, Nageswar Bandla, Minnie Gellamucho, Michelle Davies, Christopher Thompson, Marwa Abdelrazik, Dhanalakshmi Bakthavatsalam, Munzir Elhassan, Arunkumar Ganesan, Anne Haldeos, Jeronimo Moreno-Cuesta, Dharam Purohit, Rachel Vincent, Kugan Xavier, Kumar Rohit, Frater Alasdair, Malik Saleem, Carter David, Jenkins Samuel, Zoe Lamond, Wall Alanna, Jaime Fernandez-Roman, David O. Hamilton, Emily Johnson, Brian Johnston, Maria Lopez Martinez, Suleman Mulla, David Shaw, Alicia A.C. Waite, Victoria Waugh, Ingeborg D. Welters, Karen Williams, Anna Cavazza, Maeve Cockrell, Eleanor Corcoran, Maria Depante, Clare Finney, Ellen Jerome, Mark McPhail, Monalisa Nayak, Harriet Noble, Kevin O'Reilly, Evita Pappa, Rohit Saha, Sian Saha, John Smith, Abigail Knighton, David Antcliffe, Dorota Banach, Stephen Brett, Phoebe Coghlan, Ziortza Fernandez, Anthony Gordon, Roceld Rojo, Sonia Sousa Arias, Maie Templeton, Megan Meredith, Lucy Morris, Lucy Ryan, Amy Clark, Julia Sampson, Cecilia Peters, Martin Dent, Margaret Langley, Saima Ashraf, Shuying Wei, Angela Andrew, Archana Bashyal, Neil Davidson, Paula Hutton, Stuart McKechnie, Jean Wilson, David Baptista, Rebecca Crowe, Rita Fernandes, Rosaleen Herdman-Grant, Anna Joseph, Denise O'Connor, Meryem Allen, Adam Loveridge, India McKenley, Eriko Morino, Andres Naranjo, Richard Simms, Kathryn Sollesta, Andrew Swain, Harish Venkatesh, Jacyntha Khera, Jonathan Fox, Gillian Andrew, Lucy Barclay, Marie Callaghan, Rachael Campbell, Sarah Clark, Dave Hope, Lucy Marshall, Corrienne McCulloch, Kate Briton, Jo Singleton, Sohphie Birch, Lutece Brimfield, Zoe Daly, David Pogson, Steve Rose, Ceri Battle, Elaine Brinkworth, Rachel Harford, Carl Murphy, Luke Newey, Tabitha Rees, Marie Williams, Sophie Arnold, Petra Polgarova, Katerina Stroud, Eoghan Meaney, Megan Jones, Anthony Ng, Shruti Agrawal, Nazima Pathan, Deborah White, Esther Daubney, Kay Elston, Lina Grauslyte, Musarat Hussain, Mandeep Phull, Tatiana Pogreban, Lace Rosaroso, Erika Salciute, George Franke, Joanna Wong, Aparna George, Laura Ortiz-Ruiz de Gordoa, Emily Peasgood, Claire Phillips, Michelle Bates, Jo Dasgin, Jaspret Gill, Annette Nilsson, James Scriven, Carlos Castro Delgado, Deborah Dawson, Lijun Ding, Georgia Durrant, Obiageri Ezeobu, Sarah Farnell-Ward, Abiola Harrison, Rebecca Kanu, Susannah Leaver, Elena Maccacari, Soumendu Manna, Romina Pepermans Saluzzio, Joana Queiroz, Tinashe Samakomva, Christine Sicat, Joana Texeira, Edna Fernandes Da Gloria, Ana Lisboa, John Rawlins, Jisha Mathew, Ashley Kinch, William James Hurt, Nirav Shah, Victoria Clark, Maria Thanasi, Nikki Yun, Kamal Patel, Sara Bennett, Emma Goodwin, Matthew Jackson, Alissa Kent, Clare Tibke, Wiesia Woodyatt, Ahmed Zaki, Azmerelda Abraheem, Peter Bamford, Kathryn Cawley, Charlie Dunmore, Maria Faulkner, Rumanah Girach, Helen Jeffrey, Rhianna Jones, Emily London, Imrun Nagra, Farah Nasir, Hannah Sainsbury, Clare Smedley, Tahera Patel, Matthew Smith, Srikanth Chukkambotla, Aayesha Kazi, Janice Hartley, Joseph Dykes, Muhammad Hijazi, Sarah Keith, Meherunnisa Khan, Janet Ryan-Smith, Philippa Springle, Jacqueline Thomas, Nick Truman, Samuel Saad, Dabheoc Coleman, Christopher Fine, Roseanna Matt, Bethan Gay, Jack Dalziel, Syamlan Ali, Drew Goodchild, Rhiannan Harling, Ravi Bhatterjee, Wendy Goddard, Chloe Davison, Stephen Duberly, Jeanette Hargreaves, Rachel Bolton, Miriam Davey, David Golden, Rebecca Seaman, Shiney Cherian, Sean Cutler, Anne Emma Heron, Anna Roynon-Reed, Tamas Szakmany, Gemma Williams, Owen Richards, Yusuf Cheema, Hollie Brooke, Sarah Buckley, Jose Cebrian Suarez, Ruth Charlesworth, Karen Hansson, John Norris, Alice Poole, Alastair Rose, Rajdeep Sandhu, Brendan Sloan, Elizabeth Smithson, Muthu Thirumaran, Veronica Wagstaff, Alexandra Metcalfe, Mark Brunton, Jess Caterson, Holly Coles, Matthew Frise, Sabi Gurung Rai, Nicola Jacques, Liza Keating, Emma Tilney, Shauna Bartley, Parminder Bhuie, Sian Gibson, Amanda Lyle, Fiona McNeela, Jayachandran Radhakrishnan, Alistair Hughes, Bryan Yates, Jessica Reynolds, Helen Campbell, Maria Thompsom, Steve Dodds, Stacey Duffy, Sandra Greer, Karen Shuker, Ascanio Tridente, Reena Khade, Ashok Sundar, George Tsinaslanidis, Isobel Birkinshaw, Joseph Carter, Kate Howard, Joanne Ingham, Rosie Joy, Harriet Pearson, Samantha Roche, Zoe Scott, Hollie Bancroft, Mary Bellamy, Margaret Carmody, Jacqueline Daglish, Faye Moore, Joanne Rhodes, Mirriam Sangombe, Salma Kadiri, Maria Croft, Ian White, Victoria Frost, Maia Aquino, Rajeev Jha, Vinodh Krishnamurthy, Lai Lim, Li Lim, Edward Combes, Teishel Joefield, Sonja Monnery, Valerie Beech, Sallyanne Trotman, Christine Almaden-Boyle, Pauline Austin, Louise Cabrelli, Stephen Cole, Matt Casey, Susan Chapman, Clare Whyte, Yolanda Baird, Aaron Butler, Indra Chadbourn, Linda Folkes, Heather Fox, Amy Gardner, Raquel Gomez, Gillian Hobden, Luke Hodgson, Kirsten King, Michael Margarson, Tim Martindale, Emma Meadows, Dana Raynard, Yvette Thirlwall, David Helm, Jordi Margalef, Kristine Criste, Rebecca Cusack, Kim Golder, Hannah Golding, Oliver Jones, Samantha Leggett, Michelle Male, Martyna Marani, Kirsty Prager, Toran Williams, Belinda Roberts, Karen Salmon, Peter Anderson, Katie Archer, Karen Austin, Caroline Davis, Alison Durie, Olivia Kelsall, Jessica Thrush, Charlie Vigurs, Laura Wild, Hannah-Louise Wood, Helen Tranter, Alison Harrison, Nicholas Cowley, Michael McAlindon, Andrew Burtenshaw, Stephen Digby, Emma Low, Aled Morgan, Naiara Cother, Tobias Rankin, Sarah Clayton, Alex McCurdy, Cecilia Ahmed, Balvinder Baines, Sarah Clamp, Julie Colley, Risna Haq, Anne Hayes, Jonathan Hulme, Samia Hussain, Sibet Joseph, Rita Kumar, Zahira Maqsood, Manjit Purewal, Leonie Benham, Zena Bradshaw, Joanna Brown, Melanie Caswell, Jason Cupitt, Sarah Melling, Stephen Preston, Nicola Slawson, Emma Stoddard, Scott Warden, Bethan Deacon, Ceri Lynch, Carla Pothecary, Lisa Roche, Gwenllian Sera Howe, Jayaprakash Singh, Keri Turner, Hannah Ellis, Natalie Stroud, Jodie Hunt, Joy Dearden, Emma Dobson, Andy Drummond, Michelle Mulcahy, Sheila Munt, Grainne O'Connor, Jennifer Philbin, Chloe Rishton, Redmond Tully, Sarah Winnard, Susanne Cathcart, Katharine Duffy, Alex Puxty, Kathryn Puxty, Lynne Turner, Jane Ireland, Gary Semple, Kate Long, Simon Whiteley, Elizabeth Wilby, Bethan Ogg, Amanda Cowton, Andrea Kay, Melanie Kent, Kathryn Potts, Ami Wilkinson, Suzanne Campbell, Ellen Brown, Julie Melville, Jay Naisbitt, Rosane Joseph, Maria Lazo, Olivia Walton, Alan Neal, Peter Alexander, Schvearn Allen, Joanne Bradley-Potts, Craig Brantwood, Jasmine Egan, Timothy Felton, Grace Padden, Luke Ward, Stuart Moss, Susannah Glasgow, Lynn Abel, Michael Brett, Brian Digby, Lisa Gemmell, James Hornsby, Patrick MacGoey, Pauline O'Neil, Richard Price, Natalie Rodden, Kevin Rooney, Radha Sundaram, Nicola Thomson, Bridget Hopkins, Laura Thrasyvoulou, Heather Willis, Martyn Clark, Martina Coulding, Edward Jude, Jacqueline McCormick, Oliver Mercer, Darsh Potla, Hafiz Rehman, Heather Savill, Victoria Turner, Charlotte Downes, Kathleen Holding, Katie Riches, Mary Hilton, Mel Hayman, Deepak Subramanian, Priya Daniel, Oluronke Adanini, Nikhil Bhatia, Maines Msiska, Rebecca Collins, Ian Clement, Bijal Patel, A. Gulati, Carole Hays, K. Webster, Anne Hudson, Andrea Webster, Elaine Stephenson, Louise McCormack, Victoria Slater, Rachel Nixon, Helen Hanson, Maggie Fearby, Sinead Kelly, Victoria Bridgett, Philip Robinson, Julie Camsooksai, Charlotte Humphrey, Sarah Jenkins, Henrik Reschreiter, Beverley Wadams, Yasmin Death, Victoria Bastion, Daphene Clarke, Beena David, Harriet Kent, Rachel Lorusso, Gamu Lubimbi, Sophie Murdoch, Melchizedek Penacerrada, Alastair Thomas, Jennifer Valentine, Ana Vochin, Retno Wulandari, Brice Djeugam, Gillian Bell, Katy English, Amro Katary, Louise Wilcox, Michelle Bruce, Karen Connolly, Tracy Duncan, Helen T-Michael, Gabriella Lindergard, Samuel Hey, Claire Fox, Jordan Alfonso, Laura Jayne Durrans, Jacinta Guerin, Bethan Blackledge, Jade Harris, Martin Hruska, Ayaa Eltayeb, Thomas Lamb, Tracey Hodgkiss, Lisa Cooper, Joanne Rothwell, Angela Allan, Felicity Anderson, Callum Kaye, Jade Liew, Jasmine Medhora, Teresa Scott, Erin Trumper, Adriana Botello, Liana Lankester, Nikitas Nikitas, Colin Wells, Bethan Stowe, Kayleigh Spencer, Craig Brandwood, Lara Smith, Katie Birchall, Laurel Kolakaluri, Deborah Baines, Anila Sukumaran, Elena Apetri, Cathrine Basikolo, Laura Catlow, Bethan Charles, Paul Dark, Reece Doonan, Alice Harvey, Daniel Horner, Karen Knowles, Stephanie Lee, Diane Lomas, Chloe Lyons, Tracy Marsden, Danielle McLaughlan, Liam McMorrow, Jessica Pendlebury, Jane Perez, Maria Poulaka, Nicola Proudfoot, Melanie Slaughter, Kathryn Slevin, Vicky Thomas, Danielle Walker, Angiy Michael, Matthew Collis, Tracey Cosier, Gemma Millen, Neil Richardson, Natasha Schumacher, Heather Weston, James Rand, Nicola Baxter, Steven Henderson, Sophie Kennedy-Hay, Christopher McParland, Laura Rooney, Malcolm Sim, Gordan McCreath, Louise Akeroyd, Shereen Bano, Matt Bromley, Lucy Gurr, Tom Lawton, James Morgan, Kirsten Sellick, Deborah Warren, Brian Wilkinson, Janet McGowan, Camilla Ledgard, Amelia Stacey, Kate Pye, Ruth Bellwood, Michael Bentley, Jeremy Bewley, Zoe Garland, Lisa Grimmer, Bethany Gumbrill, Rebekah Johnson, Katie Sweet, Denise Webster, Georgia Efford, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Jocelyn Keshet-Price, Georgina Randell, Katie Stammers, Maria Bokhari, Vanessa Linnett, Rachael Lucas, Wendy McCormick, Jenny Ritzema, Amanda Sanderson, Helen Wild, Anthony Rostron, Alistair Roy, Lindsey Woods, Sarah Cornell, Fiona Wakinshaw, Kimberley Rogerson, Jordan Jarmain, Robert Parker, Amie Reddy, Ian Turner-Bone, Laura Wilding, Peter Harding, Caroline Abernathy, Louise Foster, Andrew Gratrix, Vicky Martinson, Priyai Parkinson, Elizabeth Stones, Llucia Carbral-Ortega, Georgia Bercades, David Brealey, Ingrid Hass, Niall MacCallum, Gladys Martir, Eamon Raith, Anna Reyes, Deborah Smyth, Letizia Zitter, Sarah Benyon, Suzie Marriott, Linda Park, Samantha Keenan, Elizabeth Gordon, Helen Quinn, Kizzy Baines, Lenka Cagova, Adama Fofano, Lucie Garner, Helen Holcombe, Sue Mepham, Alice Michael Mitchell, Lucy Mwaura, Krithivasan Praman, Alain Vuylsteke, Julie Zamikula, Bally Purewal, Vanessa Rivers, Stephanie Bell, Hayley Blakemore, Borislava Borislavova, Beverley Faulkner, Emma Gendall, Elizabeth Goff, Kati Hayes, Matt Thomas, Ruth Worner, Kerry Smith, Deanna Stephens, Louise Mew, Esther Mwaura, Richard Stewart, Felicity Williams, Lynn Wren, Sara-Beth Sutherland, Emily Bevan, Jane Martin, Dawn Trodd, Geoff Watson, Caroline Wrey Brown, Amy Collins, Waqas Khaliq, Estefania Treus Gude, Olugbenga Akinkugbe, Alasdair Bamford, Emily Beech, Holly Belfield, Michael Bell, Charlene Davies, Gareth A.L. Jones, Tara McHugh, Hamza Meghari, Lauran O'Neill, Mark J. Peters, Samiran Ray, Ana Luisa Tomas, Iona Burn, Geraldine Hambrook, Katarina Manso, Ruth Penn, Pradeep Shanmugasundaram, Julie Tebbutt, Danielle Thornton, Jade Cole, Rhys Davies, Donna Duffin, Helen Hill, Ben Player, Emma Thomas, Angharad Williams, Denise Griffin, Nycola Muchenje, Mcdonald Mupudzi, Richard Partridge, Jo-Anna Conyngham, Rachel Thomas, Mary Wright, Maria Alvarez Corral, Reni Jacob, Cathy Jones, Craig Denmade, Sarah Beavis, Katie Dale, Rachel Gascoyne, Joanne Hawes, Kelly Pritchard, Lesley Stevenson, Amanda Whileman, Patricia Doble, Joanne Hutter, Corinne Pawley, Charmaine Shovelton, Marius Vaida, Deborah Butcher, Susie O'Sullivan, Nicola Butterworth-Cowin, Norfaizan Ahmad, Joann Barker, Kris Bauchmuller, Sarah Bird, Kay Cawthron, Kate Harrington, Yvonne Jackson, Faith Kibutu, Becky Lenagh, Shamiso Masuko, Gary H. Mills, Ajay Raithatha, Matthew Wiles, Jayne Willson, Helen Newell, Alison Lye, Lorenza Nwafor, Claire Jarman, Sarah Rowland-Jones, David Foote, Joby Cole, Roger Thompson, James Watson, Lisa Hesseldon, Irene Macharia, Luke Chetam, Jacqui Smith, Amber Ford, Samantha Anderson, Kathryn Birchall, Kay Housley, Sara Walker, Leanne Milner, Helena Hanratty, Helen Trower, Patrick Phillips, Simon Oxspring, Ben Donne, Catherine Jardine, Dewi Williams, Alasdair Hay, Rebecca Flanagan, Gareth Hughes, Scott Latham, Emma McKenna, Jennifer Anderson, Robert Hull, Kat Rhead, Carina Cruz, Natalie Pattison, Rob Charnock, Denise McFarland, Denise Cosgrove, Ashar Ahmed, Anna Morris, Srinivas Jakkula, Asifa Ali, Megan Brady, Sam Dale, Annalisa Dance, Lisa Gledhill, Jill Greig, Kathryn Hanson, Kelly Holdroyd, Marie Home, Diane Kelly, Ross Kitson, Lear Matapure, Deborah Melia, Samantha Mellor, Tonicha Nortcliffe, Jez Pinnell, Matthew Robinson, Lisa Shaw, Ryan Shaw, Lesley Thomis, Alison Wilson, Tracy Wood, Lee-Ann Bayo, Ekta Merwaha, Tahira Ishaq, Sarah Hanley, Meg Hibbert, Dariusz Tetla, Chrsitopher Woodford, Latha Durga, Gareth Kennard-Holden, Debbie Branney, Jordan Frankham, Sally Pitts, Nigel White, Shondipon Laha, Mark Verlander, Alexandra Williams, Abdelhakim Altabaibeh, Ana Alvaro, Kayleigh Gilbert, Louise Ma, Loreta Mostoles, Chetan Parmar, Kathryn Simpson, Champa Jetha, Lauren Booker, Anezka Pratley, Colene Adams, Anita Agasou, Tracie Arden, Amy Bowes, Pauline Boyle, Mandy Beekes, Heather Button, Nigel Capps, Mandy Carnahan, Anne Carter, Danielle Childs, Denise Donaldson, Kelly Hard, Fran Hurford, Yasmin Hussain, Ayesha Javaid, James Jones, Sanal Jose, Michael Leigh, Terry Martin, Helen Millward, Nichola Motherwell, Rachel Rikunenko, Jo Stickley, Julie Summers, Louise Ting, Helen Tivenan, Louise Tonks, Rebecca Wilcox, Maureen Holland, Natalie Keenan, Marc Lyons, Helen Wassall, Chris Marsh, Mervin Mahenthran, Emma Carter, Thomas Kong, Helen Blackman, Ben Creagh-Brown, Sinead Donlon, Natalia Michalak-Glinska, Sheila Mtuwa, Veronika Pristopan, Armorel Salberg, Eleanor Smith, Sarah Stone, Charles Piercy, Jerik Verula, Dorota Burda, Rugia Montaser, Lesley Harden, Irving Mayangao, Cheryl Marriott, Paul Bradley, Celia Harris, Susan Anderson, Eleanor Andrews, Janine Birch, Emma Collins, Kate Hammerton, Ryan O'Leary, Michele Clark, Sarah Purvis, Russell Barber, Claire Hewitt, Annette Hilldrith, Karen Jackson-Lawrence, Sarah Shepardson, Maryanne Wills, Susan Butler, Silvia Tavares, Amy Cunningham, Julia Hindale, Sarwat Arif, Sarah Bean, Karen Burt, Michael Spivey, Carrie Demetriou, Charlotte Eckbad, Sarah Hierons, Lucy Howie, Sarah Mitchard, Lidia Ramos, Alfredo Serrano-Ruiz, Katie White, Fiona Kelly, Daniele Cristiano, Natalie Dormand, Zohreh Farzad, Mahitha Gummadi, Kamal Liyanage, Brijesh Patel, Sara Salmi, Geraldine Sloane, Vicky Thwaites, Mathew Varghese, Anelise C. Zborowski, John Allan, Tim Geary, Gordon Houston, Alistair Meikle, Peter O'Brien, Miranda Forsey, Agilan Kaliappan, Anne Nicholson, Joanne Riches, Mark Vertue, Elizabeth Allan, Kate Darlington, Ffyon Davies, Jack Easton, Sumit Kumar, Richard Lean, Daniel Menzies, Richard Pugh, Xinyi Qiu, Llinos Davies, Hannah Williams, Jeremy Scanlon, Gwyneth Davies, Callum Mackay, Joannne Lewis, Stephanie Rees, Metod Oblak, Monica Popescu, Mini Thankachen, Andrew Higham, Kerry Simpson, Jayne Craig, Rosie Baruah, Sheila Morris, Susie Ferguson, Amy Shepherd, Luke Stephen Prockter Moore, Marcela Paola Vizcaychipi, Laura Gomes de Almeida Martins, Jaime Carungcong, Inthakab Ali Mohamed Ali, Karen Beaumont, Mark Blunt, Zoe Coton, Hollie Curgenven, Mohamed Elsaadany, Kay Fernandes, Sameena Mohamed Ally, Harini Rangarajan, Varun Sarathy, Sivarupan Selvanayagam, Dave Vedage, Matthew White, Mandy Gill, Paul Paul, Valli Ratnam, Sarah Shelton, Inez Wynter, Siobhain Carmody, Valerie Joan Page, Claire Marie Beith, Karen Black, Suzanne Clements, Alan Morrison, Dominic Strachan, Margaret Taylor, Michelle Clarkson, Stuart D'Sylva, Kathryn Norman, Fiona Auld, Joanne Donnachie, Ian Edmond, Lynn Prentice, Nikole Runciman, Dario Salutous, Lesley Symon, Anne Todd, Patricia Turner, Abigail Short, Laura Sweeney, Euan Murdoch, Dhaneesha Senaratne, Michaela Hill, Thogulava Kannan, Wild Laura, Rikki Crawley, Abigail Crew, Mishell Cunningham, Allison Daniels, Laura Harrison, Susan Hope, Ken Inweregbu, Sian Jones, Nicola Lancaster, Jamie Matthews, Alice Nicholson, Gemma Wray, Helen Langton, Rachel Prout, Malcolm Watters, Catherine Novis, Anthony Barron, Ciara Collins, Sundeep Kaul, Heather Passmore, Claire Prendergast, Anna Reed, Paula Rogers, Rajvinder Shokkar, Meriel Woodruff, Hayley Middleton, Oliver Polgar, Claire Nolan, Kanta Mahay, Dawn Collier, Anil Hormis, Victoria Maynard, Cheryl Graham, Rachel Walker, Ellen Knights, Alicia Price, Alice Thomas, Chris Thorpe, Teresa Behan, Caroline Burnett, Jonathan Hatton, Elaine Heeney, Atideb Mitra, Maria Newton, Rachel Pollard, Rachael Stead, Vishal Amin, Elena Anastasescu, Vikram Anumakonda, Komala Karthik, Rizwana Kausar, Karen Reid, Jacqueline Smith, Janet Imeson-Wood, Denise Skinner, Jane Gaylard, Dee Mullan, Julie Newman, Alison Brown, Vikki Crickmore, Gabor Debreceni, Joy Wilkins, Liz Nicol, Rosie Reece-Anthony, Mark Birt, Alison Ghosh, Emma Williams, Louise Allen, Eva Beranova, Nikki Crisp, Joanne Deery, Tracy Hazelton, Alicia Knight, Carly Price, Sorrell Tilbey, Salah Turki, Sharon Turney, Joshua Cooper, Cheryl Finch, Sarah Liderth, Alison Quinn, Natalia Waddington, Tina Coventry, Susan Fowler, Michael MacMahon, Amanda McGregor, Anne Cowley, Judith Highgate, Jane Gregory, Susan O'Connell, Tim Smith, Luigi Barberis, Shameer Gopal, Nichola Harris, Victoria Lake, Stella Metherell, Elizabeth Radford, Amelia Daniel, Joanne Finn, Rajnish Saha, Nikki White, Phil Donnison, Fiona Trim, Beena Eapen, Jenny Birch, Laura Bough, Josie Goodsell, Rebecca Tutton, Patricia Williams, Sarah Williams, Barbara Winter-Goodwin, Ailstair Nichol, Kathy Brickell, Michelle Smyth, Lorna Murphy, Samantha Coetzee, Alistair Gales, Igor Otahal, Meena Raj, Craig Sell, Paula Hilltout, Jayne Evitts, Amanda Tyler, Joanne Waldron, Kate Beesley, Sarah Board, Agnieszka Kubisz-Pudelko, Alison Lewis, Jess Perry, Lucy Pippard, Di Wood, Clare Buckley, Peter Barry, Neil Flint, Patel Rekha, Dawn Hales, Lara Bunni, Claire Jennings, Monica Latif, Rebecca Marshall, Gayathri Subramanian, Peter J. McGuigan, Christopher Wasson, Stephanie Finn, Jackie Green, Erin Collins, Bernadette King, Andy Campbell, Sara Smuts, Joseph Duffield, Oliver Smith, Lewis Mallon, Watkins Claire, Liam Botfield, Joanna Butler, Catherine Dexter, Jo Fletcher, Atul Garg, Aditya Kuravi, Poonam Ranga, Emma Virgilio, Zakaula Belagodu, Bridget Fuller, Anca Gherman, Olumide Olufuwa, Remi Paramsothy, Carmel Stuart, Naomi Oakley, Charlotte Kamundi, David Tyl, Katy Collins, Pedro Silva, June Taylor, Laura King, Charlotte Coates, Maria Crowley, Phillipa Wakefield, Jane Beadle, Laura Johnson, Janet Sargeant, Madeleine Anderson, Ailbhe Brady, Rebekah Chan, Jeff Little, Shane McIvor, Helena Prady, Helen Whittle, Bijoy Mathew, Ben Attwood, Penny Parsons, Geraldine Ward, Pamela Bremmer, West Joe, Baird Tracy, Ruddy Jim, Ellie Davies, Sonia Sathe, Catherine Dennis, Alastair McGregor, Victoria Parris, Sinduya Srikaran, Anisha Sukha, Noreen Clarke, Jonathan Whiteside, Mairi Mascarenhas, Avril Donaldson, Joanna Matheson, Fiona Barrett, Marianne O'Hara, Laura Okeefe, Clare Bradley, Christine Eastgate-Jackson, Helder Filipe, Daniel Martin, Amitaa Maharajh, Sara Mingo Garcia, Glykeria Pakou, Mark De Neef, Kathy Dent, Elizabeth Horsley, Muhmmad Nauman Akhtar, Sandra Pearson, Dorota Potoczna, Sue Spencer, Melanie Clapham, Rosemary Harper, Una Poultney, Polly Rice, Rachel Mutch, Lisa Armstrong, Hayley Bates, Emma Dooks, Fiona Farquhar, Brigid Hairsine, Chantal McParland, Sophie Packham, Rehana Bi, Barney Scholefield, Lydia Ashton, Linsha George, Sophie Twiss, David Wright, Manish Chablani, Amy Kirkby, Kimberley Netherton, Kim Davies, Linda O'Brien, Zohra Omar, Emma Perkins, Tracy Lewis, Isobel Sutherland, Karen Burns, Dr Ben Chandler, Kerry Elliott, Janine Mallinson, Alison Turnbull, Prisca Gondo, Bernard Hadebe, Abdul Kayani, Bridgett Masunda, Taya Anderson, Dan Hawcutt, Laura O'Malley, Laura Rad, Naomi Rogers, Paula Saunderson, Kathryn Sian Allison, Deborah Afolabi, Jennifer Whitbread, Dawn Jones, Rachael Dore, Matthew Halkes, Pauline Mercer, Lorraine Thornton, Joy Dawson, Sweyn Garrioch, Melanie Tolson, Jonathan Aldridge, Ritoo Kapoor, David Loader, Karen Castle, Sally Humphreys, Ruth Tampsett, Katherine Mackintosh, Amanda Ayers, Wendy Harrison, Julie North, Suzanne Allibone, Roman Genetu, Vidya Kasipandian, Amit Patel, Ainhi Mac, Anthony Murphy, Parisa Mahjoob, Roonak Nazari, Lucy Worsley, Andrew Fagan, Thomas Bemand, Ethel Black, Arnold Dela Rosa, Ryan Howle, Shaman Jhanji, Ravishankar Rao Baikady, Kate Colette Tatham, Benjamin Thomas, Dina Bell, Rosalind Boyle, Katie Douglas, Lynn Glass, Emma Lee, Liz Lennon, Austin Rattray, Abigail Taylor, Rachel Anne Hughes, Helen Thomas, Alun Rees, Michaela Duskova, Janet Phipps, Suzanne Brooks, Michelle Edwards, Sheena Quaid, Ekaterina Watson, Adam Brayne, Emma Fisher, Jane Hunt, Peter Jackson, Duncan Kaye, Nicholas Love, Juliet Parkin, Victoria Tuckey, Lynne Van Koutrik, Sasha Carter, Benedict Andrew, Louise Findlay, Katie Adams, Jen Service, Alison Williams, Claire Cheyne, Anne Saunderson, Sam Moultrie, Miranda Odam, Kathryn Hall, Isheunesu Mapfunde, Charlotte Willis, Alex Lyon, Chunda Sri-Chandana, Joslan Scherewode, Lorraine Stephenson, Sarah Marsh, John Hardy, Henry Houlden, Eleanor Moncur, Ambreen Tariq, Arianna Tucci, Maria Hobrok, Ronda Loosley, Heather McGuinness, Helen Tench, Rebecca Wolf-Roberts, Val Irvine, Benjamin Shelley, Claire Gorman, Abhinav Gupta, Elizabeth Timlick, Rebecca Brady, Barry Milligan, Arianna Bellini, Jade Bryant, Anton Mayer, Amy Pickard, Nicholas Roe, Jason Sowter, Alex Howlett, Katy Fidler, Emma Tagliavini, and Kevin Donnelly

Subjects
SARS-CoV-2, host genetics, toll-like receptor 7, targeted sequencing, rare variants, variant collapsing analysis, Genetics, QH426-470
Abstract

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Published
2024
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38. Copy number variation and population-specific immune genes in the model vertebrate zebrafish

Author

Yannick Schäfer, Katja Palitzsch, Maria Leptin, Andrew R Whiteley, Thomas Wiehe, and Jaanus Suurväli

Subjects
Danio rerio, NLR, copy number variation, NOD-like receptor, immune genes, PacBio, Medicine, Science, Biology (General), QH301-705.5
Abstract

Copy number variation in large gene families is well characterized for plant resistance genes, but similar studies are rare in animals. The zebrafish (Danio rerio) has hundreds of NLR immune genes, making this species ideal for studying this phenomenon. By sequencing 93 zebrafish from multiple wild and laboratory populations, we identified a total of 1513 NLRs, many more than the previously known 400. Approximately half of those are present in all wild populations, but only 4% were found in 80% or more of the individual fish. Wild fish have up to two times as many NLRs per individual and up to four times as many NLRs per population than laboratory strains. In contrast to the massive variability of gene copies, nucleotide diversity in zebrafish NLR genes is very low: around half of the copies are monomorphic and the remaining ones have very few polymorphisms, likely a signature of purifying selection.

Published
2024
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39. A qualitative study evaluating COVID-19 vaccine hesitancy among individuals living in Mississippi

Author

Avery Leigland, Trisha Arnold, Kayla K. Giorlando, Andrew P. Barnett, Courtney E. Sims-Gomillia, Zoe Bertone, Precious Patrick Edet, Laura Whiteley, and Larry K. Brown

Subjects
COVID-19, Vaccine hesitancy, Vaccination, Mississippi, Qualitative, Public aspects of medicine, RA1-1270
Abstract

Background: COVID-19 vaccination rates are lower in the Southern United States compared to other regions. This study investigated COVID-19 vaccination hesitancy in Mississippi (MS) to identify preferences that may boost MS vaccination strategies in areas with poor vaccine uptake. Methods: Qualitative interviews were completed between April 2021 and January 2022 with staff and patients at four Federally Qualified Health Centers in MS. Interviews included the following COVID-19 vaccine topics: willingness to be vaccinated, barriers and facilitators, and methods for providing vaccine information. Data were organized with NVivo software and analyzed using reflexive thematic analysis. Results: Fifteen clinic staff and 49 patients were interviewed. Barriers to vaccine uptake included a lack of knowledge and understanding of how the vaccine worked, distrust of the government, fear of side effects, and social pressure to stay unvaccinated. Vaccination facilitators included its widespread accessibility, a desire to protect themselves and vulnerable populations, and a previous unpleasant COVID-19 illness experience. Participants stated that vaccine information should be provided by health organizations and familiar, respected community members. Conclusions: Results identified barriers to vaccination, such as mistrust of the government and healthcare system, and facilitators like vaccination advocacy originating from congregations and religious leaders. These findings can inform future COVID-19 vaccination efforts to increase overall immunization rates in MS. Future research in other locations could further assess commonalities and differences in the barriers and facilitators to vaccination.

Published
2024
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40. Quadriceps and Hamstrings Activation Peaks Earlier as Athletes Repeatedly Hop, but There are Differences Depending on ACL Reconstruction Technique.

Author

Einar Einarsson, Olivia Barbosa, Magnus Kjartan Gislason, Kristin Briem, Argyro Kotsifaki, and Rodney Whiteley

Subjects
Sports medicine, RC1200-1245
Abstract

# Background After Anterior Cruciate Ligament Reconstruction (ACLR) athletes face the challenge of regaining their previous competitive level while avoiding re-injury and early knee joint cartilage degeneration. Quadriceps and hamstrings strength reductions and neuromuscular alterations potentially related to risk of re-injury are present after ACLR and relate to deficits in muscle activation. # Design Cross-sectional laboratory study # Purpose To examine quadriceps and hamstrings muscle activation during repeated hops in healthy pivoting-sport athletes and those who had undergone ACLR (bone-tendon-bone and semitendinosus graft) who had met functional criteria allowing return to training. # Methods Surface electromyography (SEMG) was recorded from vastus medialis and lateralis and medial and lateral hamstrings bilaterally during 30 seconds' repeated hopping in male athletes on average eight months after ACLR surgery (5-12 months). All patients underwent hamstring (HS) (n=24) or bone-tendon-bone (BTB) reconstruction (n=20) and were compared to healthy controls (n=31). The SEMG signals were normalized to those obtained during maximal voluntary isometric contraction. # Results A significant time shift in peak muscle activation (earlier) was seen for: vastus medialis and vastus lateralis activation in the control group, in the BTB group's healthy (but not injured) leg and both legs of the HS group. A significant time shift in peak muscle activation was seen for lateral hamstrings (earlier) in all but the BTB group's injured leg and the medial hamstrings in the control group only. Lower peak activation levels of the vastus lateralis (p\

Published
2024
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41. Characterization of a new Pseudomonas aeruginosa Queuovirinae bacteriophage

Author

Lauren E. Whiteley and Marvin Whiteley

Subjects
Pseudomonas aeruginosa, bacteriophage, Queuovirinae, pili, Microbiology, QR1-502
Abstract

ABSTRACTThe ESKAPEE pathogen Pseudomonas aeruginosa is a common cause of chronic wound and cystic fibrosis lung infections, as well as acute burn and nosocomial infections. Many of these infections are recalcitrant to conventional antibiotic therapies due to both traditional antibiotic resistance mechanisms and antimicrobial tolerance. Recent successes with bacteriophage (phage) therapy to treat chronic human P. aeruginosa infections have led to a renewed interest in isolating and characterizing new P. aeruginosa phages. Here, we isolated and characterized a new lytic phage (termed PIP, pili-infecting phage) capable of infecting P. aeruginosa PA14. PIP is a tailed phage with an icosahedral head and flexible tail containing a genome that is 57,462 bp in length. Phylogenetic analysis reveals that PIP belongs to the subfamily Queuovirinae and genus Nipunavirus but is highly divergent in gene content from known Nipunaviruses. By isolating and characterizing a P. aeruginosa strain that spontaneously evolved resistance to PIP, we show that the receptor for PIP is Type IV pili. In summary, we isolated a new P. aeruginosa phage species with a unique genome, thus increasing the diversity of phages known to infect this important human pathogen.IMPORTANCEThe opportunistic pathogen Pseudomonas aeruginosa causes both acute and chronic human infections. These infections are notoriously difficult to treat due to both antibiotic resistance and antibiotic tolerance. The increasing frequency of antibiotic failure in P. aeruginosa infections has led scientists to explore other treatment options, including bacteriophage (phage) therapy. To this end, there has been a significant effort to identify new Pseudomonas phages. Here, we isolated and characterized a bacteriophage (termed PIP, pili-infecting phage) that infects P. aeruginosa PA14. Examination of the PIP genome revealed that this phage represents a new species in the subclass Queuovirinae. The isolation and characterization of spontaneous PA14 mutants that are resistant to PIP infection revealed Type IV pili as the PIP receptor. Ultimately, this study characterizes a new species of Pseudomonas phage, thus enhancing the known diversity of phages that infect this important pathogen.

Published
2024
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42. Automated Clinical Coding: What, Why, and Where We Are?

Author

Dong, Hang, Falis, Matúš, Whiteley, William, Alex, Beatrice, Matterson, Joshua, Ji, Shaoxiong, Chen, Jiaoyan, and Wu, Honghan

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence, 68T07 (Primary), 68T50 (Secondary), I.2.7, J.3
Abstract

Clinical coding is the task of transforming medical information in a patient's health records into structured codes so that they can be used for statistical analysis. This is a cognitive and time-consuming task that follows a standard process in order to achieve a high level of consistency. Clinical coding could potentially be supported by an automated system to improve the efficiency and accuracy of the process. We introduce the idea of automated clinical coding and summarise its challenges from the perspective of Artificial Intelligence (AI) and Natural Language Processing (NLP), based on the literature, our project experience over the past two and half years (late 2019 - early 2022), and discussions with clinical coding experts in Scotland and the UK. Our research reveals the gaps between the current deep learning-based approach applied to clinical coding and the need for explainability and consistency in real-world practice. Knowledge-based methods that represent and reason the standard, explainable process of a task may need to be incorporated into deep learning-based methods for clinical coding. Automated clinical coding is a promising task for AI, despite the technical and organisational challenges. Coders are needed to be involved in the development process. There is much to achieve to develop and deploy an AI-based automated system to support coding in the next five years and beyond., Comment: accepted for npj Digital Medicine

Published
2022

44. Prospective predictors of care partner burden and depression in Parkinson's disease

Author

Whiteley, Nicole, Pluim, Celina F, Split, Molly, Tuazon, Angelie Cabrera, Moore, Raeanne C, Litvan, Irene, Lessig, Stephanie, Filoteo, J Vincent, and Schiehser, Dawn M

Subjects
Aging, Neurosciences, Neurodegenerative, Behavioral and Social Science, Serious Mental Illness, Brain Disorders, Depression, Mental Health, Clinical Research, Parkinson's Disease, Management of diseases and conditions, 7.1 Individual care needs, Neurological, Good Health and Well Being, Aged, Caregivers, Humans, Parkinson Disease, Quality of Life, Surveys and Questionnaires, caregiver, caregiver outcomes, longitudinal, movement disorders, Clinical Sciences, Psychology, Cognitive Sciences, Geriatrics, Clinical sciences, Health services and systems, Clinical and health psychology
Abstract

ObjectivesCare partners who provide informal care to individuals with Parkinson's disease (PD) report higher levels of burden and depression; however, longitudinal research on these symptoms is scarce. The current study assessed changes in care partner burden and depression, and patient and care partner predictors of these symptoms over time. Such knowledge may provide important information for assessment and treatment of depression and burden in care partners of individuals with PD.Research design and methodsParticipants were 88 PD patients without dementia and their self-identified care partner (n = 88). Care partners completed the Geriatric Depression Scale and Zarit Burden Interview. PD participants completed mood questionnaires and a motor exam at baseline and 2 year follow-up. Relationships among care partner burden and depression over time with patient and care partner predictors (i.e., demographic, mood, and disease characteristics) were assessed using correlations and regression analyses.ResultsCare partner burden and depression significantly increased over an approximate 2 year period. Greater baseline disease severity predicted worsening of care partner burden (p = 0.028), while baseline patient depression predicted worsening of care partner depression (p = 0.002).ConclusionsResults highlight differential impacts of specific PD symptoms on worsening care partner burden compared to depression; increased PD disease severity predicts increased burden, while patient mood predicts worsening of depression over time. Targeting PD disease severity and mood symptoms may prevent the progression of care partner burden and depression.

Published
2022

45. A mixed-methods process evaluation of the feasibility and acceptability of involving community and peer role models within a physical activity intervention for primary-school-aged girls (the CHARMING study)

Author

Kelly Morgan, Jordan Van Godwin, Rebecca Cannings-John, Britt Hallingberg, Graham Moore, Bethan Pell, Holly Whiteley, and Jemma Hawkins

Subjects
Physical activity, Intervention, School, Role models, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Role models have been identified as a potential means to tackle the persisting low levels of physical activity among young girls. The aim of this research was to explore the involvement of community- and peer role models within the CHARMING (CHoosing Active Role Models to INspire Girls) intervention, an intervention which aims to increase and sustain physical activity among 9–10-year-old girls. The research questions were, is it feasible and acceptable to recruit role models? and what are the perceived barriers and facilitators to the inclusion of peer role models within the intervention? Methods A mixed methods process evaluation was embedded within a larger feasibility study, involving three secondary schools and four adjoining primary schools in South Wales, United Kingdom. One-to-one interviews were conducted with teachers (N = 10) across the seven schools and community role models (N = 10). Focus groups were conducted with 18 peer role models (older girls from adjoining secondary schools) and 18 girls aged 9–10-years who had participated in the intervention. Primary school teachers kept observation logs of each intervention session. A researcher completed observation logs of two random sessions per school. Qualitative data were analysed using thematic analysis with a combined deductive and inductive coding approach. Observation data were analysed using descriptive statistics. Data were triangulated and comparative analyses conducted across schools. Results Twenty-three peer role models (aged 12–16-years) and 16 community role models participated in intervention delivery. Overall, the inclusion of both types of role models was shown as acceptable and feasible within the CHARMING intervention. Observation data highlighted key areas (i.e., intervention components delivered inconsistently) for further qualitative exploration. Six themes were identified during analyses; reach and access, communication, logistics, existing systems, interpersonal relationships, and perceived impacts. Themes were intertwined across the barriers and facilitators of recruitment and implementation. Areas for future improvement were highlighted. Conclusions Findings can be used to optimise the CHARMING intervention and inform wider interventions or policies employing several role models across settings to promote physical activity among children.

Published
2023
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46. Magnetic Resonance Elastography for Staging Liver Fibrosis in the Oncopig

Author

Ron C. Gaba, Lobna Elkhadragy, Thomas Pennix, Kyle M. Schachtschneider, Courtni R. Bolt, Aaron Anderson, Shreyan Majumdar, Denise Weber, Herbert E. Whiteley, Daniel P. Regan, Lawrence B. Schook, and Bradley P. Sutton

Subjects
swine, liver, fibrosis, liver cirrhosis, magnetic resonance imaging, Medicine (General), R5-920
Abstract

This pilot study investigated the feasibility of using magnetic resonance elastography (MRE) for the non-invasive detection and quantification of liver fibrosis in the Oncopig cancer model. Seven 8-week-old Oncopigs underwent alcoholic liver fibrosis induction and serial MRE imaging and liver biopsy at 1, 2, and 3 months post procedure. MRE was utilized to quantify liver stiffness, and liver fibrosis was histologically graded using the METAVIR system. The primary outcome measure was the capability to detect and quantify liver fibrosis using MRE with radiologic–pathologic correlation. Liver fibrosis induction, MRE imaging, and liver biopsy were successfully performed. MRE liver fibrosis was evident in 57% (4/7), 50% (3/6), and 40% (2/5) animal subjects 1, 2, and 3 months after fibrosis induction, with mean liver stiffness of 2.94, 3.25, and 2.91 kPa, respectively. Histological liver fibrosis was noted in 71% (5/7), 100% (5/5), and 100% (5/5) of animal subjects with available tissue samples. There was no significant statistical correlation between the MRE-measured liver stiffness and the METAVIR fibrosis scores. In conclusion, quantifiable liver fibrosis may be induced in the Oncopig. MRE has potential utility in non-invasively detecting liver stiffness in this large-animal preclinical model, though tissue biopsy was more sensitive in demonstrating disease.

Published
2024
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48. BID expression determines the apoptotic fate of cancer cells after abrogation of the spindle assembly checkpoint by AURKB or TTK inhibitors

Author

Bertran-Alamillo, Jordi, Giménez-Capitán, Ana, Román, Ruth, Talbot, Sara, Whiteley, Rebecca, Floc’h, Nicolas, Martínez-Pérez, Elizabeth, Martin, Matthew J., Smith, Paul D., Sullivan, Ivana, Terp, Mikkel G., Saeh, Jamal, Marino-Buslje, Cristina, Fabbri, Giulia, Guo, Grace, Xu, Man, Tornador, Cristian, Aguilar-Hernández, Andrés, Reguart, Noemí, Ditzel, Henrik J., Martínez-Bueno, Alejandro, Nabau-Moretó, Núria, Gascó, Amaya, Rosell, Rafael, Pease, J. Elizabeth, Polanska, Urszula M., Travers, Jon, Urosevic, Jelena, and Molina-Vila, Miguel A.

Published
2023
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49. Accuracy of diagnostic tests in cardiac injury after blunt chest trauma: a systematic review and meta-analysis

Author

Kyriazidis, Ioannis Panagiotis, Jakob, Dominik A., Vargas, Juliana Alexandra Hernández, Franco, Oscar H., Degiannis, Elias, Dorn, Patrick, Pouwels, Sjaak, Patel, Bijendra, Johnson, Ian, Houdlen, Christopher John, Whiteley, Graham S., Head, Marion, Lala, Anil, Mumtaz, Haroon, Soler, J. Agustin, Mellor, Katie, Rawaf, David, Ahmed, Ahmed R., Ahmad, Suhaib J. S., and Exadaktylos, Aristomenis

Published
2023
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50. Harmonising electronic health records for reproducible research: challenges, solutions and recommendations from a UK-wide COVID-19 research collaboration

Author

Abbasizanjani, Hoda, Torabi, Fatemeh, Bedston, Stuart, Bolton, Thomas, Davies, Gareth, Denaxas, Spiros, Griffiths, Rowena, Herbert, Laura, Hollings, Sam, Keene, Spencer, Khunti, Kamlesh, Lowthian, Emily, Lyons, Jane, Mizani, Mehrdad A., Nolan, John, Sudlow, Cathie, Walker, Venexia, Whiteley, William, Wood, Angela, and Akbari, Ashley

Published
2023
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